Smoking Dose Research Articles

Transcriptome Analysis of Rat Lungs Exposed to Moxa Smoke after Acute Toxicity Testing.

The increasing use of moxibustion has led to a debate concerning the safety of this treatment in human patients. Inhalation of cigarette smoke induces lung inflammation and granulomas, the proliferation of alveolar epithelial cells, and other toxic effects; therefore, it is important to assess the influence of inhaled moxa smoke on the lungs. In the present study, a novel poisoning cabinet was designed and used to assess the acute toxicity of moxa smoke in rats. We evaluated pathological changes in rat lung tissue and analyzed differentially expressed genes (DEGs) using RNA-seq and transcriptomic analyses. Our results show that the maximum tolerable dose of moxa smoke was 290.036 g/m³ and LC50 was 537.65 g/m³. Compared with that of the control group, the degree of inflammatory cell infiltration in the lung tissues of group A rats (all dead group) was increased, while that in group E rats (all live group) remained unchanged. GO and KEGG enrichment analyses showed that the DEGs implicated in cell components, binding, and cancer were significantly enriched in the experimental groups compared with the profile of the control group. The expressions of MAFF, HSPA1B, HSPA1A, AOC1, and MX2 determined using quantitative real-time PCR were similar to those determined using RNA-seq, confirming the reliability of RNA-seq data. Overall, our results provide a basis for future evaluations of moxibustion safety and the development of moxibustion-based technology.

Comorbidity Evaluation Identifies Smoking Dose Density to be Associated with TP53 Mutation in Myeloid Malignancies

Background: Inflammation and aging are factors associated with mutagenicity. In acute Myelogenous Leukemia (AML), detectable mutations (mut) are a powerful tool for identification of patients (pt) at a higher risk for relapse. One frequently observed mutation is TP53, which is particularly unresponsive to treatment. Known risk factors for TP53 acquisition include prior chemotherapy or radiation exposure. It is possible that TP53 mut initiates at low allele frequency and expands in a “permissible marrow microenvironment”. Cell extrinsic inflammation, collectively called extracellular stressor, is a theory of mutation acquisition which is gaining momentum given its recently recognized role in clonal initiation, expansion, and dominance. Smoking is one such possible extracellular stressor that dramatically increases risk of human cancer. Lung tissue directly exposed to smoking develops higher frequency of mut; however, other tissue not directly exposed (e.g. bladder, pancreas) exhibit similar mutation frequencies. This suggests that active smoking metabolites systemically induce inflammation and/or mutagenicity. Indeed, TP53 and ASXL1 mut have been associated with clonal hematopoiesis (CH). In this study, we seek to create “proof of clinical concept” for association between smoking “dose” and TP53 myeloid malignancy development when controlled by an age-adjusted effect. Methods: After IRB approval, AML and Myelodysplastic Syndrome (MDS) AML patients with available Next Generation Sequencing (NGS) were isolated from MDS/AML databases. “Smoking dose” was estimated in patients exhibiting or not exhibiting TP53 mut by standard pack-year calculation. Demographics, clinical, and laboratory categorical and continuous variables were analyzed by chi-square and t-test using SAS software. Logistic regression analysis allowed for identification of variables with independent predictive value for TP53 acquisition. Results: Our cohort represented 52 patients (pt) [AML N=47/52 (90.3%) and MDS N=5/52 (9.6%)]. 23/52 (44.2%) pt harbored TP53-mut and 29/52 pt (55.8%) were part of a genomic control group harboring ASXL1, RUNX1, FLT3, NPM1, and KRAS mut. Median age for pt with and without TP53 mut was 71 y (49-81) vs 60 y (22-88), respectively, p= 0.04 [Fig. 1B]. In TP53 mutated vs TP53 unmutated group, 14/23 (60.8%) vs 13/20 (65%) pt were male. 9/23 (39.1%) and 7/20 (35%) of pt with and without TP53 mut had available smoking history. Pack-year smoking was 53.6 [20-100] and 23.2 [10-40], in pt wit and without TP53 mut, respectively, p=0.02 [Fig. 1A]. When adjusted by age and prior chemotherapy exposure, smoking dose density was the only potential factor with relevance for TP53 acquisition (p=0.05). Conclusions: In myeloid malignancies, our data suggests that TP53 acquisition is associated with a dose dependent smoking history. This smoking dose dependency seems to be independent from aging and prior chemotherapy exposure in AML. Previous studies have demonstrated strong associations between smoking and inflammation. It is possible that higher dosages of smoking induce marrow microenvironment inflammatory changes permissible for TP53 initiation. These microenvironmental changes may be associated with mutational signatures similar to those found in other smoking-associated malignancies, including lung adenocarcinoma. Our report adds to the body of evidence for mechanistic link between magnitude of smoking exposure and marrow environmental stress to promote selective mutagenicity, though larger study is needed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of smoking on the eradication of Helicobacter pylori.

