Female Non-smokers Research Articles

P59.04 Sex-Related Differences in Genomic and Immune Profiling of Lung Adenocarcinoma

The responses to therapeutic treatment can be finely tuned by sex-related cellular and/or molecular biology. Such sex determination for the disease onset and progression has been recognized in many tumor types. However, the sex disparities in genomic and immune profiles of lung adenocarcinoma (LUAD) remain poorly understood. The aim of this study is to explore the sex-associated biases in mutation and immune portrait across Asian and non-Asian LUADs. DNA sequencing (n=305) and mRNA expression profiles (n=172) of Asian LUADs are downloaded from OncoSG together with related clinical records. To assess possible interaction between sex and genetic background, the somatic mutational profiles (n=614) and mRNA expression profiles (n=425) of Non-Asian LUADs were also downloaded from The Cancer Genome Atlas. The relative abundance of different immune cells in tumor was determined using a method for deconvolving the cell composition of complex tissues from gene expression data. We then compared somatic mutation profiles and the abundance of tumor-infiltrating immune cells between male and female LUADs. Additionally, mRNA expression data from a Chinese CHOICE cohort (n=128 LUADs) were used to validate the sex-specific immune infiltrates deconvolved from OncoSG cohort. The major clinicopathological features of two cohorts are summarized in Figure 1. EGFR mutation was more frequent in smoker females than males across the two cohorts. While in non-smokers, EGFR mutation showed not significant gender disparities. A higher EGFR mutation frequency was observed in male non-smokers than smokers (P=0.004), regardless of ethnic origin. Interestingly, in the non-Asian cohort, EGFR mutation presented a significantly higher frequency in female non-smokers than female smokers (P<0.0001), but this divergence was not observed between Asian female smokers and non-smokers. Among smokers, EGFR mutation type in females can be described by the substitutions pointing out unique oncogenic etiologies including "UV light" (COSMIC Signature 7), “APOBEC” (Signature 2) and “Defective DNA MMR” (Signature 15), but not in males. While among non-smokers, “Smoking” signature (Signature 4) was preeminent in Asian males, but no in other subpopulations. Moreover, in silico analysis of cellular composition disclosed an increase of resting CD4 memory T cells and dendritic cells in Asian females compared to males. Additionally, Macrophages M2 were more abundant in Asian males compared to females. Our findings provided evidence that sex-related molecular and cellular components are involved in shaping tumor distinct genomic and immune features, which might have important impact on personalized targeted and immune therapy. Further research is warranted to identify the molecular mechanisms underlying sex-related differences.

Effect of age and gender in non-smokers with oral squamous cell carcinoma: Multi-institutional study

BackgroundIn developing countries, oral squamous cell carcinoma (OSCC) is predominantly a cancer affecting older males who smoke tobacco. In countries with effective public health strategies, smoking rates are declining rapidly. It is not clear if patients who develop OSCC without these traditional risk factors represent a clinically distinct cohort with different prognosis. A recent analysis found that elderly non-smoking females with OSCC had significantly worse prognosis, concluding that this was a distinct patient population with poorer survival. The primary aim of this study was to determine the effect of gender and age on prognosis in OSCC, and the interaction between these two variables. MethodsMultinational multi-institutional data were collected from six sites. The primary outcome of interest was disease specific survival (DSS). Time to local, regional, and distant recurrence were investigated as secondary outcomes. Results3379 patients with OSCC were included. Males had significantly worse DSS compared to females (HR 1.24, 95% CI 1.08–1.43, p = 0.003). Females <70 years of age had significantly better DSS compared to females ≥70 years of age (HR 0.69, 95% CI 0.51–0.94, p < 0.001) but elderly females had similar DSS to males, regardless of age. When age was divided into three groups, the middle-aged group (45–69 years) had a significantly better DSS compared to elderly patients (HR 0.87, 95%CI 0.78–0.96, p < 0.001), however younger patients had similar DSS to elderly patients. When the effect of age (young v middle v elderly) was compared in each gender, young and middle-aged females had the most favourable DSS (log-rank p < 0.001). Middle-aged females who smoked had a 10% survival advantage compared to middle-aged males that smoked at five years. ConclusionsAge, gender, tumour subsite, and smoking status are important drivers of survival in OSCC. However, gender appears to be the most important predictor with young and middle-aged females having the most favourable prognosis.

