Association Between Marijuana Use and Risk of Cancer: A Systematic Review and Meta-analysis.

Importance: Marijuana use is common and growing in the United States amid a trend toward legalization. Exposure to tobacco smoke is a well-described preventable cause of many cancers; the association of marijuana use with the development of cancer is not clear. Objective: To assess the association of marijuana use with cancer development. Data Sources: A search of PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library was conducted on June 11, 2018, and updated on April 30, 2019. A systematic review and meta-analysis of studies published from January 1, 1973, to April 30, 2019, and references of included studies were performed, with data analyzed from January 2 through October 4, 2019. Study Selection: English-language studies involving adult marijuana users and reporting cancer development. The search strategy contained the following 2 concepts linked together with the AND operator: marijuana OR marihuana OR tetrahydrocannabinol OR cannabinoid OR cannabis; AND cancer OR malignancy OR carcinoma OR tumor OR neoplasm. Data Extraction and Synthesis: Two reviewers independently reviewed titles, abstracts, and full-text articles; 3 reviewers independently assessed study characteristics and graded evidence strength by consensus. Main Outcomes and Measures: Rates of cancer in marijuana users, with ever use defined as at least 1 joint-year exposure (equivalent to 1 joint per day for 1 year), compared with nonusers. Meta-analysis was conducted if there were at least 2 studies of the same design addressing the same cancer without high risk of bias when heterogeneity was low to moderate for the following 4 cancers: lung, head and neck squamous cell carcinoma, oral squamous cell carcinoma, and testicular germ cell tumor (TGCT), with comparisons expressed as odds ratios (ORs) with 95% CIs. Results: Twenty-five English-language studies (19 case-control, 5 cohort, and 1 cross-sectional) were included; few studies (n = 2) were at low risk of bias. In pooled analysis of case-control studies, ever use of marijuana was not associated with head and neck squamous cell carcinoma or oral cancer. In pooled analysis of 3 case-control studies, more than 10 years of marijuana use (joint-years not reported) was associated with TGCT (OR, 1.36; 95% CI, 1.03-1.81; P = .03; I2 = 0%) and nonseminoma TGCT (OR, 1.85; 95% CI, 1.10-3.11; P = .04; I2 = 0%). Evaluations of ever use generally found no association with cancers, but exposure levels were low and poorly defined. Findings for lung cancer were mixed, confounded by few marijuana-only smokers, poor exposure assessment, and inadequate adjustment; meta-analysis was not performed for several outcomes. Conclusions and Relevance: Low-strength evidence suggests that smoking marijuana is associated with developing TGCT; its association with other cancers and the consequences of higher levels of use are unclear. Long-term studies in marijuana-only smokers would improve understanding of marijuana's association with lung, oral, and other cancers. Trial Registration: PROSPERO identifier: CRD42018102457.

Risk Prediction Tools to Improve Patient Selection for Carotid Endarterectomy Among Patients With Asymptomatic Carotid Stenosis.

Importance: Randomized clinical trials have demonstrated that patients with asymptomatic carotid stenosis are eligible for carotid endarterectomy (CEA) if the 30-day surgical complication rate is less than 3% and the patient's life expectancy is at least 5 years. Objective: To develop a risk prediction tool to improve patient selection for CEA among patients with asymptomatic carotid stenosis. Design, Setting, and Participants: In this cohort study, veterans 65 years and older who received both carotid imaging and CEA in the Veterans Administration between January 1, 2005, and December 31, 2009 (n = 2325) were followed up for 5 years. Data were analyzed from January 2005 to December 2015. A risk prediction tool (the Carotid Mortality Index [CMI]) based on 23 candidate variables identified in the literature was developed using Veterans Administration and Medicare data. A simpler model based on the number of 4 key comorbidities that were prevalent and strongly associated with 5-year mortality was also developed (any cancer in the past 5 years, chronic obstructive pulmonary disease, congestive heart failure, and chronic kidney disease [the 4C model]). Model performance was assessed using measures of discrimination (eg, area under the curve [AUC]) and calibration. Internal validation was performed by correcting for optimism using 500 bootstrapped samples. Main Outcome and Measure: Five-year mortality. Results: Among 2325 veterans, the mean (SD) age was 73.74 (5.92) years. The cohort was predominantly male (98.8%) and of white race/ethnicity (94.4%). Overall, 29.5% (n = 687) of patients died within 5 years of CEA. On the basis of a backward selection algorithm, 9 patient characteristics were selected (age, chronic kidney disease, diabetes, chronic obstructive pulmonary disease, any cancer diagnosis in the past 5 years, congestive heart failure, atrial fibrillation, remote stroke or transient ischemic attack, and body mass index) for the final logistic model, which yielded an optimism-corrected AUC of 0.687 for the CMI. The 4C model had slightly worse discrimination (AUC, 0.657) compared with the CMI model; however, the calibration curve was similar to the full model in most of the range of predicted probabilities. Conclusions and Relevance: According to results of this study, use of the CMI or the simpler 4C model may improve patient selection for CEA among patients with asymptomatic carotid stenosis.