Although the association between the eradication of Helicobacter pylori (H. pylori) and smoking has been confirmed through a meta-analysis, many new studies have reported inconsistent conclusions. An up-to-date meta-analysis based on published relevant studies was conducted in this study to address this issue. Eligible studies up to January 2021 were screened and retrieved using PubMed and Web of Science as well as by performing a manual review of references. We calculated the pooled odd ratios (OR) with the 95% confidence interval (CI). Subgroup and sensitivity analyses were also performed. Begg's test was used to determine the publication bias. In total, 39studies were included in the meta-analysis. The results showed that smoking increases the failure rate of H. pylori eradication treatment (OR=1.70, 95%CI, 1.49-1.93). The risk of failure also increases with an increase in the smoking dose (>5 cigarettes per day) (OR=2.59, 95%CI, 1.28-5.24) and the current smoking status (continued to smoke during treatment) (OR=2.49, 95%CI, 1.52-4.06). Studies with a large proportion of patients with peptic ulcer (OR=2.14, 95%CI, 1.51-3.02) revealed a higher failure rate among smokers than those with a low proportion of patients with peptic ulcer (OR=1.57, 95%CI, 1.36-1.81). When vonoprazan (VPZ) was used to treat H. pylori infection, smoking did not affect the eradication rate (OR=0.94, 95%CI, 0.51-1.75). Smoking increases the failure rate of H. pylori eradication treatment. The risk of H. pylori eradication failure in smokers increases with a current smoking status and a high smoking dose. However, when VPZ is used to treat the H. pylori infection, smoking has no effect on the eradication rate.

Impact of genetic testing and smoking on the distribution of risk factors in patients with recurrent acute and chronic pancreatitis

Objective The aim of the present study is to assess the impact of smoking dose and duration on the distribution of risk factor(s) in patients with RAP and CP, and the impact of genetic testing on the distribution of risk factor(s) in patients with idiopathic RAP and CP. Methods All adult patients with RAP and CP referred to a multidisciplinary pancreatitis clinic between 2010 and 2017 were evaluated. Risk factors included alcohol and smoking, hypertriglyceridemia, biliary, and other etiologies. Genetic testing was only pursued in patients with idiopathic RAP or CP. Results Among the 1770 patients evaluated, 167 had RAP and 303 had CP. After genetic testing and smoking, the most common risk factors for RAP and CP were pathogenic variant(s) (23%) and the combination of alcohol and smoking (23%), respectively. Genetic testing and smoking assessment decreased the proportion of patients with alcoholic RAP from 17% to 5%, alcoholic CP from 33% to 10%, idiopathic RAP from 49% to 12%, and idiopathic CP from 54% to 14%. Pathogenic CFTR variants were the most common variant in patients with RAP (51%) and CP (43%). Among the 68 patients with pancreas divisum, other risk factor(s) were identified in 72%. Conclusion Genetic testing and a detailed assessment of smoking dose and duration reduce the proportion of patients with alcoholic and idiopathic pancreatitis. Other risk factor(s) for pancreatitis are found in the majority of patients with pancreas divisum further questioning its role as an independent risk factor. 1. What is the current knowledge? Approximately 30% of patients with pancreatitis have no clear risk factor(s) and are categorized as having an idiopathic etiology. Pathogenic variant(s) as well as smoking dose and duration are well-established risk factors for recurrent acute and chronic pancreatitis but are not widely recognized or incorporated into clinical practice. 2. What is new here? Genetic testing and a detailed assessment of smoking dose and duration reduced the proportion of patients with alcoholic and idiopathic acute recurrent and chronic pancreatitis. Approximately three-fourths of patients with pancreas divisum have a risk factor for pancreatitis.