European Whites May Need Lower Minimum Therapeutic Clozapine Doses Than Those Customarily Proposed.

A nomogram from a British naturalistic study proposed that the clozapine dosing needed to reach a serum concentration of 350 ng/mL ranged from 265 mg/d (female nonsmokers) to 525 mg/d (male smokers). Some European reviews have used these dosing recommendations, which seem greater than what we found in an Italian White sample ranging from 245 mg/d (female nonsmokers) to 299 mg/d (male smokers). Five other published samples of European Whites were added to the Italian sample to estimate clozapine doses recommended for reaching 350 ng/mL. Average clozapine metabolizers were obtained by eliminating outliers with confounding variables: (1) psychiatric inducers and inhibitors; (2) doses less than 100 mg/d; and (3) when possible, patients with inflammation, obesity, or using oral contraceptives. The study included 1363 average metabolizer European Whites: the Italian sample and 5 new samples. Mean averages that reached serum concentration levels of 350 ng/mL were calculated after stratification by sex and smoking status in each sample. Then, weighted mean averages were obtained by combining the 6 samples. The estimated weighted mean clozapine dosages ranged from 236 to 368 mg/d (236 mg/d in 218 female nonsmokers, 256 mg/d in 340 male nonsmokers, 357 mg/d in 269 female smokers, and 368 mg/d in 546 male smokers). Our recommended dosages are less than those recommended in Europe. Future studies in European Whites need to replicate these recommended doses for average metabolizer patients after sex and smoking stratification and further explore clozapine dosing for those with relevant clinical confounders.

Acoustic and Auditory-Perceptual Analysis of Voice in the Female Smokers Who Do Not Have Self-Reported Voice Complaint

Smoking affects the voice quality and the previous studies presented higher Voice Handicap Index (VHI) scores, and abnormal acoustic data in smokers. However, there is no study revealing any voice parameter indicating incipient damage in voice functionality. The studies documented that the adverse effects of smoking on phonatory function were higher in females than males and further the prevalence of smoking among females tends to increase. The purpose of this study was to investigate the effect of smoking on the acoustic and auditory-perceptual analysis of the speaking voice in female smokers who scored the VHI-10 scale as grade 0 (absent), and thus to look for a criterion for incipient vocal damage of smoking. The study group composed of 22 female smokers and 22 female nonsmokers between the ages of 18 and 55 years. The acoustic parameters (mean F0, jitter local [%], jitter local abs, jitter rap, jitter ppq, shimmer local [%], shimmer local [dB], shimmer apq3, shimmer apq5, shimmer apq11, and mean HNR) and the GRBAS scale were analyzed in all subjects. No significant difference observed between the smoker and nonsmokers groups in acoustic voice analysis. It was seen that the smokers presented a small but significant increase in the Strain parameter of the GRBAS scale while there was no significant difference in the Grade, Roughness, Breathiness, and Asthenia parameters between the study groups. The results of this study indicate that increase in Strain could be considered as an early data in the smokers without voice complaints. However, our data declared that conventional acoustic perturbation analysis did not reveal incipient Strain in voice.

Prevalence and risk factors of post-operative nausea and vomiting in a tertiary-care hospital: A cross-sectional observational study

BackgroundPost-operative nausea and vomiting (PONV) is an unpleasant and one of the most distressing symptoms for any patient undergoing surgery. The anaesthetist is usually blamed, despite evidence that PONV results from a variety of factors including patient characteristics, anaesthetic techniques, and the type of surgery and post-operative care. This study had been conducted to find out the current prevalence and to assess various risk factors for PONV in the Indian population. MethodsAll patients above 18 years undergoing non-cardiac surgery under anaesthesia were selected from the daily operation theatre list by a systematic random sampling method. Koivuranta score was used to predict PONV in first 24 h post-operatively. ResultsPrevalence of PONV in the study population was found to be 25.6%. There was association detected between female gender, non-smokers and occurrence of PONV (CI 95%, p ≤ 0.001, 0.005, respectively). PONV was seen to be more common in patients with history of PONV in prior surgeries, in patients who underwent surgery under general anaesthesia and in patients where opioids were used in the post-operative period (95% CI, p ≤ 0.001, 0.001 and 0.001 respectively). General, laparoscopic, abdominal, orthopaedic, obstetric, breast and urological surgeries showed a significant association with occurrence of PONV (95% CI, p ≤ 0.05). ConclusionInspite of use of antiemetics (single or dual) being given as part of the institutional protocol, the incidence of PONV was still high. There is a need to update our knowledge regarding newer antiemetics and their inclusion in PONV management guidelines. There is need for further research to study various other possible risk factors which may contribute to occurrence of PONV.

