Tobacco Abuse Research Articles

Theorizing the Role of Dopaminergic Polymorphic Risk Alleles with Intermittent Explosive Disorder (IED), Violent/Aggressive Behavior and Addiction: Justification of Genetic Addiction Risk Severity (GARS) Testing.

Scientific studies have provided evidence that there is a relationship between violent and aggressive behaviors and addictions. Genes involved with the reward system, specifically the brain reward cascade (BRC), appear to be associated with various addictions and impulsive, aggressive, and violent behaviors. In our previous research, we examined the Taq A1 allele (variant D2 dopamine receptor gene) and the DAT-40 base repeat (a variant of the dopamine transporter gene) in 11 Caucasian boys at the Brown School in San Marcus, Texas, diagnosed with intermittent explosive disorder. Thirty supernormal controls were screened to exclude several reward-deficit behaviors, including pathological violence, and genotyped for the DRD2 gene. Additionally, 91 controls were screened to exclude ADHD, pathological violence, alcoholism, drug dependence, and tobacco abuse, and their results were compared with DAT1 genotype results. In the schoolboys vs. supercontrols, there was a significant association with the D2 variant and a trend with the dopamine transporter variant. Results support our hypothesis and the involvement of at least two gene risk alleles with adolescent violent/aggressive behaviors. This study and the research presented in this paper suggest that violent/aggressive behaviors are associated with a greater risk of addiction, mediated via various genes linked to the BRC. This review provides a contributory analysis of how gene polymorphisms, especially those related to the brain reward circuitry, are associated with violent behaviors.

Clinical Profile of Posterior Circulation Stroke: A Prospective Study at Dhaka Medical College Hospital

Studies regarding clinical characteristics of stroke involving the posterior circulation territory of the brain in Bangladesh are rare although large number of patients were found in hospital admission and with a high morbidity and mortality. Study for better understanding of the clinical features, risk factors and aetiologies of posterior circulation stroke (PCS) may be very helpful for early diagnosis, treatment, and also for setting primary and secondary prevention strategies. The objective of the study was to identify clinical features and short-term outcome of PCS. Adult patients admitted in Dhaka Medical College Hospital with clinical features consistent with posterior circulation stroke involving brain stem or, cerebellum or thalamus or occipital area and confirmed by computer tomography (CT) scan of brain were the the cases as respondents. Few cases were needed MRI of brain to confirm diagnosis. This was a hospital based prospective observational study with descriptive and analytical component. Sample was selected from the study population by purposive type of non-probability sampling technique. Sample size was 30. A semi-structured questionnaire was prepared containing patients’ profile as well as stroke patients’ reporting form which included all the essential information regarding clinical profile of PCS as well as short term outcome. Analysis was done using Statistical Package for the Social Sciences (SPSS) software. Thirty consecutive cases of strokes involving posterior circulation territory were included in the study according to inclusion and exclusion criteria. Male female ratio was 1.7:1. Most of the patients in both sexes were affected after the age of 50 years. Hemorrhagic PCS was significantly higher than ischaemic PCS. Among hemorrhagic PCS common symptoms were decreased level of consciousness and motor disturbances. Most common clinical sign in ischemic PCS is impaired consciousness which was present in 55.6% of the total ischemic PCS cases. Whereas this sign was present in all the cases of hemorrhagic PCS (100%). Like presenting symptoms, most of the clinical signs were also more common in hemorrhagic PCS. But few clinical signs were more common in ischemic strokes, such as cranial nerve involvement and nystagmus. Commonest predisposing factors were tobacco abuse, hypertension and dyslipidemia. Mortality was higher in hemorrhagic PCS than ischemic PCS within 7 days of follow up.
 Bangladesh Med J. 2021 Sept; 50(3): 20-25

The tumor microenvironment-relay station for prognosis and therapy response

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with adismal prognosis. Besides tobacco and alcohol abuse, human papilloma virus (HPV) infection is an independent risk factor, particularly in oropharyngeal squamous cell carcinomas (OPSCC). One key determinant of therapy response and prognosis is the tumor immune microenvironment (TIME). Astrong anti-tumor immune response represents an important mechanism of tumor cell killing. Another major determinant is the tumor metabolism. One feature of tumor cells is their reliance on glycolysis instead of oxidative phosphorylation (OXPHOS) for energy production despite sufficient oxygen supply.The presented studies were based on several different clinically and pathologically well annotated HNSCC cohorts. Immunohistochemical stainings were performed on tissue microarrays and whole slides against p16, different immune cell markers, and metabolic markers. DNA and mRNA were extracted to detect HPV and assess immune-related and metabolic genes via RT-PCR and Nanostring.An initial assessment of HPV infection frequencies in different HNSCC cohorts showed that socioeconomic and regional factors strongly influence HPV prevalence. An analysis of the immunological and metabolic differences of HPV-positive and HPV-negative OPSCC demonstrated an enhanced anti-tumor immune response together with increased levels of OXPHOS metabolism in HPV-positive OPSCC. In asubsequent study, astrong anti-tumor immune response together with an OXPHOS metabolism was associated with improved short-term survival in HNSCC. Finally, TIME differences of HNSCC primary tumors and recurrent tumors were analyzed to understand the poor therapeutic response of recurrences and discovered an overall decrease of tumor infiltrating lymphocytes with significant loss of CD8-positive Tcells and Blymphocytes as well as asignificant decrease of tertiary lymphoid structures in recurrences after chemoradiation.These results demonstrate the clinical and molecular differences of HPV-positive and HPV-negative HNSCC with afocus on OPSCC. Furthermore, they delineate the interdependencies of TIME and tumor metabolism in HNSCC in general and stress their impact on therapy response. Additionally, they show an impairment of anti-tumor immune response in recurrences after chemoradiation, which indicates immune evasion as one recurrence driver.

