Tobacco use, self-reported professional dental cleaning habits, and lung adenocarcinoma diagnosis are associated with bronchial and lung microbiome alpha diversity.

RATIONALE: The lung microbiome is an inflammatory stimulus whose role in the development of lung malignancies is incompletely understood. We hypothesized that the lung microbiome associates with multiple clinical factors, including the presence of a lung malignancy. OBJECTIVES: To assess associations between the upper and lower airway microbiome and multiple clinical factors including lung malignancy. METHODS: We conducted a prospective cohort study of upper and lower airway microbiome samples from 44 subjects undergoing lung lobectomy for suspected or confirmed lung cancer. Subjects provided oral (2), induced sputum, nasopharyngeal, bronchial, and lung tissue (3) samples. Pathologic diagnosis, age, tobacco use, dental care history, lung function, and inhaled corticosteroid use were associated with upper and lower airway microbiome findings. MEASUREMENTS AND MAIN RESULTS: Older age was associated with greater Simpson diversity in the oral and nasopharyngeal sites (p = 0.022 and p = 0.019, respectively). Current tobacco use was associated with greater lung and bronchus Simpson diversity (p < 0.0001). Self-reported last profession dental cleaning more than 6 months prior (vs. 6 or fewer months prior) was associated with lower lung and bronchus Simpson diversity (p < 0.0001). Diagnosis of a lung adenocarcinoma (vs. other pathologic findings) was associated with lower bronchus and lung Simpson diversity (p = 0.024). Last professional dental cleaning, dichotomized as ≤ 6 months vs. >6 months prior, was associated with clustering among lung samples (p = 0.027, R2 = 0.016). Current tobacco use was associated with greater abundance of pulmonary pathogens Mycoplasmoides and Haemophilus in lower airway samples. Self-reported professional dental cleaning ≤ 6 months prior (vs. >6 months prior) was associated with greater bronchial Actinomyces and lung Streptococcus abundance. Lung adenocarcinoma (vs. no lung adenocarcinoma) was associated with lower Lawsonella abundance in lung samples. Inhaled corticosteroid use was associated with greater abundance of Haemophilus among oral samples and greater Staphylococcus among lung samples. CONCLUSIONS: Current tobacco use, recent dental cleaning, and a diagnosis of adenocarcinoma are associated with lung and bronchial microbiome α-diversity, composition (ß-diversity), and the abundance of several respiratory pathogens. These findings suggest that modifiable habits (tobacco use and dental care) may influence the lower airway microbiome. Larger controlled studies to investigate these potential associations are warranted.

Effect of tobacco use on Zenker's diverticulotomy outcomes.

OBJECTIVE: To compare clinical outcomes in patients with and without history of tobacco use who underwent Zenker's diverticulotomy (ZD). STUDY DESIGN: Single institution retrospective review. SETTING: Tertiary care academic hospital. METHODS: A retrospective review of patients who underwent ZD via an open stapler, rigid endoscopic CO2 laser, stapler or harmonic scalpel, and flexible endoscopic technique from January 2006 to December 2020 was performed. Data were abstracted for patient demographics, diverticular features, and rates of adverse events and symptomatic recurrence. RESULTS: Out of 424 patients, 146 (34.4 %) had a history of tobacco use: 126 (29.7 %) were former smokers, and 20 (4.7 %) were active smokers. In univariable cross-sectional analyses, the likelihood of postoperative bleeding, perforation, emergency department visits, unplanned readmission, or recurrence did not demonstrate an association with tobacco use history even after adjustment for age, sex, and surgical approach. Similarly, in Cox Proportional Hazards regression, tobacco use was not associated with an increased risk of recurrence, even after correcting for age, sex, and type of surgery. The median time to recurrence observed in our cohort was 11.5 years amongst non-smokers, 8.7 years amongst former smokers, and 1.2 years amongst active smokers (p = 0.94). CONCLUSIONS: There were no significant differences in post-operative adverse events or frequency of recurrence of ZD between active, former, and non-smokers. Although underpowered and not statistically significant, median time to recurrence appears to be shorter in smokers when compared with former and non-smokers following surgery.

The association between smoking and smokeless tobacco use with dental caries among Pakistani patients.