Association of SLC22A1 rs622342 and ATM rs11212617 polymorphisms with metformin efficacy in patients with type 2 diabetes.

Metformin is the first-choice oral anti-hyperglycemic drug for type 2 diabetes mellitus (T2DM) patients. There are controversies about the association of SLC22A1 rs622342, which was not reported in the Chinese population, and ataxia-telangiectasia mutated (ATM) rs11212617 polymorphisms with metformin efficacy in T2DM. Our study was to investigate the effects of the two single nucleotide polymorphisms on the efficacy of metformin in T2DM of Han nationality in Chaoshan China. After enrollment, 82 newly diagnosed T2DM patients went on 2-month metformin monotherapy. According to BMI before treatment, the patients were divided into a normal weight group (≥18.5 and <25 kg/m2) and an overweight group (BMI ≥ 25 and <30 kg/m2). T-test, Pearson χ2 test, and regression analysis, which adjusted for age, BMI, sex, the dose of metformin, education, tea drink, smoking, and sweet, were used to evaluate the effects of rs622342 and rs11212617 on several variables, such as fasting plasma glucose (FPG). Compared with the AA or CC genotype, patients with AC genotype of rs622342 achieved greater reduction in Δ60FPG and Δ(60-30)FPG (P = 0.00820, 0.00089, respectively). For 11212617, the reduction in Δ30FPG and Δ60FPG was significantly different among patients with the AC genotype (P = 0.00026, 0.00820, respectively). Our results indicated that common variants of SLC22A1 rs622342 and ATM rs11212617 were associated with the efficacy of metformin in T2DM of Han nationality in Chaoshan China.

Acute Pain Burden and Opioid Dose Requirements after Cesarean Delivery in Parturients with Preexisting Chronic Back Pain and Migraine.

Introduction Preexisting chronic pain has been reported to be a consistent risk factor for severe acute postoperative pain. However, each specific chronic pain condition has unique pathophysiology, and it is possible that the effect of each condition on postoperative pain is different. Methods This is a retrospective cohort study of pregnant women with preexisting chronic pain conditions (i.e., migraine, chronic back pain, and the combination of migraine + chronic back pain), who underwent cesarean delivery. The effects of the three chronic pain conditions on time-weighted average (TWA) pain score (primary outcome) and opioid dose requirements in morphine milligram equivalents (MME) during postoperative 48 hours were compared. Results The TWA pain score was similar in preexisting migraine and chronic back pain. Chronic back pain was associated with significantly greater opioid dose requirements than migraine (12.92 MME, 95% CI: 0.41 to 25.43, P=0.041). Preoperative opioid use (P < 0.001) was associated with a greater TWA pain score. Preoperative opioid use (P < 0.001), smoking (P=0.004), and lower postoperative ibuprofen dose (P=0.002) were associated with greater opioid dose requirements. Conclusions Findings suggest women with chronic back pain and migraine do not report different postpartum pain intensities; however, women with preexisting chronic back pain required 13 MME greater opioid dose than those with migraine during 48 hours after cesarean delivery.

Chronic intake of valproic acid decreases total cholesterol level in adult population

Background: Valproic acid (VA) serve as the antimigraine, anti-mental disturbances agent and antiepileptic medicine. After using VA, metabolic rearrangements seen in patients that include alteration in lipoproteins levels; however, this topic is still under discussion and disputable. Aim: To discuss the effects of VA after using for long duration on total levels of cholesterol in adult. Methods: About Eighty candidates participated and they were divided into two groups namely, case group (40 candidates) and control groups40 candidates). All the candidates were asked for collection of venous blood sample in order to determine total cholesterol serum level among them via aid of enzymatic cholesterol oxidase phenol 4-aminoantipyrine peroxidase. By the aid of the logistic regression analysis, the relationship of the long-term VA treatment and the level of total cholesterol was obtained. With respect to our analysis, there is a co relation between total levels of cholesterol and long term usage of VA (P=0.003). Results: There were no noteworthy link for age, sex, body BMI, height medication usage, smoking, diabetes mellitus and VA dosage , except combination of anti-epileptic drugs Conclusion: In a net shell, by using VA for long duration, the total level of cholesterol in adults reduces. Keywords: Lipid profile, side effects, total cholesterol, valproic acid