Treatment-Free Remission in Chronic Phase Chronic Myeloid Leukemia Patients Treated with Nilotinib Front-Line, in Real-Life Conditions: Influence of Switching to Another TKI Prior to Cessation.

Nilotinib (NIL) as front-line therapy in newly diagnosed chronic phase (CP) CML patients (pts) is able to induce high rates of sustained deep molecular response and high possibilities of treatment-free remission (TFR). However, the identification of factors influencing successful TFR in this population remains imprecise. This observational study retrospectively analyzed TFR rates, outcome, and tried to identify factors related to successful TFR in in- and out-study 221 pts treated in this setting with NIL 600 mg, in "real-life" conditions. All pts with newly diagnosed adult CP-CML receiving NIL 300 mg BID alone front-line between 10/2007 and 06/2022, were eligible. Data were retrospectively collected according to the national regulations with pts' information. All pts were assessed and followed according to ELN recommendations 2006→2020 along treatment and to the recommendations of the Fi-LMC (D. Rea et al., Cancer 2018, i. e. 2 years of sustained MR4.5) in case of TFR. In this regard, a TKI was resumed if loss of MMR on one instance. BCR::ABL1 assessments were performed in the 2 reference laboratories, standardised, and expressed in % (IS) with ≥32,000 copies of ABL1 as control. The primary endpoints were the rate of successful TFR on NIL first-line. Secondary endpoints were the kinetics of molecular response, factors influencing outcome, survival, and safety of NIL. Two hundred and one patients were enrolled with 56% males with a median age at diagnosis of 50 (17.5-83) years, and 26% of them had cardiovascular risk factors at onset (tobacco abuse 10%, hypercholesterolemia 9.55%, diabetes 1.36%, none with history of cardiovascular events [CVE]). ELTS scores were high in 13%, intermediate in 30% and low in 53% of pts, unknown in 4% of pts. Twenty-six (12%) pts harboured additional chromosomal abnormalities (ACA) at diagnosis. The median follow-up after NIL initiation was 85.16 (5.72-174) months. After a median of 37.7 months, 119 pts (58%) were not on NIL anymore for toxicities, resistance or TFR. Sixty-eight (31%) pts obtained the TFR criteria and stopped NIL after a median of 66.7 (27-132) months. The median time between first MR4.5 datapoint and TFR was 39 (15.31-120) months. With a median follow-up of 20.3 (0.03-108) months after NIL cessation, the survival without MMR loss after NIL cessation (figure 1.) is 64.38% (95% CI: 53.35- 77.69). Interestingly, no CVE occurred after NIL cessation, as well as no blast crisis. Two patients died in TFR from competitive events (2 solid tumours). We went on comparing the TFR group vs the non-TFR group. The median age at TFR was 56 (30-87) years with no difference at CML diagnosis in terms of age (49 vs 50 years, p=0.096), ELTS (p=0.276), ACA (15% vs 11%, p=0.483) between the 2 groups. In contrast, there was a difference in favour of female vs male gender in the TFR group (56%) vs non-TFR group (39%, p=0.031), and the median time to reach MMR was shorter in the TFR group 5.04 vs 10.2 months, p<0.001; as well as the median time to reach MR4.5 in the TFR group 18.2 vs 36.1 months, p<0.001. We finally compared the successful vs the unsuccessful TFR pts requiring TKI-rechallenge, in univariate analysis and multivariate analyses. The univariate analysis identified pts that have switched to another TKI before TFR for whatever reasons was a risk factor for subsequent loss of MMR [HR: 3.09 (95% CI: 1.30-7.34), Cox p-value=0.011]. This was confirmed by the log-rank survival curves of TFR in patients with or without switch (figure 2., log-rank p=0.008). Surprisingly, neither the duration of NIL before TFR [HR: 0.98 (0.96-1.00), Cox p-value=0.072], nor the duration of MR4.5 prior to NIL cessation [HR: 0.98 (0.95-1.01), Cox p-value=0.15] were found to have an impact. Additionally, the prognostic scores did not influence TFR success on NIL. The multivariate analysis confirmed that switching to another TKI was an unfavourable risk factor for molecular relapse [HR: 2.87 (1.20-6.84), p-value=0.018], and that the lack of impact of the duration of MR4.5 [HR: 0.98 (0.95-1.01), Cox p-value=0.218] had no significant influence. NIL first-line is able to induce high rates of successful TFR in newly diagnosed CP CML patients and switching to another TKI for toxicity and/or resistance, prior to TFR, represents an unfavourable risk factor for the success of TKI cessation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pancreatic Enzyme Replacement Therapy in Patients with Non-pancreatic Digestive Conditions: A Nationwide Claims Analysis.