BACKGROUND: Tobacco use is widely recognised as a significant risk factor for oral cancer and periodontal diseases. However, the relationship between various types of tobacco use and dental caries has been inconsistent. This study aimed to determine the association between smoking and smokeless tobacco and dental caries among patients in a tertiary care hospital in Quetta, Pakistan. METHODS: This cross-sectional study was conducted from November 2020 to March 2021 among patients in a tertiary care hospital in Quetta, Pakistan. Oral examinations and interviews were performed according to the WHO Oral Health Survey basic methods (5th edition) to determine dental caries status, tobacco use, and oral health behaviours. The odds ratio and binary logistic regression were analysed to assess the association between the types (smoking tobacco, smokeless tobacco, and use of both types), duration, and frequency of tobacco use and high caries level (DMFT ≥ 5). RESULTS: Four hundred participants aged 18-65 were included, and 67.8% were tobacco users. Use of both smoking and smokeless tobacco (aOR = 14.7, 95%CI = 1.87-115.96, p = 0.011), smokeless tobacco only (aOR = 5.90, 95%CI = 1.89-18.37, p = 0.002), and smoking only (aOR = 2.18, 95%CI = 1.23-3.88, p = 0.008) were associated with significantly increased risk of high caries. Using tobacco for longer periods and more frequently daily also significantly increases the risk of high caries. CONCLUSION: Smoking and smokeless tobacco are significantly associated with high dental caries after adjusting for other factors. Due to the high severity of dental caries and the high prevalence of tobacco use among Pakistani patients in this study, it is highly recommended to strengthen policies aimed at reducing tobacco usage, including smokeless forms.

Hypertension in Low- and Middle-Income Countries.

In recent decades low- and middle-income countries (LMICs) have been witnessing a significant shift toward raised blood pressure; yet in LMICs, only 1 in 3 are aware of their hypertension status, and ≈8% have their blood pressure controlled. This rising burden widens the inequality gap, contributes to massive economic hardships of patients and carers, and increases costs to the health system, facing challenges such as low physician-to-patient ratios and lack of access to medicines. Established risk factors include unhealthy diet (high salt and low fruit and vegetable intake), physical inactivity, tobacco and alcohol use, and obesity. Emerging risk factors include pollution (air, water, noise, and light), urbanization, and a loss of green space. Risk factors that require further in-depth research are low birth weight and social and commercial determinants of health. Global actions include the HEARTS technical package and the push for universal health care. Promising research efforts highlight that successful interventions are feasible in LMICs. These include creation of health-promoting environments by introducing salt-reduction policies and sugar and alcohol tax; implementing cost-effective screening and simplified treatment protocols to mitigate treatment inertia; pooled procurement of low-cost single-pill combination therapy to improve adherence; increasing access to telehealth and mHealth (mobile health); and training health care staff, including community health workers, to strengthen team-based care. As the blood pressure trajectory continues creeping upward in LMICs, contextual research on effective, safe, and cost-effective interventions is urgent. New emergent risk factors require novel solutions. Lowering blood pressure in LMICs requires urgent global political and scientific priority and action.

Alteration of oral bacteriome of smokeless tobacco users and their association with oral cancer.

Smokeless tobacco (SLT) is certainly one of the major risk factors associated with oral cancer. Disruption of oral microbiota-host homeostasis contributes to the progression of oral cancer. Here, we profiled SLT users' oral bacterial composition and inferred their functions by sequencing 16S rDNA V3-V4 region and PICRUSt2, respectively. Oral bacteriome of SLT users (with or without oral premalignant lesions), SLT with alcohol co-users, and non-SLT consumers were compared. Oral bacteriome is shaped primarily by SLT use and the incidence of oral premalignant lesions (OPL). A significantly increased bacterial α-diversity was monitored in SLT users with OPL compared to in SLT users without OPL and non-users, whereas ß-diversity was significantly explained by OPL status. Overrepresented genera were Prevotella, Fusobacterium, Veillonella, Haemophilus, Capnocytophaga, and Leptotrichia in SLT users having OPL. LEfSe analysis identified 16 genera as a biomarker that were differentially abundant in SLT users having OPL. The functional prediction of genes significantly increased for several metabolic pathways, more importantly, were nitrogen metabolism, nucleotide metabolism, energy metabolism, and biosynthesis/biodegradation of secondary metabolites in SLT users having OPL. Furthermore, HPV-16 and EBV, but not HPV-18, were considerably connected with the SLT users having OPL. Overall, this study provides evidence that SLT utilization and OPL development are associated with oral bacteriome dysbiosis indicating the enrichment of bacterial species known for their contribution to oral carcinogenesis. Therefore, delineating the cancer-inducing bacterial population in SLT users will facilitate the future development of microbiome-targeted therapies. KEY POINTS: • SLT consumption significantly elevates oral bacterial diversity. • Prevalent significant genera are Prevotella, Veillonella, and Haemophilus in SLT users with OPL. • SLT promotes the occurrence of the cancer-inducing bacterial population.