RT-PCR Mediated Identification of SARS-CoV-2 Patients from Particular Regions of Bangladesh and the Multi-factorial Analysis Considering Their Pre and Post Infection Health Conditions

Background: SARS-CoV-2 is a type of coronavirus shows bizarre features with fatality rates at 34.4%. The clinical and non-clinical features of COVID-19 might be causative factors for more rapid community spreading compared to MERS and SARS-CoV-1.&#x0D; Objectives: To study the efficacy of RT-PCR based detection of SARS-CoV-2 patients. Besides, the patients' pre and post-infection health conditions depending on selective clinical and nonclinical parameters were analyzed.&#x0D; Materials and Methods: Clinical and non- clinical data were collected from 205 randomly selected COVID-19 patients, identified through RT-PCR from different areas of Bangladesh. The data were analyzed using statistical and analytical tools to illustrate the impact of the pandemic situation on the sufferers. &#x0D; Results: Molecular identification of the patients through RT-PCR has been observed as the most efficient option for detecting SARS-CoV-2 patients. Patients with the smoking habit have been reported to be more prone to the COVID-19 infection; surprisingly the non-smoker female was the worse suffers. The patients aged 60-69 years were the worst sufferers with every adverse health conditions mentioned. Professionally, 28% self-employed male and 8.19% female were infected. The most infected individuals were house wife (32.029%), as next to the health care workers (22.1%). With the increased age group, a decreased number of smokers were found. Nebulization of 5% home and 12% hospital treated patients were provided, with Oxygen for 26% of hospitalized patients. After recovery, combined physical and psychological complications were observed in 19% of male and 11% female. The socioeconomic, environmental and geographical annotations exposed a clear relationship with the rate of infection as revealed from the nonclinical data analysis.&#x0D; Conclusion: RT-PCR proved its specialty in COVID-19 detection. In addition, impacts of different clinical and nonclinical factors on the physical conditions of the nCoV patients were found significant in the research.

Sub-clinical levels of attention deficit-hyperactivity disorder are associated with tobacco consumption in male but not in female smokers

An abudance of evidence has demonstrated an association between symptoms of attention deficit hyperactivity disorder (ADHD) and tobacco consumption. However, previous research has focused solely on populations meeting full diagnostic criteria for ADHD, despite evidence suggesting that symptoms below diagnostic threshold can be associated with impairment. Furthermore, the role of gender in the relationship between ADHD symptoms and tobacco consumption has not been determined. To examine the relationship between ADHD symptoms, tobacco use, and gender in a non-clinical population, symptoms of inattention, hyperactivity and impulsivity were assessed in 230 undergraduate students (22 male and 45 female smokers, and 66 male and 97 female nonsmokers). Overall, relative to nonsmokers, the smoking subjects reported significantly higher levels of inattention and hyperactivity. In male smokers, both inattentive and hyperactive/impulsive symptoms were positively associated with the number of cigarettes smoked daily. This relationship did not hold for female smokers, for whom no association was found between symptoms and nicotine consumption. Findings imply that even sub-clinical levels of inattention and hyperactivity/impulsivity are related to indices of tobacco use in males, and support previous research suggesting that significant gender differences may exist in tobacco smoking motives. Results also have potential implications for tobacco cessation programs, which may require more individual tailoring.l glutamic pyruvic transaminase is identified in an elderly subject.

Induction of remission in female rheumatoid arthritis patients is associated with stabilization of myocardial abnormalities: a prospective cardiac magnetic resonance follow-up study