Pancreatic enzyme replacement therapy (PERT) is most commonly used to treat exocrine insufficiency related to pancreatic diseases, but can be used for non-pancreatic digestive conditions (NPDC). We aimed to determine the prevalence of PERT use and describe prescription patterns in individuals with NPDC. A nationally representative claims database of 48.6 million enrollees was used to identify individuals who received PERT prescription(s) in the absence of any pancreas-related diagnosis. Data on demographics, enrolment, comorbidities, exocrine function testing, treatment and potential indications for PERT were retrieved, and compared with individuals who received PERT for primary diagnosis of chronic pancreatitis (CP). A total of 29,234 individuals (64.1% female, mean age 52.4 ± 16.5years) received PERT for NPDC. The overall estimated US population prevalence rate for PERT use for NDPC was 60.2/100,000 persons. Rates increased significantly with age and were higher in women in all age groups except 1-20years old. When compared with CP, individuals with NPDC receiving PERT were more likely to be older (52.4 vs. 50.1years), female (64.1% vs. 51.0%), have lower prevalence of alcoholism (3.6% vs. 25.0%), tobacco abuse (8.4% vs. 30.1%), and received PERT for shorter mean duration (5.3 vs. 8.2months) (all p < 0.001). Median dose of PERT in individuals with NPDC was 2880 lipase units/day. Although proportionally low, a sizable population receives PERT for NPDC. PERT for NPDC is usually prescribed at a low dose and for shorter duration, suggesting it is used mostly as a trial for or until resolution of symptoms.

Abstract 14522: Infective Mitral Valve Endocarditis in an Immunocompetent Patient Caused by Lactobacillus Species Transmitted by Intranasal Cocaine Use

A 59-year-old male with controlled DM2, HTN, tobacco abuse, and remote MSSA bacteremia secondary to longstanding intranasal cocaine use (never IV drug user) presented to the ER with acute onset of left leg pain. He was in extreme distress and examination showed a cold left leg with absent extremity pulses. Cardiac assessment was notable for an apical systolic murmur. Magnetic resonance angiography (MRA) of the leg revealed a thrombotic occlusion of the left common femoral artery extending into the popliteal artery prompting emergent successful femoral artery thrombectomy and compartment fasciotomy. An intraoperative TEE revealed mobile echodensities on the anterior and posterior MV leaflets with severe eccentric mitral regurgitation (MR) [Figure1]. Blood and thrombectomy debris cultures yielded Lactobacillus acidophilus vs. gasseri species. Further workup showed multiple small embolic infarcts on MRA head and chronic sinusitis on CT sinuses, while CT chest, abdomen and pelvis were unremarkable. He received IV ampicillin for 1 week with bacterial clearance, followed by bioprosthetic mitral valve replacement. Gram stain of the mitral valve revealed gram positive rods, cultures grew Lactobacillus species, and histopathology confirmed the presence of infective endocarditis. The patient completed 7 weeks of penicillin G intravenously with clinical recovery. Lactobacillus acidophilus and gasseri are normal flora of the human oral cavity, gastrointestinal and genitourinary tracts. Lactobacillus endocarditis is rare and has been identified in only 0.05-0.4% of endocarditis cases. Infections primarily affect the immunocompromised, but to the best of our knowledge this is the first case of Lactobacillus mitral valve endocarditis presenting with concomitant acute limb ischemia with infected thromboembolic debris in an immunocompetent individual with the suspected inciting event being intranasal cocaine use causing trauma to the nasal vasculature.

Cervical neoplasia in relation to socioeconomic and demographic factors - a nationwide cohort study (2002-2018).