Smokeless tobacco use and public health nutrition: a global systematic review.

OBJECTIVE: Tobacco consumption among low- and middle-income countries where food insecurity remains a challenge poses several concerns. This review examines the available global evidence linking smokeless tobacco (SLT) use with public health nutrition and its implications. DESIGN: Systematic review of articles extracted from PubMed and Scopus from January 2000 to December 2020. SETTING: Included studies that demonstrated the relationship between SLT and nutrition-related factors, that is, BMI, malnutrition, anaemia, poor birth outcomes and metabolic disorders. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines have been followed to conduct the systematic evidence review. PARTICIPANTS: A total of thirty-four studies were finally used in the systematic review, which included cross-sectional (thirty-one) and cohort (three). RESULTS: SLT use has a huge impact on body weight, alteration in taste, poor oral health, and consumption of fruits and vegetables leading to malnutrition. Maternal use of SLT not only leads to anaemia but also hampers birth outcomes. Increased risk of metabolic syndrome and gallstone disease among SLT users are also well documented in the studies. CONCLUSION: The review highlights the linkages between SLT usage and poor nutritional outcomes. Tobacco control efforts should be convergent with public health nutrition to achieve overall health benefits. Attention is also required to explore suitable mechanisms for SLT cessation combined with enhancing food and nutrition security at the community level in sync with investments in public health nutrition intervention.

Tobacco and Cannabis Use Have a Synergistic Association on Infection Risk Following Total Knee Arthroplasty.

BACKGROUND: Studies suggest an increase in the number of combined users of tobacco and cannabis. Therefore, we specifically assessed tobacco, cannabis, and combined users who underwent primary total knee arthroplasty (TKA) to determine 90-day to 2-year: (1) odds of periprosthetic joint infection; (2) odds of revision; and (3) medical complications. METHODS: We queried a national, all payer database of patients undergoing primary TKA between 2010 and 2020. Patients were stratified according to current use of tobacco products (n = 30,000), cannabis (n = 400), or a combination (n = 3,526). These were defined according to International Classification of Disease codes, Ninth and Tenth Editions. Patients were tracked from the 2 years before TKA through 2 years afterwards. A fourth group of TKA recipients who did not have tobacco nor cannabis use was used as a matching cohort. Periprosthetic joint infections (PJIs), revisions, and other medical/surgical complications from 90 days through 2 years were evaluated between these cohorts using bivariate analyses. Multivariate analyses assessed independent risk factors for PJI at 90 days through 2 years, adjusted for patient demographics and health metrics. RESULTS: Combined tobacco and cannabis use were associated with the highest rates of PJI following TKA. The odds of 90-day PJI risk among cannabis, tobacco, and combined users was 1.60, 2.14, and 3.39, respectively, as compared to the matched cohort (P < .001). Co-users had the highest and significantly increased revision odds at 2 years following TKA (odds ratio = 1.52, 95% confidence interval, 1.15 to 2.00). At 1 and 2 years following TKA, cannabis, tobacco, and co-users had higher rates of myocardial infarctions, respiratory failures, surgical site infections, and manipulations under anesthesia when compared to the matched cohort (all P < .001). CONCLUSION: Tobacco and cannabis use before primary TKA demonstrated a synergistic association on PJI risk from 90 days through 2 years. Although the harms of tobacco use are well-known, this additional knowledge about cannabis should be incorporated in the shared decision-making discussions in the pre-operative setting to best prepare for expected risks following primary TKA.

Smokeless Tobacco Use is Associated With Worse Outcomes Following Total Knee Arthroplasty.