Objectives: To study whether female patients with active rheumatoid arthritis (RA) have myocardial abnormalities and whether progression of myocardial involvement can be attenuated by disease-modifying anti-rheumatic drugs (DMARDs). Method: Cardiac magnetic resonance (cMR; 1.5 or 3.0 T), including late gadolinium enhancement (LGE), T1 relaxation time, and ventricular functions, was performed in 30 patients with untreated active early RA starting first DMARDs, and 28 patients with chronic RA with inadequate response to conventional synthetic DMARDs starting biological DMARDs. cMR was repeated in RA patients 1 year later. cMR was conducted once in 22 fibromyalgia (FM) subjects and in 35 healthy volunteers serving as controls. All subjects were non-smoking females without coronary heart disease, heart failure, or diabetes. Results: Compared with controls, 58 RA patients had slightly lower ventricular function, although in the normal range, and longer T1 time at baseline. None of the FM subjects had LGE, but it was frequent in RA (67%). During the 1 year DMARD treatment, Disease Activity Score based on 28-joint count–C-reactive protein declined, ventricular functions tended to improve, but the number of patients with LGE remained unchanged. However, the number of LGE-positive heart segments either decreased or stayed the same in 91% of RA patients. In early RA patients, achieving tight remission was associated with LGE stabilization, after adjustment for age, metabolic syndrome, baseline inflammatory activity, and leisure-time physical activity. Conclusion: Treatment targeted to tight remission in early stages of RA seems to be important to prevent not only joint damage but also myocardial abnormalities.

Associations between smoking habits and major adverse cardiovascular events in patients who underwent coronary computed tomography angiography as screening for coronary artery disease.

We analyzed whether smoking was associated with major adverse cardiovascular events (MACE) and the progression of coronary atherosclerosis as assessed by coronary computed tomography angiography (CCTA) as screening for coronary artery disease (CAD). We enrolled 443 patients who had all undergone CCTA and either were clinically suspected of having CAD or had at least one cardiovascular risk factor. We divided the patients into smoking (past and current smoker) and non-smoking groups and into males and females, and evaluated the presence of CAD, severity of coronary atherosclerosis and MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization) with a follow-up of up to 5years. %CAD and the severity of coronary atherosclerosis in the smoking group were significantly higher than those in the non-smoking group. %MACE in males and smokers were significantly higher than those in females and non-smokers, respectively. Interestingly, Kaplan-Meier curves also showed that female non-smokers enjoyed significantly greater freedom from MACE than female smokers (p = 0.007), whereas there was no significant difference in freedom from MACE between male non-smokers and male smokers (p = 0.984). Although there were no significant predictors of MACE in all patients according to a multiple logistic regression analysis, smoking was useful for predicting MACE in females, but not males. In conclusion, smoking was significantly associated with MACE in females, but not males, who underwent CCTA as screening for CAD.

Exploratory research on developing lung cancer risk prediction model in female non-smokers

Objective: To develop a lung cancer risk prediction model for female non-smokers. Methods: Based on the Kailuan prospective dynamic cohort (2006.05-2015.12), a nested case-control study was conducted. Participants diagnosed with primary pathologically confirmed lung cancer during follow-up were identified as the case group, and others were identified as the control group. A total of 24 701 subjects were included in the study, including 86 lung cancer cases and 24 615 control population, respectively. Questionnaires, physical examinations, and laboratory tests were conducted to collect relevant information. Multivariable-adjusted logistic regressions were conducted to develop a lung cancer risk prediction model. Area Under the Curve (AUC) and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration, respectively. Ten-fold cross-validation was used for internal validation. Results: Two sets of models were developed: the simple model (including age and monthly income) and the metabolic index model [including age, monthly income, fasting blood glucose (FBG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C)].The AUC (95%CI) [0.745 (0.719-0.771)] of the metabolic index model was higher than that of the simple prediction model [0.688 (0.660-0.716)] (P=0.004). Both the simple model (PHL=0.287) and the metabolic index model (PHL=0.134) were well-calibrated. The results of ten-fold cross-validation indicated sufficient stability, with an average AUC of 0.699 and a standard error (SD) of 0.010. Conclusion: By incorporating metabolic markers, accurate and reliable lung cancer risk prediction model for female non smokers could be developed.

Exposure to bisphenol A and epigenetic modification in aged population

Background: Bisphenol A (BPA) is an environmental endocrine disrupting chemical affecting public health. So our research aim was to determine whether BPA exposure affects epigenetic mechanisms or not.Methods: We recruited 45 non-smoker females, who were aged 60 years. Participants visited our center 3 times with 1 week interval. On every visit, their urine and blood samples were collected for BPA and epigenome-wide miRNA level measurements, respectively. We evaluated relationships between urinary BPA and miRNA levels. Results: Five miRNAs (miR-1224-3p, miR-138-5p, miR-184, miR-543, and miR-587) were positively associated with BPA exposure (p&lt;0.05 for all 5 miRNAs). The predicted target genes of 5 miRNAs were found to be related with various disease classes including metabolic, cardiovascular, and chemdependency. Furthermore, KEGG pathways on pathway in cancer (hsa05200), PI3K-Akt signaling pathway (hsa04151), and MAPK signaling pathway (hsa04010) in order of precedence were related with BPA exposure. Conclusions: Our study results suggest a potential that BPA exposure modifies epigenetic mechanisms, resulting in a variety of diseases.