Cervical cancer is a major cause of mortality and morbidity. We aimed to estimate the association between sociodemographic factors and cervical neoplasia. In this Swedish nationwide open cohort study, 4 120 557 women aged ≥15 years at baseline were included between January 1, 2002 and December 31, 2018. The two outcomes were cervical cancer and carcinoma in situ identified in the Swedish Cancer Register. Sociodemographic factors (age, education level, family income level, region of residency, country of origin) were the main predictors. Incidence rates per 10 000 person-years were calculated. Cox regression was used to estimate hazard ratios. Sensitivity analyses were conducted, including parity, urogenital infections, alcohol- and drug-use disorders, and chronic obstructive pulmonary disease (used as a proxy for tobacco abuse). In 38.9million person-years of follow-up, 5781 (incidence rate: 1.5, 95% confidence interval [CI] 1.4-1.5) and 62 249 (incidence rate 16.9, 95% CI 15.9-16.1) women were diagnosed with cervical cancer and carcinoma in situ, respectively. Women from Eastern Europe had a hazard ratio of 1.18 (95% CI 1.05-1.33) for cervical cancer compared with Swedish-born women, while women from non-Western regions were inversely associated with cervical cancer and carcinoma in situ. Women with a low education level had a hazard ratio of 1.37 (95% CI 1.29-1.45) for cervical cancer compared with women with a high education level. Women from the Middle East and Africa living in Sweden seem to suffer less from cervical neoplasia, whereas women with low education and women from Eastern Europe seem to suffer more from cervical cancer.

Percutaneous Deep Venous Arterialization: Treatment of Patients with End-Stage Plantar Disease.

Percutaneous deep venous arterialization (pDVA) is a minimally invasive technique connecting the tibial arteries below the knee to the tibial venous system into plantar venous circulation to deliver oxygenated blood to otherwise nonperfused foot. This study demonstrated outcomes of pDVA with commercially available equipment and described single-center experience on pDVA for critical limb-threatening ischemia patients with small artery diseases and end-stage plantar disease (ESPD) who were deemed no-option cases. A single-center retrospective review was performed on patients who underwent pDVA. Primary end points were successful establishment of tibial vein flow with venous pedal loop, rate of major amputation, and major adverse events over 6 months. Secondary end points were primary and secondary patency rates, minor amputation rates, and wound healing over 6 months. Forty-two patients with ESPD underwent pDVA. Risk factors identified were hypertension (92.8%), hyperlipidemia (85.7%), diabetes (78.6%), tobacco abuse (42.9%), and chronic kidney disease ≥ stage 3 (42.8%). Three patients were categorized as Rutherford Class 4, 14 patients Class 5, and 25 patients (59.5%) Class 6. Of 42 procedures, 33 (78.6%) were deemed successful. Amputation-free survival at 6 months was reported in 25 patients (60.9%); 16 patients (38.1%) reported minor amputations. Wound healing rate reported at 6 months was 23.8%. This is one of the largest case series to date with real-world no-option patients undergoing pDVA. pDVA seems a reasonable option for limb salvage in patients with ESPD where traditional arterial revascularization is not feasible. Identifying criteria for patient selection and advanced wound care is important to ensure clinical success. Additional research is required to establish diagnostic guidelines for patients being evaluated for pDVA.

PSAT024 A Case of Mild Autonomous Cortisol Secretion Managed with Active Surveillance

Abstract Mild autonomous cortisol secretion is characterized by the failure to suppress cortisol sufficiently after dexamethasone administration but without the stigmata of overt Cushing's syndrome. This condition, diagnosed in up to 50% of adrenal incidentalomas, has low overall rates of progression and mild cases can present a treatment dilemma. Here we describe one such case of cortisol excess well managed with a surveillance strategy rather than surgical intervention. A 49-year-old female with a past medical history of hypothyroidism was evaluated in the endocrine clinic for an incidental adrenal mass. CT imaging revealed a 2.7 cm left adrenal nodule, stable in size compared to prior imaging, with features typical of benign adrenocortical adenoma. Initial 1 mg DST with 8 am cortisol of 11.7µg/dl. Late night salivary cortisol (LNSC)level was found to be elevated at 130 ng/dl (nl&amp;lt;100 ng/dL). At that time, 24-hour urine free cortisol (UFC) was found to be borderline at 23.98 µg/day (nl&amp;lt;24 µg/day). Further testing at 6 months and 1 year from initial assessment showed persistently elevated LNSC level (110 ng/dL) and stable 24-hour UFC at 24 µg/day. Morning ACTH level was 19 pg/mL. One year after initial assessment, LNSC continued to be elevated at 0.106 µg/dL (nl &amp;lt;0.010–0.090 µg/dL) and repeat overnight 1 mg DST with 8am cortisol was unsuppressed at 10 mcg/dL representing at least two years of autonomous, mildly elevated cortisol levels. DHEA-S was low at 13.6 µg/dl (41.2 - 243.7 µg/dL). She had no history of diabetes, hypertension, obesity, hyperlipidemia or clinical osteoporosis. Her social history was negative for tobacco or alcohol abuse. Repeated physical exams were within normal limits, and she did not have any signs of central adiposity, abdominal striae, thinning of skin or hirsutism. She continued to deny any subjective symptoms of lethargy or muscle weakness. Given low normal range ACTH values, mildly increased midnight salivary cortisol, failure to suppress after 1 mg overnight DST with no clinical evidence of overt hypercortisolism, patient was diagnosed with mild autonomous cortisol secretion. She did not show any signs of hypertension, hyperglycemia or physical changes that would warrant concern for hypercortisolemic end organ effects. As the patient was largely asymptomatic, with stable CT imaging of left adrenal adenoma, left adrenalectomy was discussed but not recommended as patient preferred an observation surveillance strategy with laboratory evaluation every 6 months to monitor for hypercortisolemia. This case demonstrates that a surveillance strategy, rather than surgery, may be appropriate in selected cases of mild autonomous cortisol secretion from an incidentally discovered adrenocortical adenoma, especially when end organ effects of cortisol excess are clinically absent. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP245 Syndrome of Diabetic Ketoalkalosis due to Severe Hypercortisolemia: A Case Series