Cigarette smoking may accelerate the progression of IgA nephropathy

BackgroundWhether cigarette smoking is associated with the progression of immunoglobulin A nephropathy (IgAN) remains uncertain; therefore, we aimed to evaluate the effect of cigarette smoking on the prognosis of IgAN.MethodsWe divided 1239 IgAN patients from West China Hospital of Sichuan University who met the inclusion criteria into smoker (current or former) and non-smoker groups. The endpoint was end-stage renal disease (ESRD: eGFR < 15 mL/min/1.73 m2 or undergoing renal replacement treatment) and/or eGFR decreased by > 50%. Kaplan–Meier, correlation, logistic regression and Cox proportional hazards analyses were performed. The association between cigarette smoking and IgAN was further verified by propensity-score-matched cohort analysis.ResultsDuring the mean follow-up period of 61 months, 19% (40/209) of the smoker group and 11% (110/1030) of the non-smoker group reached the study endpoint (p < 0.001). Multivariate Cox regression analysis revealed that cigarette smoking (hazard ratio (HR) = 1.58; p = 0.043) was an independent risk factor predicting poor renal progression in IgAN, and that IgAN patients with chronic kidney disease (CKD) stage 3–4 were more susceptible to cigarette smoking (p < 0.001). After propensity score matching (PSM), a significant correlation between cigarette smoking and renal outcomes in IgAN patients was seen. Furthermore, Spearman’s correlation test revealed that smoking dose was negatively correlated with eGFR (r = 0.141; p < 0.001) and positively related with proteinuria (r = 0.096; p = 0.001).ConclusionsCigarette smoking is an independent risk factor for IgAN progression, especially for advanced patients.

Cigarette Smoking, Complete Blood Count, and Myeloproliferative Neoplasms — a Meta-Analysis

IntroductionThe classic chronic Philadelphia-negative chronic myeloproliferative neoplasms (MPN) are acquired stem cell diseases and include essential thrombocythemia, polycythemia vera, primary myelofibrosis and unclassifiable MPN. Recently, these disorders have been described as “A Human Inflammation Model for Cancer Development”, reflecting chronic inflammation to be a major driving force for clonal evolution and disease progression in MPNs.The objectives of this meta-analysis were to investigate if cigarette smoking is associated with increased blood cell counts (CBC) and incidence of MPN as proof of concept.MethodA systematic review and meta-analysis was undertaken using databases Pubmed, EMBASE, Web of Science and World Health Organization Global Health Library for all relevant papers published until 15th February 2017 on smoking and complete blood counts and on smoking and myeloproliferative neoplasms according to a formal protocol that followed the PRISMA guidelines.Following data extraction, STATA 13.0 was used to calculate raw and standardized mean differences for CBC (in SI units) and pooled odds ratios for MPN with 95% confidence intervals using random and fixed effects models. Main analyses included analyses of current smokers, ex-smokers, and ever smokers vs. non- or never smokers. Heterogeneity was measured using I2 -statistical analysis and Cochrane Q statistic, and reported corresponding p-values and sensitivity analyses included among others gender and smoke dosage(heavy (>=20 cigarettes/day) and light(<20 cigarettes/day)). Funnel plots, Egger's test and Begg's tests were used to assess publication bias.ResultsComplete Blood Count (CBC): A total of 88 references published from 1974-2017 in 10 different languages and including 90 study populations with 533,242 individuals, 222,887 current smokers, 92,001 ex-smokers, and 222,538 non-smokers between the ages of 15 and 89 from 34 countries were analyzed.Meta-analyses showed that the mean of most CBCs were higher in smokers and ex-smokers compared to non-nonsmokers. Differences were larger comparing smokers to non-smokers than comparing ex-smokers to non-smokers, and also larger comparing heavy smokers to non-smokers than comparing light smokers to non-smokers. Furthermore, differences in most CBCs were higher in men compared to women.All analyses presented high heterogeneity in main and sensitivity analyses but no overall publication bias.Myeloproliferative Neoplasms (MPN): We included 5 studies with a total of 1,368,738 individuals and 2017 MPN cases. 2 studies were prospective and 3 studies case-control. Pooled odds ratio for MPN were 1.44 (95%CI: 1.33-1.56; p-value=5*10(-20); I-square=0%, p(heterogeneity)=0.56) comparing smokers to non-smokers, 1.10(0.86-1.41; p-value=0.46; I-square=71%, p(heterogeneity)=0.03) comparing ex-smokers to non-smokers, and 1.30(1.14-1.49; p-value=8*10(-5); I-square=45%, p(heterogeneity)=0.16) comparing ever-smokers to never smokers.ConclusionCurrent smokers, ex-smokers, and ever-smokers have higher mean CBCs and an increased risk of MPN compared to non-smokers. [Display omitted] DisclosuresHasselbalch:AOR Orphan: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Smoking Cessation and Coronary Artery Calcification in CKD.