Salvage anlotinib showed sustained efficacy in heavily pretreated EGFR wild-type lung adenocarcinoma

Rationale:Anlotinib has been proved to be effective in advanced refractory non-small cell lung cancer.Patient concerns:A 47-year-old female non-smoker was admitted due to persistent chest tightness for a month.Diagnoses:Epidermal growth factor receptor (EGFR) wild-type advanced primary lung adenocarcinoma without brain or bone metastasis.Interventions:The patient failed 2 lines of pemetrexed/docetaxel plus carboplatin and third-line erlotinib. Fourth-line anlotinib was administered thereafter.Outcomes:The pulmonary lesions showed partial remission 5 months after anlotinib monotherapy. The patient demonstrated a progression-free survival of more than 7 months and an overall survival of >12 months. The adverse events including hypertension and fatigue were well-tolerated.Lessons:Salvage anlotinib might be a reasonable choice in EGFR wild-type lung adenocarcinoma after failure of chemotherapy. Further well-designed trials are warranted to verify this occasional finding.

Smoking cessation increases levels of osteocalcin and uncarboxylated osteocalcin in human sera

Smoking is thought to be a risk factor for osteoporosis development; however, the consequences of stopping smoking for bone homeostasis remain unknown. Here we conducted two separate human studies and show that bone mineral density was significantly lower in smokers than in non-smokers. The first was an observational study of pre- and post-menopausal healthy female smokers and non-smokers; the second included 139 current smokers determined to stop smoking. In the second study, levels of bone formation markers such as osteocalcin and uncarboxylated osteocalcin significantly increased after successful smoking cessation, as verified by significantly reduced levels of serum cotinine, a nicotine metabolite. Moreover, nicotine administration to mice reduced bone mineral density and significantly increased the number of osteoclasts in bone. Reduced bone mass phenotypes seen in nicotine-treated mice were significantly increased following nicotine withdrawal, an outcome accompanied by significantly reduced serum levels of tartrate-resistant acid phosphatase, a bone resorption marker. Taken together, our findings suggest that bone homeostasis is perturbed but can be rescued by smoking cessation.