Abstract Introduction Decompensated diabetes (DM) precoma/comas states are major causes of hospital morbidity and mortality. These commonly include diabetic ketoacidosis (DKA), diabetic hyperglycemic hyperosmolar syndrome (DHHS), diabetic hypoglycemia coma (DHC) and diabetic lactic acidosis (DLA). Another less common decompensated DM precoma/coma state to be aware of is Diabetic ketoalkalosis (DKAL). We present two cases of DKAL due to severe hypercortisolemia (HCS) from ectopic Cushing's syndrome (ECS). Clinical cases; Case 1 was a 61 yr old AA woman with suboptimally managed type 2 DM who had been admitted for DKA 2 months before. She had marked hyperglycemia (blood glucose &amp;gt;500mg/dl) on repeated measures (RMs) and chronic diarrhea with tachypnea and altered mental status (AMS). She had heavy tobacco abuse and work up revealed a right lung mass biopsy of which showed a malignant neuroendocrine tumor presumed to be malignant bronchial carcinoid. Her initial lab tests showed marked metabolic alkalosis with severe hypokalemia and elevated anion gap, ketonemia and ketonuria. Presentation was typical of DKAL and subsequent work up showed ECS with serum cortisol &amp;gt; 110 (n; 4.3-22.4ug/dl) on RMs and serum ACTH 377-480 (n; 0/46pg/ml). Her metabolic derangements were corrected and HCS managed with mild impact using ketaconazole and octreotide but she died within a month of admission with intractable septic shock despite parenteral antimicrobials. Case 2 was a 46 yr old Hispanic man with heavy tobacco abuse admitted on account of AMS, tachypnea and upper abdominal pain. He had severe hyperglycemia (blood glucose &amp;gt;750mg/dl on RMs) though not known to have DM. HBA1c was &amp;gt; 15% indicating undiagnosed DM. Initial lab tests showed marked respiratory and metabolic alkalosis, marked hyponatremia, hypokalemia, hypo-osmolality but with ketonemia and ketonuria. Presentation was consistent with DKAL. Work up showed a left lung lesion with pleural effusion shown to be small cell carcinoma of the lung. He was also found to have profound HCS (serum cortisol &amp;gt;150ug/d; on RMs) confirmed due to ECS with serum ACTH, 1500-1800pg/ml. Metabolic derangements were corrected and he was started on ketoconazole and etomidate to correct HCS with little response. Elective bilateral adrenalectomy was planned but patient abruptly discharged himself AMA. He was readmitted ∼ 3 weeks later with a massive pulmonary embolism and acute respiratory failure from which he never recovered. He died ∼ 2 months later. Discussion + Conclusions DKAL is an uncommon but important potential acute presentation of decompensated DM. Early recognition and management requires close attention to the acid-base and electrolyte derangements that often accompany it. Among the many possible causes of DKAL severe HCS is an important possibility to be consider. Rapid diagnosis and institution of aggressive therapy of HCS is crucial as it often has high morbidity and mortality potential. Presentation: No date and time listed

Trends in Substance Use and Abuse During COVID-19 Among the General Population.

COVID-19 pandemic has brought many public health issues, including substance use and abuse. Individuals abusing substances are vulnerable to severe infections caused by SARS-CoV-2 virus as well as impairment of the immune system, mental health, and physical health. Despite considerable efforts to minimize and prevent substance use, the use of tobacco, alcohol, and illicit substances is ever increasing resulting in morbidity and mortality which significantly leads to socio-economic costs. A quantitative review of the literature searched in PubMed and Google Scholar databases yielded a total of 1416 studies among which 27 cross-sectional studies, conducted on the general population of 15 and above years of age, were selected based on the eligibility criteria. A sample of 1,021,118 individuals were investigated in this study. The most commonly used substances were marijuana (100%), methadone (69.86%), and large cigar (60%). A total of 26 substances were reported to have been used during pandemic, 13 of which showed trends in usage (increased/decreased/no change). Of the total sample, 45.89% were males, 54.14% females, and 1.28% others. Everyone and anyone is susceptible to alcohol, tobacco, and other substance use and abuse at different stages of their lives. Therefore, the need for effective preventive strategies is critical in community efforts to combat substance abuse. Combined efforts from local and global stakeholders will lead to curbing the issue of substance use and abuse worldwide.