Marijuana Use, Respiratory Symptoms, and Pulmonary Function: A Systematic Review and Meta-analysis.

Background: The health effects of smoking marijuana are not well-understood. Purpose: To examine the association between marijuana use and respiratory symptoms, pulmonary function, and obstructive lung disease among adolescents and adults. Data Sources: PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library from 1 January 1973 to 30 April 2018. Study Selection: Observational and interventional studies published in English that reported pulmonary outcomes of adolescents and adults who used marijuana. Data Extraction: Four reviewers independently extracted study characteristics and assessed risk of bias. Three reviewers assessed strength of evidence. Studies of similar design with low or moderate risk of bias and sufficient data were pooled. Data Synthesis: Twenty-two studies were included. A pooled analysis of 2 prospective studies showed that marijuana use was associated with an increased risk for cough (risk ratio [RR], 2.04 [95% CI, 1.02 to 4.06]) and sputum production (RR, 3.84 [CI, 1.62 to 9.07]). Pooled analysis of cross-sectional studies (1 low and 3 moderate risk of bias) showed that marijuana use was associated with cough (RR, 4.37 [CI, 1.71 to 11.19]), sputum production (RR, 3.40 [CI, 1.99 to 5.79]), wheezing (RR, 2.83 [CI, 1.89 to 4.23]), and dyspnea (RR, 1.56 [CI, 1.33 to 1.83]). Data on pulmonary function and obstructive lung disease were insufficient. Limitation: Few studies were at low risk of bias, marijuana exposure was limited in the population studied, cohorts were young overall, assessment of marijuana exposure was not uniform, and study designs varied. Conclusion: Low-strength evidence suggests that smoking marijuana is associated with cough, sputum production, and wheezing. Evidence on the association between marijuana use and obstructive lung disease and pulmonary function is insufficient. Primary Funding Source: None. (PROSPERO: CRD42017059224).

Associations Between Marijuana Use and Cardiovascular Risk Factors and Outcomes: A Systematic Review.

Background: Marijuana use is increasing in the United States, and its effect on cardiovascular health is unknown. Purpose: To review harms and benefits of marijuana use in relation to cardiovascular risk factors and clinical outcomes. Data Sources: PubMed, MEDLINE, EMBASE, PsycINFO, and the Cochrane Library between 1 January 1975 and 30 September 2017. Study Selection: Observational studies that were published in English, enrolled adults using any form of marijuana, and reported on vascular risk factors (hyperglycemia, diabetes, dyslipidemia, and obesity) or on outcomes (stroke, myocardial infarction, cardiovascular mortality, and all-cause mortality in cardiovascular cohorts). Data Extraction: Study characteristics and quality were assessed by 4 reviewers independently; strength of evidence for each outcome was graded by consensus. Data Synthesis: 13 and 11 studies examined associations between marijuana use and cardiovascular risk factors and clinical outcomes, respectively. Although 6 studies suggested a metabolic benefit from marijuana use, they were based on cross-sectional designs and were not supported by prospective studies. Evidence examining the effect of marijuana on diabetes, dyslipidemia, acute myocardial infarction, stroke, or cardiovascular and all-cause mortality was insufficient. Although the current literature includes several long-term prospective studies, they are limited by recall bias, inadequate exposure assessment, minimal marijuana exposure, and a predominance of low-risk cohorts. Limitation: Poor- or moderate-quality data, inadequate assessment of marijuana exposure and minimal exposure in the populations studied, and variation in study design. Conclusion: Evidence examining the effect of marijuana on cardiovascular risk factors and outcomes, including stroke and myocardial infarction, is insufficient. Primary Funding Source: National Heart, Lung, and Blood Institute. (PROSPERO: CRD42016051297).