BACKGROUND: Studies have demonstrated increased complication risk after total knee arthroplasty (TKA) in patients who smoke cigarettes, but it is unclear if smokeless tobacco use confers a similar impact. The purpose of this study was to (1) evaluate rates of postoperative complications after TKA in smokeless tobacco users and smokers as compared to matched controls, and (2) compare rates of postoperative complications in smokeless tobacco users versus smokers to determine if one is associated with significantly higher rates of postoperative complications. METHODS: A retrospective cohort study was conducted using a national database. For patients who underwent primary TKA, smokeless tobacco users (n = 1,535) and smokers (n = 28,953) were matched at a 1:4 with controls (n = 6,140 and 115,812, respectively), and smokeless tobacco users (n = 1,481) were matched at a 1:4 with smokers (n = 5,924). Rates of joint complications within 2 years and medical complications within 90 days postoperatively were compared using multivariable logistic regressions. RESULTS: After primary TKA, compared to controls, smokeless tobacco users demonstrated significantly higher rates of aseptic loosening/mechanical failure within 2 years, longer lengths of stay, and higher rates of urinary tract infection, pneumonia, deep vein thrombosis, and acute kidney injury within 90 days. Compared to smokers, smokeless tobacco users demonstrated significantly lower rates of aseptic revision and lower rates of wound disruption. CONCLUSION: Smokeless tobacco use is associated with higher rates of both medical and joint complications following primary TKA. However, smoking is associated with higher risk for complications than smokeless tobacco use. LEVEL OF EVIDENCE: Level III.

Analysis of Complications in Patients With a History of Cannabis Use and Tobacco Use Undergoing Implant-Based Breast Reconstruction.

BACKGROUND: There is limited information regarding the perioperative effects of marijuana in breast reconstructive surgeries. OBJECTIVES: The objective of this study was to explore the association between a history of cannabis use and postoperative complications in the setting of implant-based breast reconstruction. METHODS: Two databases, TriNetX and PearlDiver, were queried for patients undergoing implant-based breast reconstruction. Patients were divided into 4 groups based on active ICD-10 diagnostic codes: (1) cannabis use only, (2) tobacco use only, (3) cannabis and tobacco use, and (4) neither cannabis nor tobacco use. Associations with postoperative complications were analyzed with a logistic regression test. RESULTS: TriNetX search revealed that 327 patients had an active diagnosis of cannabis use only and 1118 had an active diagnosis of tobacco use only. Patients in the cannabis only cohort had a significantly increased risk of developing surgical site infection. Patients in the tobacco only cohort had significantly increased risk of developing wound dehiscence, need for debridement, and surgical site infection. The PearlDiver search included 472 patients who had an active diagnosis of both cannabis and tobacco use and 17,361 patients with a diagnosis of tobacco use only. Patients with a diagnosis of cannabis and tobacco use had a significantly increased risk of developing postoperative complications including surgical site infection, wound dehiscence, need for incision and drainage, and debridement. CONCLUSIONS: Patients undergoing implant-based breast reconstruction with an active diagnosis of cannabis with or without tobacco use were at increased risk of developing postoperative complications, and the risk was even higher in patients using both tobacco and cannabis.

Combined Associations of Changes in Noncombustible Nicotine or Tobacco Product and Combustible Cigarette Use Habits With Subsequent Short-Term Cardiovascular Disease Risk Among South Korean Men: A Nationwide Cohort Study.

BACKGROUND: The associations of changes in noncombustible nicotine or tobacco product (NNTP) and combustible cigarette (CC) use habits with subsequent cardiovascular disease (CVD) risk are still unclear. METHODS: The study population consisted of 5 159 538 adult men who underwent health screening examinations during both the first (2014-2015) and second (2018) health screening periods from the Korean National Health Insurance Service database. All participants were divided into continual CC-only smokers, CC and NNTP users, recent (<5 years) CC quitters without NNTP use, recent CC quitters with NNTP use, long-term (≥5 years) CC quitters without NNTP use, long-term CC quitters with NNTP use, and never smokers. Propensity score matching analysis was conducted to further compare CVD risk among CC quitters according to NNTP use. Starting from the second health screening date, participants were followed up until the date of CVD event, death, or December 31, 2019, whichever came earliest. Multivariable Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% CIs for CVD risk according to changes in NNTP and CC smoking habits. RESULTS: Compared with continual CC-only smokers, CC and NNTP users (aHR, 0.83 [95% CI, 0.79-0.88]) and initial CC smokers who quit CCs and switched to NNTP use only (recent CC quitters with NNTP use, aHR, 0.81 [95% CI, 0.78-0.84]) had lower risk for CVD. After propensity score matching, recent CC quitters with NNTP use (aHR, 1.31 [95% CI, 1.01-1.70]) had higher risk for CVD than recent CC quitters without NNTP use. Similarly, compared with long-term CC quitters without NNTP use, long-term CC quitters with NNTP use (aHR, 1.70 [95% CI, 1.07-2.72]) had higher CVD risk. CONCLUSIONS: Switching to NNTP use among initial CC smokers was associated with lower CVD risk than continued CC smoking. On CC cessation, NNTP use was associated with higher CVD risk than CC quitting without NNTPs. Compared with CC smokers who quit without NNTP use, CC quitters who use NNTPs may be at higher future CVD risk.