Association of polymorphic variants of &lt;i&gt;GRIN2A&lt;/i&gt; and &lt;i&gt;GRIN2B&lt;/i&gt; genes with alcohol and tobacco abuse in patients with schizophrenia

Aim. To compare the frequency of genotypes for polymorphic variants of GRIN2A and GRIN2B genes in patients with schizophrenia and addictive behavior (alcohol / tobacco abuse) and in patients with schizophrenia without addictive behavior in the Slavic population of the Tomsk region.Materials and methods. The study included 219 inpatients with the established diagnosis of schizophrenia who received treatment in the clinics of Mental Health Research Institute and Tomsk Clinical Psychiatric Hospital. A history of alcohol / tobacco abuse was identified during a clinical interview and objective data collection. DNA was isolated from peripheral blood leukocytes by standard phenol – chloroform extraction.15 single nucleotide polymorphisms (SNPs) in the GRIN2A gene and 9 polymorphisms in the GRIN2B gene were selected for genotyping. Allelic variants were determined by real-time polymerase chain reaction (PCR) with specific primers. The SPSS 17.0 software package was used for statistical data processing. The distribution of genotype frequency was assessed using the Pearson’s χ2 test with the Yates’ correction and the Fisher’s exact test.Results. Significant differences in the allele frequency for the rs9788936 polymorphism in the GRIN2A gene (χ2 = 4.23, p = 0.04) and for the rs10845838 polymorphism in the GRIN2B gene (χ2 = 4.27, p = 0.04) were reveled between the groups of patients with and without alcohol abuse. It was found that the polymorphic variant rs8049651 of the GRIN2A gene had a clear association (F = 8.06, p = 0.029) with the development of tobacco addiction in patients with schizophrenia.Conclusion. The study identified the association between alcohol abuse and the rs9788936 polymorphism in the GRIN2A gene and the rs10845838 polymorphism in the GRIN2B gene in patients with schizophrenia. The association between the rs8049651 and rs7190619 polymorphisms in the GRIN2A gene and the development of tobacco abuse in patients with schizophrenia was revealed.

BLAST VS MASS: USE OF FLEXIBLE BRONCHOSCOPY AND ENDOBRONCHIAL ULTRASOUND IN THE MEDICAL ICU

BLAST VS MASS: USE OF FLEXIBLE BRONCHOSCOPY AND ENDOBRONCHIAL ULTRASOUND IN THE MEDICAL ICU

A CASE OF LUNG TRANSPLANT WITH RECENTLY INFECTED SARS-COV-2 DONOR LUNGS

A CASE OF LUNG TRANSPLANT WITH RECENTLY INFECTED SARS-COV-2 DONOR LUNGS

Development of multiple intracranial aneurysms: beyond the common risk factors.

The prevalence of multiple intracranial aneurysms (MIAs) has increased over the last decades. Because MIAs have been identified as an independent risk factor for formation, growth, and rupture of intracranial aneurysms (IAs), a more profound understanding of the underlying pathophysiology of MIAs is needed. Therefore, the authors' extensive institutional aneurysm database was analyzed to elucidate differences between patients with a single IA (SIA) and those with MIAs. A total of 2446 patients seen with or for IAs at the University Hospital of Essen, Essen, Germany, from January 2003 to June 2016 were included in this retrospective cohort study and were separated into MIA and SIA subgroups. Patient data were screened for sociodemographic and radiographic parameters, preexisting medical conditions, and results of blood examinations. These parameters were analyzed for their correlations with MIAs and absolute number of IAs. MIAs were identified in 853 (34.9%) patients. In multivariable analysis, MIAs were independently associated with female sex (p = 0.001), arterial hypertension (p = 0.023), tobacco abuse (p = 0.009), AB blood group (p = 0.010), and increased admission values for C-reactive protein (p = 0.006), mean corpuscular volume (p = 0.009), and total serum protein (p = 0.034), but not with diagnostic modality (3D vs 2D digital subtraction angiography, p = 0.912). Absolute number of IAs was independently associated with female sex (p < 0.001), arterial hypertension (p = 0.014), familial predisposition to IA (p = 0.015), tobacco consumption (p = 0.025), increased mean corpuscular volume (p = 0.002), and high platelet count (p = 0.007). In this sizable consecutive series of patients with IAs, the authors confirmed the impact of common IA risk factors on the genesis of MIAs. In addition, specific hemorheological and hemocytological features may also contribute to the development of MIAs.