Pioglitazone and metformin are equally effective in reduction of chemerin in patients with type 2 diabetes.

AIMS/INTRODUCTION: Chemerin, a novel member of the family of adipocytokines, has been shown to be associated with insulin resistance, as well as micro- and macrovascular complications of diabetes. We investigated the effects of pioglitazone and metformin, two commonly prescribed antidiabetic agents, on the reduction of serum chemerin concentrations. MATERIALS AND METHODS: In an open-labeled randomized clinical trial, 81 patients with newly diagnosed type 2 diabetes who were not taking antidiabetic medications were recruited. Patients were randomly assigned to either pioglitazone 30 mg daily or metformin 1,000 mg daily. Serum chemerin concentrations, indices of glycemic control, serum lipids concentrations, and anthropometric parameters were measured at baseline and after 3 months. RESULTS: Pioglitazone and metformin did not alter waist circumference, weight or body mass index after 3 months. In contrast, all indices of glycemia and insulin resistance improved substantially after 3 months' treatment with both medications (P < 0.01 in all analyses). There was a significant decrease in chemerin concentrations after 3 months in the pioglitazone group (P = 0.008). Similarly, metformin caused a significant drop in chemerin concentrations at week 12 (P = 0.015). When compared, metformin and pioglitazone proved to be equally effective in the alleviation of chemerin concentrations (P = 0.895, effect size: 0.1%). CONCLUSIONS: The present findings show that pioglitazone and metformin have comparable efficacy on serum chemerin concentrations, albeit through different mechanisms. Future studies need to focus on the clinical implications of lowered chemerin concentration on improvement of diabetes complications. This trial was registered with ClinicalTrials.gov (no. NCT01593371).

Comparative effects of pioglitazone and metformin on oxidative stress markers in newly diagnosed type 2 diabetes patients: a randomized clinical trial.

AIMS: Recent studies have suggested that pioglitazone exerts anti-oxidant properties which may countervail oxidative stress (OS). We aimed to elucidate the effects of pioglitazone on OS modulation and to compare its effects with metformin. METHODS: Data from the randomized clinical trial (registration no.NCT01521624) were used. Newly diagnosed type 2 diabetes patients were assigned to pioglitazone 30mg daily (n=30), metformin 1000mg daily (n=50), or no medication (n=49). Recommendations for exercise and dietary modifications were provided for three groups. Serum concentrations of advanced oxidation protein products(AOPP), advanced glycation end products(AGE), ferritin reducing ability of plasma(FRAP), and enzymatic activities of paraoxonase(PON), lecithin-cholesterol asyltransferase(LCAT), and lipoprotein lipase(LPL) were measured at baseline and after three months. RESULTS: In comparison with no medication, pioglitazone proved to be superior in OS amelioration (p<0.05 in all analyses). Compared with metformin, both medications were equally effective in decrement of AOPP and AGE, along with increment of PON (p=0.688, 0.140, and 0.273, respectively). FRAP concentrations increased significantly with metformin (p=0.012). On the other hand, pioglitazone yielded better efficacy in restoration of LCAT and LPL enzymatic activities (p=0.037, and <0.001, respectively). CONCLUSIONS: Similar to metformin, three months treatment with Pioglitazone is beneficial in terms of OS alleviation and anti-oxidant capacity restoration.

Fistula formation between the right and left main bronchus caused by endobronchial tuberculosis.

The prevalence of endobronchial tuberculosis (EBTB) in patients with active tuberculosis is about 10% to 40%. The most common complication of EBTB is bronchial stenosis. Fistula formation by pulmonary tuberculosis is a very rare complication and is most commonly bronchopleural. The authors present a 53-year-old woman presented with chronic cough and abnormality in chest computed tomography scan. According to chest computed tomography scan finding, bronchoscopic study was done and bronchial lavage was obtained. Bronchial lavage was positive for acid fast bacilli. Bronchoscopy showed fistula formation between the right and left main bronchus, a rare manifestation of EBTB. The patient was treated with antituberculosis therapy, and her symptoms improved and radiological findings showed regression of pulmonary lesions.