Potential Risk Factors of Smokeless Tobacco Consumption Among Adolescents in South India.

INTRODUCTION: Although most of the disease burden internationally is due to tobacco smoking, smokeless tobacco (SLT) use contributed to an estimated 76 000 deaths in 2017. We have studied the potential risk factors for SLT use among adolescents in South India. METHODS: A cross-sectional questionnaire survey of all students in grades 6-8 in schools in the Udupi district of Karnataka State ascertained SLT use status and potential determinants of SLT uptake. Ever SLT use was defined as any reported consumption of any SLT products, currently or at any time in the past. Independent effects on ever SLT use status were estimated using multiple logistic regression. RESULTS: Of 46 706 students from 914 participating schools, 39 282 (84.1%) provided questionnaire responses sufficiently complete for analysis. Ever SLT use was reported by 775 (2.0%) participants and in a mutually adjusted model was significantly related to age, male sex, family use, or friend's use of SLT, low socioeconomic status, high rebelliousness, and low self-esteem. After controlling for these effects, the odds of ever-SLT use were significantly higher among students who had least awareness of the harmful effects of tobacco use (odds ratio 3.7, 95% confidence interval [2.9, 4.7]) and significantly lower among those not exposed to tobacco advertising (odds ratio 0.7, 95% confidence interval [0.5, 0.8]). CONCLUSIONS: The prevalence of SLT use among children in Karnataka is relatively low when compared with other studies in India. The significant potential risk factors of SLT use include low awareness of the harmful effects of tobacco and tobacco control policies and exposure to tobacco advertising. IMPLICATIONS: The prevalence of SLT use among school going adolescents in South India is relatively low. The potential risk factors for SLT use among adolescents in southern India are similar to those for smoked tobacco. It includes age, male gender, family or friend's use of SLT, low socioeconomic status, high rebelliousness, low self-esteem, exposure to tobacco advertisement and least awareness about the harmful effects of tobacco and of tobacco control policies. The present study lays emphasis regarding creating awareness about tobacco harms and control policies for further reducing tobacco use among adolescents.

Estimates of major non-communicable disease risk factors for India, 2010 & 2015: A summary of evidence.

Background & objectives: The National Monitoring Framework for the prevention and control of NCDs in India has set targets for reduction of risk factors relative to the measure recorded in 2010. Estimates for 2010 and 2015 were established using meta-analyses in the absence of a national risk factor survey till 2017. Methods: We searched national survey reports and also articles published in English from India between 2008 and 2017 in PubMed, Google Scholar and Cochrane review databases for specific risk factors among 18-69 yr Indians. Quality of studies was evaluated using Joanna-Briggs tool, but all studies were included in analyses. Estimates for each of the eight strata by age, gender and place of residence, respectively, were generated. MetaXL was used to calculate the pooled estimate for 2010 and 2015 using a random effects model. Strata-specific estimates were combined to arrive at national estimate using population weight of each stratum. The credibility of the estimates was determined using four parameters - average Briggs score; representativeness of the contributing studies and precision and stability of the estimates. Results: The estimates [95% confidence interval (CI)] for 2010 for different risk factors were as follows: current alcohol use, 15.7 per cent (13.2-18.2); current tobacco use, 27 per cent (21.4-32.6); household solid fuel use, 61.5 per cent (50.2-72.5); physical inactivity, 44.2 per cent (37.8-50.6); obesity, seven per cent (3.8-10.2) and raised blood pressure, 20.2 per cent (18.4-22.1). In 2015, compared to 2010, tobacco use showed a relative decline of 18 per cent, household solid fuel use of nine per cent and physical inactivity of 15 per cent. The estimates were stable for alcohol use, raised blood pressure and obesity between 2010 and 2015. All estimates varied between moderate and high degrees of credibility. Interpretation & conclusions: The estimates are consistent with other available estimates and with current national-level initiatives focused on tobacco control and improving access to clean fuel. These estimates can be used to monitor progress on non-communicable disease risk factor targets for India.

Complications after high tibial osteotomy and distal femoral osteotomy are associated with increasing medical comorbidities and tobacco use.