A RARE TWIST: LYMPHANGIOLEIOMYOMATOSIS PLUS DIFFUSE LARGE B-CELL LYMPHOMA

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a rare systemic disease resulting in cystic lung destruction, recurrent pneumothoraces, chylous pleural effusions, and abdominal tumors. This multisystem disease most commonly affects women of childbearing age, resulting in stepwise decline in pulmonary function, with clinically apparent hypoxemia developing in most patients within a decade after onset of symptoms. Here we present a rare case of late-onset LAM with concurrent high grade B-cell lymphoma. CASE PRESENTATION: The patient is a 62-year-old female nonsmoker with a remote history of spontaneous pneumothorax who presented due to pleuritic chest pain at rest. Chest CT revealed innumerable pulmonary cysts up to 15 mm, few solid noncalcified pulmonary nodules, multiple complex mediastinal lesions, and a 30% left anterior pneumothorax. Chest tube was placed; the patient was admitted. A nontender swelling was noted on the skull which the patient attributed to a work injury several months prior. MRI showed a 5 cm lytic lesion involving the left frontal bone and subgaleal space with hypercellular diffusion pattern. Craniectomy with resection was performed; pathology revealed high-grade B cell lymphoma. CT abdomen revealed a 4x4 cm right-sided irregular exophytic renal mass. The patient had VEGF-D level of 1382 pg/mL, which, combined with diffuse cystic lung disease, was consistent with a diagnosis of LAM. The patient was discharged and underwent chemotherapy and radiation in the outpatient setting. Two months later, she was readmitted with recurrent left pneumothorax. She failed doxycycline chemical pleurodesis (as there was a nation-wide talc shortage) and went for VATS decortication, pleurectomy, LLL wedge resection, and mechanical pleurodesis. Immunohistochemistry studies on lung pathology confirmed LAM (Table 1). DISCUSSION: LAM may develop sporadically, or may arise in a patient with preexisting tuberous sclerosis complex. The clinical presentation varies and may include cough, dyspnea, recurrent pneumothorax, pleural effusion, or respiratory failure. Overall, the patient’s family history and clinical presentation was not consistent with tuberous sclerosis complex. This is a case of likely sporadic LAM in a patient with recurrent pneumothorax, the first being 5 years prior to this presentation. The concurrent diffuse large B cell lymphoma of the skull adds an interesting twist, as there have only been case reports of LAM occurring with malignant lymphoma. CONCLUSIONS: Although LAM is diagnosed at a median age of 35, more women are being diagnosed at an older age. Pleurodesis after the first occurrence of pneumothorax should be considered due to the high rate of recurrence, as seen in this patient who had multiple pneumothoraces and failed chemical pleurodesis. Sirolimus is also recommended for LAM but this patient’s concurrent treatment for lymphoma complicates her treatment options. Reference #1: McCormack FX, Gupta N, Finlay GR, et al. Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. Am J Respir Crit Care Med. 2016;194(6):748-761. doi:10.1164/rccm.201607-1384ST Reference #2: Park S, Lee EJ. Diagnosis and treatment of cystic lung disease. Korean J Intern Med. 2017 Mar;32(2):229-238. doi: 10.3904/kjim.2016.242. Epub 2017 Feb 28. Reference #3: Jawad H, Walker CM, Wu CC, Chung JH. Cystic interstitial lung diseases: recognizing the common and uncommon entities. Curr Probl Diagn Radiol. 2014 May-Jun;43(3):115-27. doi: 10.1067/j.cpradiol.2014.01.001. DISCLOSURES: No relevant relationships by Helen Li Mitchell, source=Web Response No relevant relationships by Sushant Soni, source=Web Response No relevant relationships by Justin Thomas, source=Web Response No relevant relationships by Shawnt Tosonian, source=Web Response

A RARE PRESENTATION OF GRANULOMATOSIS WITH POLYANGITIS

SESSION TITLE: Fellows Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a small to medium vessel vasculitis, usually ANCA positive. Clinically this disease is difficult to diagnose, as presentations vary. Patients can have ear, nose, and sinus disease as well as rapidly progressive glomerulonephritis.1 Renal complications occur in up to 75% of patients.1 Rare pulmonary complications include alveolar hemorrhage, nodules, and cavitary lesions. Seldom these patients have mediastinal lymphadenopathy and obstructive lung disease.2 Here we present a case of a woman who developed pulmonary nodules, lymphadenopathy, and obstructive lung disease due to GPA. CASE PRESENTATION: Our patient is a 75yo female nonsmoker with a history of polymyalgia rheumatica in remission that endorsed one year of dyspnea on exertion, hoarseness, and 20 lb weight loss. PFTs noted obstructive ventilatory defect meeting criteria for severe COPD. CT chest revealed multiple pulmonary nodules, mediastinal lymphadenopathy, and emphysematous change throughout of unknown duration as she did not have any previous imaging. CT-guided biopsy pathology showed chronic inflammatory changes, but no malignant cells. PET scan had hypermetabolic nodules bilaterally worrisome for metastasis. Bronchoscopy noted subglottic edema, but we were unable to pass ETT, so EBUS and ENB were aborted. She was noted to have mucosal inflammation throughout the tracheobronchial tree. Repeat CT-chest showed bilateral spiculated nodules increasing in size and number compared to prior scan. Second CT-guided biopsy pathology showed chronic inflammation and fibrosis with small noncaseating granulomas. Based on in-house and outside pathology consult, it was decided she likely had GPA. After evaluation by rheumatology she started rituximab infusions, but pulmonary nodules remained stable in size. P and c-ANCA were negative, along with negative c-ANCA by immunofluorescence. RF, CCP, ESR, CRP and renal function were within normal limits. CT maxillofacial was negative. DISCUSSION: When a vasculitis is suspected, a negative ANCA does not exclude the diagnosis of GPA, so further investigations, such as biopsy, should be considered. The lung is the most common site biopsied. Our case presented a diagnostic challenge given her presentation with a COPD-like syndrome and significant weight loss, as well as p-ANCA negativity. By some estimates <10% of cases of GPA present with isolated disease, such as in our patient.3 CONCLUSIONS: Prompt diagnosis for GPA is needed as the mortality is high without treatment. Treatment includes immunosuppression with glucocorticoids, methotrexate, azathioprine or cyclophosphamide.1 Our case highlights the importance of the pathologist in the diagnosis of small vessel vasculitis to lead the care team to the correct and rapid diagnosis. Reference #1: Seo P, Stone JH. The Antineutrophil Cytoplasmic Antibody-Associated Vasculitides. Am J Med. 2004; 117: 39-50. Reference #2: George TM, Cash JM, Farver C, et al. Mediastinal mass and hilar adenopathy: rare thoracic manifestations of Wegener's granulomatosis. Arthritis Rheum. 1997;40:1992–1997. Reference #3: Ananthakrishan L, Sharma N, Kanne JP. Wegner's Granulomatosis in the Chest: High-Resolution CT Findings. AJR 2009: 192; 676-682. DISCLOSURES: My spouse/partner as a Consultant relationship with Abbvie Please note: $1-$1000 Added 05/27/2020 by Ebtesam Islam, source=Web Response, value=Consulting fee No relevant relationships by Ximena Solis, source=Web Response