Smoking is associated with vascular calcification and a higher risk of cardiovascular disease. In this study, we investigated the association of smoking dose and cessation with coronary artery calcification (CAC) in patients with CKD. From a nationwide, prospective cohort of Korean patients with CKD, 1914 participants were included. Prevalent CAC was defined as an Agatston score >0, using computed tomography. CAC progression was defined as ≥30%/yr increase in Agatston score at the 4-year follow-up examination in patients with baseline CAC. Prevalent CAC was observed in 952 (50%) patients. Compared with never smokers, former smokers had a similar prevalence ratio for CAC, but current smokers had a 1.25-fold higher prevalence ratio (95% confidence interval [95% CI], 1.10 to 1.42). Among former smokers, a lower smoking load of <10 pack-years (prevalence ratio, 0.77; 95% CI, 0.65 to 0.90) and longer duration of smoking cessation (prevalence ratio for 10 to <20 years, 0.85; 95% CI, 0.73 to 0.98: prevalence ratio for ≥20 years, 0.83; 95% CI, 0.73 to 0.96) were associated with lower risk of prevalent CAC compared with current smoking. The prevalence ratios did not differ between never smoking and long-term cessation. However, short-term cessation with heavy smoking load was associated with a higher risk of prevalent CAC (prevalence ratio, 1.21; 95% CI, 1.03 to 1.40) compared with never smoking. CAC progression was observed in 111 (33%) patients with baseline CAC. Compared with never smokers, former smokers showed a similar risk of CAC progression, but current smokers had a higher risk (relative risk, 1.92; 95% CI, 1.30 to 2.86). In CKD, former smoking with a lower smoking load and long-term cessation were associated with a lower risk of prevalent CAC than current smoking. CAC progression was more pronounced in current smokers.

Effect of Cigarette Smoking on Thyroid Cancer: Meta-Analysis.

BackgroundAlthough smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence.MethodsWe performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies.ResultsThe summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902).ConclusionOur results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.

Preconceptional smoking alters spermatozoal miRNAs of murine fathers and affects offspring\u2019s body weight

BackgroundActive smoking has been reported among 7% of teenagers worldwide, with ages ranging from 13 to 15 years. An epidemiological study suggested that preconceptional paternal smoking is associated with adolescent obesity in boys. We developed a murine adolescent smoking model before conception to investigate the paternal molecular causes of changes in offspring’s phenotype.MethodMale and female C57BL/6J mice were exposed to increasing doses of mainstream cigarette smoke (CS) from onset of puberty for 6 weeks and mated with room air (RA) controls.ResultsThirteen miRNAs were upregulated and 32 downregulated in the spermatozoa of CS-exposed fathers, while there were no significant differences in the count and morphological integrity of spermatozoa, as well as the proliferation of spermatogonia between CS- and RA-exposed fathers. Offspring from preconceptional CS-exposed mothers had lower body weights (p = 0.007). Moreover, data from offspring from CS-exposed fathers suggested a potential increase in body weight (p = 0.062).ConclusionWe showed that preconceptional paternal CS exposure regulates spermatozoal miRNAs, and possibly influences the body weight of F1 progeny in early life. The regulated miRNAs may modulate transmittable epigenetic changes to offspring, thus influence the development of respiratory- and metabolic-related diseases such as obesity, a mechanism that warrants further studies for elaborate explanations.