S222 Patients With Eosinophilic Colitis Have Comparable Rates of Colorectal Cancer Compared to Patients With Ulcerative Colitis

Introduction: Eosinophilic colitis (EoC) is a rare entity characterized by the presence of high eosinophilic infiltrate into the colonic wall in symptomatic patients, in the absence of known other causes of colonic eosinophilia. Recently proposed guidelines suggest 100 eosinophils per high-power-field in the ascending colon, 85 in the descending, and 65 in the sigmoid colon as diagnostic thresholds. Whereas ulcerative colitis (UC), is known to be associated with an increased risk of colorectal cancer (CRC), little is known of the association between EoC and CRC. We aimed to compare EoC patients to UC patients to assess their odds of developing CRC. Methods: Using the multi-institutional, health research network database TriNetX (Cambridge, MA), de-identified, aggregated clinical data were obtained on patients with a diagnosis of either EoC or UC. Patients with other identifiable causes of eosinophilia were excluded from the EoC cohort, including inflammatory bowel disease, food allergies, helminth infections, and other eosinophilic gastrointestinal disorders. A 1:1 propensity score matching method was used to stratify EoC and UC patients. Matched variables were age at diagnosis, sex, race, obesity, tobacco abuse, alcohol abuse, and family history of digestive tract malignancy. Odds ratios(OR) and confidence intervals (CI) were calculated for development of CRC and subsequent colonoscopies for each cohort. Results: A total of 1,310 and 195,477 EoC and UC patients were identified, respectively (Table). The higher proportion of EoC patients were female compared to UC patients (65.4% vs 54.4%), and were African American (11.9% vs 9.2%). More EoC patients reported tobacco usage (4.6% vs 2.5%) and were obese (11.8% vs 7.0%) compared to UC patients. A 1:1 matching ratio stratified 1,310 patients into each cohort. After adjusting for the aforementioned covariates, EoC patients had an OR of 1.304 (95% CI 0.828-2.054, p-value 0.2503) of developing CRC compared to UC patients (Figure). EoC patients demonstrated an OR of 0.754 (95% CI 0.583-0.976, p-value 0.0313) of undergoing subsequent surveillance colonoscopies after initial diagnosis of disease compared to UC patients. Conclusion: Patients with a diagnosis of EoC have a similar risk of developing colorectal cancer compared to UC patients. Despite this, EoC patients are less likely to undergo subsequent surveillance colonoscopy compared to UC patients. Hopefully, our data can be used for future prospective studies investigating the natural course of EoC.Figure 1.: Forest plot showing odds ratios and confidence intervals of development of colorectal cancer (CRC) and subsequent surveillance colonoscopies in EoC patients compared to UC patients Table 1. - Baseline patient characteristics of EoC (eosinophilic colitis) and UC (ulcerative colitis) patients before and after 1:1 propensity score matching Baseline Patient Characteristics Before Matching p-value After Matching p-value EoC(n=1,310) UC(n=195,477) EoC(n=1,310) UC=n1,310) Age at Diagnosis 54 +/- 17.2 51 +/- 17.6 < 0.0001 54 +/- 17.2 54 +/- 17.4 0.9451 Sex Female 857(65.4%) 106,402(54.4%) < 0.0001 857(65.4%) 865(66.1%) 0.7419 Male 453(34.6%) 89,075(45.6%) < 0.0001 453(34.6%) 445(33.9%) 0.7418 Race African American 157(11.9%) 17,934(9.2%) 0.0005 157(11.9%) 134(10.2%) 0.1527 Asian 32(2.4%) 3,583(1.8%) 0.1014 32(2.4%) 39(2.9%) 0.3997 Caucasian 980(74.8%) 145,147(74.3%) 0.6468 980(74.8%) 1,007(76.9%) 0.2178 Other/Unknown 141(10.9%) 28,813(14.7%) < 0.0001 141(10.9%) 130(10.0%) 0.6152 Other Covariates Alcohol abuse 18(1.4%) 3,241(1.7%) < 0.0001 18(1.4%) 151(11.5%) 0.8078 Family history of GI cancer 38(2.9%) 4,033(2.1%) < 0.0001 38(2.9%) 49(3.7%) 0.2818 Obesity 155(11.8%) 13,688(7.0%) 0.4222 155(11.8%) 12(0.9%) 0.2706 Tobacco use 60(4.6%) 4,807(2.5%). 0.0338 60(4.6%) 31(2.4%) 0.3931

S3516 A Case of Recurrent Thromboangiitis Obliterans (Buerger's Disease) in a Patient With Abdominal Pain and Intestinal Transplant