Exposure to organophosphorus insecticides and increased risks of health and cancer in US women

Results of this paper provide evidence that chronic long-term exposure to organophosphorus insecticides poses a significantly higher health risk for US women than for men, based on dialkylphosphate biomarker data from NHANES cycles 2003-2012. The risk of cardiovascular disease for female non-smokers aged 60-85 years in the highest dimethylthiophosphate (DMTP) urinary concentration quartile is 3.0 (odds ratio, OD = 3.0, 95%CI 1.4-6.4) times higher than that in the lowest quartile. Women with higher urinary DMTP concentrations also have significantly higher risk of asthma at the ages 6-39 years and an apparently higher risk of chronic bronchitis at the ages 60-85. Overall cancer risk is significantly higher for female non-smokers aged 60-85 years in the higher urinary DMTP quartiles (OD = 2.7, 95% CI 1.3-5.9). Increasing risks of breast cancer for female smokers and prostate cancer for male smokers aged 60-85 years with higher exposure to organophosphorus insecticides in the US are also significant.

Environmental tobacco smoke and cancer risk, a prospective cohort study in a Chinese population

Few prospective cohort studies have investigated associations between environmental tobacco smoke (ETS) and other cancer sites, in addition to lung cancer. We assessed these associations in a population-based prospective cohort study started from 2008 to 2011 with average of 9.1 years of follow-up, in Minhang district, Shanghai, China. The study included a total of 23,415 participants (8388 men, 15,027 women) and 205,515 person-years. Epidemiological data were collected by a standardized questionnaire including ETS exposure. Newly diagnosed patients with primary cancers and deaths were identified by record linkage system with the Shanghai Cancer Registry and Shanghai Vital Statistics. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models, adjusting for potential confounders. During the study period, a total of 1462 patients with diagnoses of primary cancers were identified. Among all participants and non-smokers, ETS was associated with an increased risk of all smoking-related cancers (all: adjusted HR: 1.23, 95% CI: 1.05–1.43 and non-smokers: 1.24, 1.02–1.49), lung cancer (1.29, 0.98–1.71 and 1.27, 0.91–1.77), and stomach cancer (1.86, 1.21–2.85 and 1.75, 1.05–2.91), respectively. Furthermore, associations for lung and stomach cancers were the strongest among non-smoking females. The joint effects of both ETS and active smoking were strongest for all cancers, all smoking-related cancers, lung cancer, and stomach cancer. No clear interactions were observed. These results suggest that ETS exposure may increase the risk of smoking-related cancers in a Chinese population. Further studies on the relationship between ETS exposure and specific cancer sites are warranted to replicate our findings.

Sex-related associations of high-density lipoprotein cholesterol with aortic stiffness and endothelial glycocalyx integrity in treated hypertensive patients.