Reactions to reduced nicotine content cigarettes in a sample of young adult, low-frequency smokers.

Reducing nicotine content in cigarettes to ≤ 2.4mg per g of tobacco [mg/g] reduces smoking behavior and toxicant exposure among adult daily smokers. However, cigarettes with similar nicotine content could support continued experimentation and smoking progression among young adults who smoke infrequently. This study evaluated the threshold for nicotine in cigarettes that produces reactions associated with smoking progression in a sample of young adults who smoke infrequently. Young adults (n = 87, 18-25years, 49% female) using tobacco products ≤ 15days per month completed three counterbalanced, double-blinded sessions, each measuring positive and negative subjective reactions to fixed doses of smoke from investigational cigarettes containing one of three different nicotine contents: normal (NNC; 15.8mg/g); very low (VLNC; 0.4mg/g); and intermediate (INC; 2.4mg/g). In a final session, participants chose one of the cigarettes to self-administer. Post-cigarette breath carbon monoxide was greater for VLNC than for NNC (p < 0.001). Positive reactions were greater for NNC than INC (p < 0.001) and for INC than VLNC (p = 0.001). Negative reactions were greater for NNC than INC and VLNC (both p < 0.001); INC and VLNC did not differ. Cigarette choices did not differ from an even distribution (43% NNC, 25% INC, 32% VLNC), but choice for NNC or INC was associated with higher ratio of positive to negative reactions during the NNC and INC fixed dose sessions, respectively (p < 0.001). Reducing nicotine content will likely lower the abuse liability of cigarettes for most young, low-frequency smokers. Additional work is needed to determine if compensatory smoking may lead to increased toxicant exposure, and if a subset of individuals choosing lower nicotine cigarettes may continue to smoke regardless of nicotine content.

Is the Risk to Develop Osteoradionecrosis of the Jaws Following IMRT for Head and Neck Cancer Related to Co-Factors?

Background and Objectives: Determine the contribution of coexisting factors to the risk to develop Osteoradionecrosis (ORN) of the jaws among patients who have received radiotherapy by intensity modulated radiation therapy (IMRT) for head and neck cancer (HNC) between 2013 and 2016, in a single medical center. Materials and Methods: The records of all patients treated with IMRT for HNC between 2013 and 2016 in The Davidoff Center for the treatment and Research of Cancer in Rabin Medical Center—Beilinson hospital, Petah-Tikva, Israel were screened. Patients who have received a minimum mean dose of 40 Gy to the oral cavity entered the research and their medical records were retrospectively reviewed. Collected background data included: age, gender, smoking, diabetes mellitus (DM), ASA score, mean and maximal radiation doses (Gy), and diseases characteristics including histological diagnosis, primary tumor site, and disease stage. Results: A total of 1232 patients were surveyed. Out of all screened patients, 93 received a minimum mean dose of 40 Gy to the oral cavity. Out of the 93 patients, 7 (7.52%) developed ORN (ORN+) and 86 did not develop ORN (ORN−). Tumor type in all seven patients in the ORN+ group was Squamous Cell Carcinoma (SCC). In three out of those seven patients (42.9%), the tumor was located in the mandible. Conclusions: within the limits of the relatively small cohort in the current study, we suggest that the development of ORN due to Radiation therapy (RT) with IMRT is related significantly only to the location of a tumor in the mandible. Other co-factors do not significantly increase the risk to develop ORN when RT is delivered via IMRT.

The effect of cigarette smoke on the histopathological changes of the eustachian tube of Wistar rat