PURPOSE: The purpose of this study was to assess complications, reoperations, and their risk factors at 90 days and 2 years after high tibial osteotomy (HTO) and distal femoral osteotomy (DFO) in a national cohort. METHODS: The PearlDiver Mariner Dataset was queried using International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes for HTO and DFO, complications, and subsequent surgery. Minimum follow-up was 2 years and complications were assessed at 90 days and 2 years. Hospital readmission in the first 90 days was also assessed. Univariate and multiple logistic regression were utilized to identify risk factors for complications and re-operation. RESULTS: The 90-day and 2-year complication rates after HTO (n = 1780) were 11.6% and 31.7%, compared to 21.5% (p < 0.0001) and 41.5% (p = 0.0001) after DFO (n = 446). Infection was the most frequent early (90-day) complication for both HTO and DFO cohorts, while hardware problems were most common at 2 years. Increasing Elixhauser Comorbidity Index (ECI) was associated with increased odds of infection, readmission, and hardware-associated complications in both cohorts. Gender and tobacco use were also associated with various complications after HTO. At 2 years, 23.7% of HTO patients and 26.2% of DFO patients had undergone subsequent surgery. Hardware removal occurred in 16.4% of HTO and 18.4% of DFO patients (n.s.), while 4.5% of HTO and 5.2% of DFO patients underwent total knee arthroplasty (TKA) within 2 years (n.s.). CONCLUSION: HTO and DFO have substantial complication rates in the short and mid term, with a higher rate of overall complications observed after DFO as compared to the HTO cohort. After both procedures, roughly one quarter of patients will undergo subsequent surgery within 2 years. Patients with tobacco use and numerous medical co-morbidities may not be optimal candidates due to increased complication rates. Elixhauser Comorbidity Index (ECI) may be an useful tool for risk assessment prior to surgery. LEVEL OF EVIDENCE: Retrospective cohort study, III.

Chronic mechanical irritation enhances the effect of tobacco and alcohol on the risk of oral squamous cell carcinoma: a case-control study in Argentina.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is a multifactorial disease. The individual effect of each risk factor for OSCC may be conditioned by the frequency of other factors. The objective of this study was to identify the association between chronic mechanical irritation (CMI) and OSCC and to analyse the influence of CMI on other important risk factors for OSCC. MATERIALS AND METHODS: A prospective and age/sex-matched case-control study was performed in two institutions from Argentina between 2009 and 2019, with consecutive and newly diagnosed OSCC. The frequencies of tobacco, alcohol, and CMI were analysed using conditional logistic regression. Cumulative tobacco consumption and the presence of CMI were analysed using the Mann-Whitney test. RESULTS: CMI and OSCC were associated with an OR of 7.02 (95% CI 3.57-13.78, p < 0.001). The combination of CMI and alcohol demonstrated the highest risk of OSCC (OR 53.83, CI 95% 8.04-360, p < 0.0001), followed by the combination of CMI, tobacco, and alcohol (OR 48.06, CI 95% 8.47-272, p < 0.0001). The combination of CMI and tobacco was also significant (OR 5.61, CI 95% 1.07-29.54, p = 0.042). Patients with CMI developed OSCC with less cumulative tobacco use compared with those without CMI. CONCLUSION: CMI is an independent risk factor for OSCC, and it could act as a risk modifier among tobacco and alcohol users having an enhancing effect. CLINICAL RELEVANCE: Elimination of CMI could decrease the risk of OSCC.

The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions.

Drug addiction causes constant serious health, social, and economic burden within the human society. The current drug dependence pharmacotherapies, particularly relapse prevention, remain limited, unsatisfactory, unreliable for opioids and tobacco, and even symptomatic for stimulants and cannabinoids, thus, new more effective treatment strategies are researched. The antagonism of the growth hormone secretagogue receptor type A (GHS-R1A) has been recently proposed as a novel alcohol addiction treatment strategy, and it has been intensively studied in experimental models of other addictive drugs, such as nicotine, stimulants, opioids and cannabinoids. The role of ghrelin signaling in these drugs effects has also been investigated. The present review aims to provide a comprehensive overview of preclinical and clinical studies focused on ghrelin's/GHS-R1A possible involvement in these nonalcohol addictive drugs reinforcing effects and addiction. Although the investigation is still in its early stage, majority of the existing reviewed experimental results from rodents with the addition of few human studies, that searched correlations between the genetic variations of the ghrelin signaling or the ghrelin blood content with the addictive drugs effects, have indicated the importance of the ghrelin's/GHS-R1As involvement in the nonalcohol abused drugs pro-addictive effects. Further research is necessary to elucidate the exact involved mechanisms and to verify the future potential utilization and safety of the GHS-R1A antagonism use for these drug addiction therapies, particularly for reducing the risk of relapse.