Introduction: We describe a case of abdominal pain and recurrent disease following intestinal transplant in a patient with a history of mesenteric ischemia and Thromboangiitis obliterans (Buerger's syndrome) that did not resolve with standard medical therapy. Case Description/Methods: A wonderful 44 year old female presents with intestinal infarction. The patient required three prior revascularization procedures with acute on chronic mesenteric ischemia with superior mesenteric artery thrombosis. She was taken to the operating room for necrotic small bowel with resection 20 centimeters distal to the ligament of treitz and placed on parenteral nutrition. Following recurrent episodes of line related bacteremia and fungemia she was listed for intestinal transplantation. After being off tobacco for a year she received and small bowel and right colon transplant. She had initial anticoagulation which was restarted four year later after a deep venous thrombosis to the lower extremity. Seven years following transplant the patient had inconsistent use of the anticoagulation along with recurrent tobacco abuse and developed recurrent mesenteric ischemia with acute on chronic occlusion of the celiac trunk, superior mesenteric artery, and inferior abdominal aorta leading to generalized abdominal pain, ischemic colitis and septic shock. Given recurrent abdominal infections patient had enterectomy 8 years and six months following intestinal transplantation. The patient subsequently developed bacteremia, candidemia and line related thrombosis. Patient had eventual transition to palliative management and died. Discussion: Buerger's disease (also known as thromboangiitis obliterans) affects blood vessels in the body, most commonly in the arms and legs. The use of tobacco is essential for both the initiation and progression of this disease. Blood vessels swell, which can prevent blood flow, causing clots to form. This can lead to pain, tissue damage, and even gangrene. It is typically treated with medications that dilate blood vessels, improve blood flow or dissolve blood clots, such as anticoagulants. Ongoing tobacco cessation is vital to success following rare intestinal transplantation. We present a case of intestinal transplant for Buerger’s Disease with recurrent thrombosis seven years following intestinal transplant attributed to recurrent tobacco abuse.

UNDERSTANDING THE NEED FOR A BROAD DIFFERENTIAL DIAGNOSIS: A CASE OF PNEUMONIC TULAREMIA

UNDERSTANDING THE NEED FOR A BROAD DIFFERENTIAL DIAGNOSIS: A CASE OF PNEUMONIC TULAREMIA

A SENSE OF IMPENDING DOOM: MASSIVE AORTIC ABDOMINAL ANEURYSM PRESENTING AS SUBACUTE BACK PAIN

A SENSE OF IMPENDING DOOM: MASSIVE AORTIC ABDOMINAL ANEURYSM PRESENTING AS SUBACUTE BACK PAIN

S2417 A Diagnosis That Is Difficult to Swallow: Digging Deeper for Answers

Introduction: Esophageal parakeratosis (EP) is an uncommon finding with largely unknown clinical implications and malignant potential. Here, we report a case of severe esophageal parakeratosis. Case Description/Methods: Patient is a 69-year-old African American male with history significant alcohol and cocaine abuse, prior tobacco abuse, keloids, gastroesophageal reflux, food impaction, and progressive dysphagia for 20 years with 40-pound weight loss. Patient’s first esophagogastroduodenoscopy (EGD) in 2000 revealed moderate esophagitis and a distal esophageal stricture with 9 mm lumen bougie dilated to 12 mm, but dysphagia persisted. Repeat EGDs between 2006 and 2016 showed whitish plaques with no evidence of fungal organisms. Given classic appearance of EOE, he was trialed on empiric fluticasone and budesonide with no improvement in dysphagia. In September 2021, he was hospitalized with severe dysphagia. EGD (Figure) at this time showed gray, yellow frondlike lesion replacing esophageal lumen from mid to distal esophagus with mucosal friability. His dysphagia transiently responded to repeat dilations, but continued to recur and worsen. Unfortunately, patient continued to have weight loss and dysphagia unresponsive to dilations. The patient was then started on gastric tube feedings. He was offered surgery due to the severity of his symptoms, but he declined. Most recently, the patient underwent endoscopic mucosal resection with deeper tissue samples revealing superficial fragments of laterally spreading squamous cell carcinoma of the esophagus. Discussion: In this case, there was a high clinical suspicion for malignancy, leading the endoscopist to obtain deeper tissue samples via endoscopic mucosal resection as superficial fragments of the esophagus only revealed parakeratosis. It is important to trust clinical judgment, especially if there is a high suspicion for malignancy. Tylosis also has a known association with EP and often presents with areas of thickened skin plaques on palms and feet. Tylosis has a strong association with head, neck, and esophageal squamous cell carcinoma. The patient had no family history of tylosis and no cutaneous features. Despite this, a careful inspection of the entire EP area with targeted biopsies should be obtained to evaluate for dysplasia. This case represents EP with years of no evidence of squamous cell cancer despite aggressively searching for it, which at least anecdotally suggests a precancerous potential for EP.Figure 1.: A. Initial EGD B. Recent EGD.