Smoking, a well-recognized major cardiovascular (CV) risk factor, impairs endothelial function and increases aortic stiffness which indicates subclinical organ damage in hypertensive patients. Loss of endothelial glycocalyx (EG) integrity, as part of the endothelium, represents endothelial dysfunction. The authors aimed to investigate the role of increased HDL cholesterol levels (HDL-C), which usually are considered protective against CV disease, in aortic stiffness and endothelial integrity in middle-aged treated hypertensive patients regarding smoking habit. The authors studied 193 treated hypertensive patients ≥40years (mean age=61±11years, 58% females), divided in four groups regarding sex and smoking. Increased perfusion boundary region of the 5-9μm diameter sublingual arterial microvessels (PBR5-9 ) was measured as a noninvasive accurate index of reduced EG thickness. Aortic stiffness was estimated by carotid-femoral pulse wave velocity (PWV). In the whole population, an inverse weak relationship was found between HDL-C and PWV (r=-.15, P=.03) and PBR5-9 (ρ=-.15, P=.03). Moreover, HDL-C was negatively related to PBR5-9 in males (r=-.29, P=.008) either smokers (r=-.35, P<.05) or non-smokers (r=-.27, P<.05) and PWV in female non-smokers (r=-.28, P=.009). In a multiple linear regression analysis, using age, weight, smoking, HDL-C, and LDL-C as independent variables, we found that HDL-C independently predicts PWV in the whole population (β=-.14, P=.02) and PBR5-9 in male hypertensive patients (β=-.28, P=.01). Higher HDL-C levels are associated with reduced aortic stiffness in hypertensive patients, while they protect EG and subsequently endothelial function in middle-aged, treated hypertensive male patients (either smokers or not).

Impact of the COVID-19 lockdown on diabetes patients in Jeddah, Saudi Arabia

AimsTo explore the impact of the coronavirus disease lockdown on diabetes patients living in Jeddah, Saudi Arabia, in terms of their compliance with medication intake and lifestyle habits, and quality of life. MethodsIn this cross-sectional, qualitative prospective study, a questionnaire was administered over the telephone to diabetes patients who had attended National Guard primary care centers in Jeddah, Saudi Arabia. The survey included questions on demographic data, type of diabetes, medications used, comorbidities, medication compliance, and daily habits before and after the lockdown, and those assessing patients’ psychological parameters during the past month by using the Kessler Psychological Distress Scale (K10). Data analysis was performed using SPSS program version 26. ResultsTotally, 394 patients participated. All of them had type 2 diabetes, and 37.6% had only one comorbidity. Antidiabetic monotherapy was used in 76.4% of the patients, while combination therapy was used in 23.6%. The compliance score before the lockdown was significantly higher (18.49 ± 3.05) than that after it (17.40 ± 3.25) (p-value <0.001). The average psychological assessment score was 9.78 ± 4.14 (range 8–35). Male participants and smokers had a significantly better psychological status than female participants (p-value = 0.002) and non-smokers (p value < 0.001), respectively. ConclusionsThe patients’ levels of compliance with medications and healthy lifestyle habits were significantly reduced after the lockdown. These findings highlight the need for healthcare professionals to encourage diabetes patients to adhere to healthy lifestyle habits and use telemedicine during lockdowns to ensure optimal blood glucose control and reduce the incidence of complications.

Effect of passive smoking on heavy metals concentration in blood and follicular fluid of patients on going ICSI

Purpose: To assess the effects passive smoking and heavy metal concentrations in the blood and follicular fluid on assisted reproductive technology outcome.Methods: A prospective study was conducted between March 2017 and January 2018 in population consisted of 75 female patients undergoing an In vitro fertilization (IVF) cycle at Dr. Faris Medical center for Infertility and Human Reproduction located on Heliopolis, Cairo, Egypt; with unexplained infertility who underwent intracytoplasmic sperm injection (ICSI) using GnRH-antagonist protocol. Concentrations of three toxic metals Cadmium (Cd), Lead (Pb) and Arsenic (As) were measured both in blood sera and follicular fluid specimens. Patients were evaluated in two groups both undergoing ICSI; the first group consisted of patients who does not smoke or exposed to smoking (n=28) and the group passive smoker females (n=47). Results: These three heavy metals were significantly higher in serum and follicular fluid of passive smoking females (P<0.05). Also, higher concentrations of Cd, Pb and As were found in follicular fluid of passive smoking patients in comparison with non-smoker females. However, concentrations of Cd and Pb were not significantly different between both serum and follicular fluid. Conclusion: Passive smoking could affect levels of Cd, Pb and As in serum and follicular fluid of females undergoing Intra Cytoplasmic Sperm Injection (ICSI). Keywords: Cadmium (Cd); Lead (Pb); Arsenic (As); Follicular fluid (FF); Intra Cytoplasmic Sperm Injection (ICSI); heavy metals