Background: Inflammation due to irritation of cigarette smoke causes metaplasia of the squamous epithelium of the Eustachian tube. Data on the prevalence and incidence of Eustachian tube dysfunction are still limited. The study aims to determine the effect of exposure to a stratified dose of cigarette smoke on the histopathological changes of the Eustachian tubes of Wistar rats.Method: This study was a true experimental study with post-test only control group design using Wistar rats as the subjects. We included 24 Wistar rats in the study and divided them into four groups. The number of Wistar rats in each group was 6. The control group was not exposed to cigarette smoke. The treatment group 1, 2, and 3 were each exposed to four cigarettes, eight cigarettes, twelve cigarettes per day for thirty days, respectively. We assessed the Eustachian tube histopathological changes using four parameters, namely inflammatory cells, cilia, goblet cells, and epithelium. Finally, we analyzed the data using the Kruskal-Wallis test and the Mann-Whitney test.Result: The Eustachian tube's histopathological changes occurred in inflammatory cells, cilia, goblet cells, and epithelial metaplasia. Group 1 showed grade 1 changes in all parameters assessed. Group 2 showed grade 2 changes in all parameters evaluated. Meanwhile, group 3 showed grade 3 changes in all parameters evaluated compared to other groups (p&lt;0.05). There was a significant difference between the treatment group and the control group (p&lt;0.05).Conclusion: Cigarette smoke with stratified doses affects the histopathological changes of the Eustachian tube.

A combined community health worker and text messagingbased intervention for smoking cessation in India: Project MUKTI - A mixed methods study.

INTRODUCTIONWe sought to evaluate the effectiveness of a community health worker (CHW) led smoking cessation intervention, supplemented by text messages, and tailored to an individual’s readiness to quit.METHODSWe conducted a cluster randomized controlled trial (April 2018–August 2019) in adult smokers residing in a semi-urban region of India. Participants in the intervention arm received CHW-led home visits and had the option of choosing to receive regular text messages. The dose and content of CHW counseling and text messages were tailored to the participant’s readiness to quit. The control group received brief education only. Primary outcome was biochemically verified smoking cessation at the end of 12 months. Both intention-to-treat and as-treated analyses were performed.RESULTSA total of 238 (mean age 43±12.3 years, male 96.2%) participants were enrolled; 151 (64%) in the intervention arm and 83 (35.4%) in the control arm. At 12 months, 31 (20.5%) participants in the intervention arm and 9 (10.8%) in the control arm quit smoking (absolute risk difference=9.7%; RR=1.69; 95% CI: 0.04–71.33, p=0.74). In the as-treated analysis, 17 (36.9%) of the 46 participants who received optimal dose of the intervention quit smoking.CONCLUSIONSCHW-led home-based counseling, supplemented by regular text messages, led to an increase in quit rates for smoking, especially among those exposed to a higher dose of the intervention. However, the difference in cessation rates was not statistically significant. Future studies should consider testing mobile application-based multimedia messaging with larger populations, as a supplement to CHW-based counseling.

Effects of cigarette smoke on oxidant–antioxidant system of lung tissue

The present study set out to investigate the effects of cigarette smoke on oxidant–antioxidant systems of homogenized bovine lung tissue and the possible protective effects of cigarette filters impregnated with vitamin C and lemon juice. Cigarette smoke was passed into bovine lung homogenate supernatant and malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, paraoxonase-1, nitric oxide synthase, and nitric oxide were determined. Malondialdehyde and nitric oxide levels were found to have increased as the dose of cigarette smoke increased and superoxide dismutase activity decreased with incremental doses of cigarette smoke exposure. Furthermore, the lemon juice impregnated filters scavenged nitric oxide. The cigarette smoke led to lipid peroxidation and a reduction in superoxide dismutase activity. Antioxidant-impregnated filters could not prevent oxidative stress.

Polygenic risk score in personalized screening of lung cancer: a prospective cohort study in Chinese

Objective: To explore how to personalize lung cancer screening programs for prevention in Chinese populations based on individual genetic risk score. Methods: We constructed the lung cancer polygenic genetic risk score (PRS-19) based on the 19 previously published genetic variations, using 100 615 participants with genotyping data from the China Kadoorie Biobank (CKB). Using the 5-year absolute risk of lung cancer in a population (55 years old with at least 30-pack-year history of smoking) as reference, the trend of 5-year absolute risk in different genetic risk groups was calculated in smokers and non-smokers, respectively. Distribution curves of 5-year absolute risk were also described to determine the theoretical age or smoking dose when different genetic risk groups reached the reference values. Given the overall findings, the specific start age for lung cancer screening were suggested for different genetic risk groups. Results: The 5-year absolute risk of lung cancer was 0.67% in 55-year-old smokers with 30 packs per year in the CKB. Among smokers, 5-year absolute risk of participants increased as the genetic risk increased. Hence, it was recommended that people at high genetic risk should start screening earlier. For the highest genetic risk populations (the top 1% of PRS), the start age might be changed to 50 years old. If the start age remained at 55-year-old, the smoking dose should be set lowered in high genetic risk populations. For the highest genetic risk populations, they should be included in lung cancer screening regardless of the cumulative smoking exposure. Among nonsmokers, it was also valuable to screen people with high genetic risk, considering the start age of 62 for the highest genetic risk populations and 74 for the lowest genetic risk populations (the bottom 5% of PRS). Conclusions: PRS-19 can be effectively used in developing lung cancer screening program for individualized prevention in China. For smokers with high genetic risk, the recommended starting age and smoking dose could be lowered for lung cancer screening, and non-smokers with high genetic risk could also be included in the screening programs.