PATH to understanding cannabis and nicotine initiation and co-use among emerging adults.

OBJECTIVES: The purpose of this study was to describe the characteristics and age of initiation of nicotine and cannabis use, with a particular focus on the emerging adult period (ages 18-24 years) and concurrent use of nicotine with cannabis. DESIGN: A secondary analysis of Population Assessment of Tobacco and Health (PATH). SAMPLE: 32,078 participants from a nationally representative study of tobacco use and health outcomes. MEASUREMENT: Variables of interest included ever use, regular use and age of initiation (first-time use) of nicotine (including tobacco) and/or cannabis and selected demographic factors. RESULTS: Ever-use of nicotine was associated with a 13-fold increase in the likelihood of having ever used cannabis. Among those who reported cannabis use, 96.4% had also used nicotine. While initiation in adolescence was most common, 27.1% of those who use nicotine and 34.9% of those who use cannabis initiated during emerging adulthood. Among regular users of nicotine, 41.5% began regular use in emerging adulthood. CONCLUSIONS: These findings underscore the continued susceptibility of emerging adults to initiation of these substances. Co-use of nicotine and cannabis is an understudied phenomenon in emerging adults with significant potential to cause harm and should be a public health priority.

Clinicopathological Evaluation of Tobacco-related Oral Mucosal Lesions.

AIM: To clinically evaluate the nature of precancerous and cancerous lesions associated with tobacco consumption habit and to correlate clinical profile with the histopathological findings of clinically suspected precancerous and cancerous lesions. MATERIALS AND METHODS: These included the examination of patients who visited the outpatient department (OPD) of the institute that includes 1,500 patients who had tobacco chewing habits were classified into the following two groups according to their characteristics. The study group comprised 270 patients, of which 170 gave consent for biopsy and 100 patients who not gave consent were counseled for tobacco cessation. RESULTS: Among 270 patients, the highest number of patients, 146 (54.07%) patients, were found to be smokeless tobacco consumers followed by 65 (24.07%) patients who were smoked tobacco consumers while 59 (21.85%) patients were found to have both the habits. Wide variation was noted in duration and frequency of habit. Most prevalent site was the buccal mucosa affected in 138 (51.11%) patients who consumed both smoked as well as smokeless tobacco. And on clinical examination, 138 (51%) patients had leukoplakia followed by 54 (20%) patients with oral squamous cell carcinoma and 40 (15%) patients with oral submucous fibrosis (OSMF). Other patients were tobacco pouch keratosis 17 (6%), smoker's melanosis 8 (3%), smoker's palate 7 (3%), and erythroplakia 6 (2%). The patients who gave consent (170 patients) were evaluated histopathologically to correlate with clinical findings. CONCLUSION: Tobacco-related oral lesions are also high, which brings an alarming signal toward the development of cancer. Our contribution as healthcare providers can be made by conducting more oral health education programs and educating the general population about the adverse effects of tobacco. The appropriate clinical assessment and categorization of all these lesions aided us in motivating patients to undergo necessary treatments and also to discontinue their habits in order to prevent deterioration of their conditions. CLINICAL SIGNIFICANCE: Set up de-addiction centers in dental colleges and help tobacco users in discontinuing their habits. Interestingly, this study also served as a mirror for those patients who were unaware of the lesions they were giving abode to in their oral cavities.

Unraveling most abundant mutational signatures in head and neck cancer.

Genomic alterations are a driving force in the multistep process of head and neck cancer (HNC) and result from the interaction of exogenous environmental exposures and endogenous cellular processes. Each of these processes leaves a characteristic pattern of mutations on the tumor genome providing the unique opportunity to decipher specific signatures of mutational processes operative during HNC pathogenesis and to address their prognostic value. Computational analysis of whole exome sequencing data of the HIPO-HNC (Heidelberg Center for Personalized Oncology-head and neck cancer) (n = 83) and TCGA-HNSC (The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma) (n = 506) cohorts revealed five common mutational signatures (Catalogue of Somatic Mutations in Cancer [COSMIC] Signatures 1, 2, 3, 13 and 16) and demonstrated their significant association with etiological risk factors (tobacco, alcohol and HPV16). Unsupervised hierarchical clustering identified four clusters (A, B, C1 and C2) of which Subcluster C2 was enriched for cases with a higher frequency of signature 16 mutations. Tumors of Subcluster C2 had significantly lower p16INK4A expression accompanied by homozygous CDKN2A deletion in almost one half of cases. Survival analysis revealed an unfavorable prognosis for patients with tumors characterized by a higher mutation burden attributed to signature 16 as well as cases in Subcluster C2. Finally, a LASSO-Cox regression model was applied to prioritize clinically relevant signatures and to establish a prognostic risk score for head and neck squamous cell carcinoma patients. In conclusion, our study provides a proof of concept that computational analysis of somatic mutational signatures is not only a powerful tool to decipher environmental and intrinsic processes in the pathogenesis of HNC, but could also pave the way to establish reliable prognostic patterns.