Risk of liver disease in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis receiving methotrexate: A population-based study

Patients with psoriatic disease may be more susceptible to methotrexate hepatotoxicity than those with rheumatoid arthritis (RA); however, direct evidence supporting this notion is lacking. To compare liver disease risk among patients with psoriasis (PsO), psoriatic arthritis (PsA), or RA receiving methotrexate. In a population-based cohort study, Danish individuals with PsO, PsA, or RA receiving methotrexate between 1997 and 2015 were compared according to 4 disease outcomes: mild liver disease, moderate-to-severe liver disease, cirrhosis, and cirrhosis-related hospitalization. Among 5687, 6520, and 28,030 patients with PsO, PsA, and RA, respectively, the incidence rate of any liver disease was greatest for PsO, followed by PsA, and lowest for RA. Compared with patients with RA, patients with PsO were 1.6-3.4 times more likely to develop at least one of the liver disease outcomes, whereas those with PsA were 1.3-1.6 times more likely to develop mild liver disease and cirrhosis after adjusting for demographics, smoking, alcohol use, comorbidities, and methotrexate dose. Confounding due to unmeasured variables, misclassification, and surveillance bias. PsO, PsA, and RA differentially influence liver disease risk in the setting of methotrexate use independent of other major risk factors. More conservative monitoring should be considered in patients receiving methotrexate for psoriatic disease, particularly in PsO patients.

Effect of metformin and insulin vs. placebo and insulin on whole body composition in overweight patients with type 2 diabetes: a randomized placebo-controlled trial.

Glucose-lowering medications affect body composition. We assessed the long-term effects of metformin compared with placebo on whole body bone and body composition measures in patients with type 2 diabetes mellitus. This was a sub-study of the Copenhagen Insulin and Metformin Therapy trial, which was a double-blinded randomized placebo-controlled trial assessing 18-month treatment with metformin compared with placebo, in combination with different insulin regimens in patients with type 2 diabetes mellitus (T2DM). The sub-study evaluates the effects on bone mineral content (BMC), density (BMD), and body composition from whole body dual-energy X-ray absorptiometry (DXA) scans which were assessed at baseline and after 18 months. Metformin had a small, but positive, (p < 0.05) effect on subtotal, appendicular, and legs BMC and BMD compared with placebo. After adjustment for sex, age, vitamin D, smoking, BMI, T2DM duration, HbA1c, and insulin dose, the effects on appendicular BMC and BMD persisted (p < 0.05 for both). The changes in appendicular BMC and BMD corresponded approximately to a 0.7% and 0.5% increase in the metformin group and 0.4% and 0.4% decrease in the placebo group, respectively. These effects were mostly driven by an increase in BMC and BMD in the legs and a loss of BMC and BMD in the arms. During 18 months, all participants increased in weight, fat mass (FM), FM%, and lean mass (LM), but decreased in LM%. The metformin group increased less in weight (subtotal weight (weight-head) - 2.4 [- 3.5, - 1.4] kg, p value < 0.001) and FM (- 1.5 [- 2.3, - 0.8] kg, p value < 0.001) and decreased less in LM% (0.6 [0.2, 1.1] %, p value < 0.001) compared with the placebo group. Metformin treatment had a small positive effect on BMC and BMD in the peripheral skeleton and reduced weight gain compared with placebo in insulin-treated patients with T2DM.