Pathfinders in oncology from the time the causal relation between tobacco use and lung cancer was established to publication of the first Cancer Staging Manual by the American Joint Committee on Cancer.

During the period from 1962 to 1977, several antigens, notably carcinoembryonic antigen and prostate-specific antigen, were discovered and entered clinical use. Ultrasonography, positron emission tomography scanning, and magnetic resonance imaging were introduced, and adjuvant radiation and chemotherapy after limited surgery became routine procedures. Radioimmunoassay and immunohistochemistry techniques were standardized. The announcement in England and the United States that tobacco is a potent lung carcinogen was long delayed, important news. The US Cancer Act of 1971 made it possible to experiment with newly discovered drugs, transfer promising therapeutic agents from the laboratory to the clinic, and finance randomized clinical trials. Oncologists achieved a series of successes with combination chemotherapy in childhood cancers, adult lymphomas, and testis tumors. Clinical trials demonstrated that breast-conserving therapy is as effective as mastectomy. The discovery of retroviruses, reverse transcriptase, and vascular endothelial growth factor was coupled with learning about oncogenes. The 2-hit theory and the reciprocal translocation of chromosomes helped to solve some of the riddles of oncogenesis. The staging classification of cancers by the American Joint Committee on Cancer unified clinical and pathologic handling and prognostication of malignant tumors. The progress made in oncology between 1962 and 1977 came about through the dedicated work of many individuals. However, there were 9 pathfinders (3 medical oncologists, 2 surgeons, 1 medical nuclear physicist, 1 pediatrician geneticist, 1 hematologist geneticist, and 1 virologist) who, despite their diverse backgrounds, personalities, and interest, made extraordinary contributions to oncology.

The mutational landscape of early- and typical-onset oral tongue squamous cell carcinoma.

BACKGROUND: The incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing among younger birth cohorts. The etiology of early-onset OTSCC (diagnosed before the age of 50 years) and cancer driver genes remain largely unknown. METHODS: The Sequencing Consortium of Oral Tongue Cancer was established through the pooling of somatic mutation data of oral tongue cancer specimens (n = 227 [107 early-onset cases]) from 7 studies and The Cancer Genome Atlas. Somatic mutations at microsatellite loci and Catalog of Somatic Mutations in Cancer mutation signatures were identified. Cancer driver genes were identified with the MutSigCV and WITER algorithms. Mutation comparisons between early- and typical-onset OTSCC were evaluated via linear regression with adjustments for patient-related factors. RESULTS: Two novel driver genes (ATXN1 and CDC42EP1) and 5 previously reported driver genes (TP53, CDKN2A, CASP8, NOTCH1, and FAT1) were identified. Six recurrent mutations were identified, with 4 occurring in TP53. Early-onset OTSCC had significantly fewer nonsilent mutations even after adjustments for tobacco use. No associations of microsatellite locus mutations and mutation signatures with the age of OTSCC onset were observed. CONCLUSIONS: This international, multicenter consortium is the largest study to characterize the somatic mutational landscape of OTSCC and the first to suggest differences by age of onset. This study validates multiple previously identified OTSCC driver genes and proposes 2 novel cancer driver genes. In analyses by age, early-onset OTSCC had a significantly smaller somatic mutational burden that was not explained by differences in tobacco use. LAY SUMMARY: This study identifies 7 specific areas in the human genetic code that could be responsible for promoting the development of tongue cancer. Tongue cancer in young patients (under the age of 50 years) has fewer overall changes to the genetic code in comparison with tongue cancer in older patients, but the authors do not think that this is due to differences in smoking rates between the 2 groups. The cause of increasing cases of tongue cancer in young patients remains unclear.