[Inhaled marijuana and the lung, a toxic cocktail?] / Cannabis inhalé et poumon, une liaison dangereuse ?

Unlike the well-documented effects of tobacco smoke on the lung, the effects of cannabis smoke remain controversial, the main bias consisting in co-consumption of tobacco. That said, the composition of joint smoke is close to that of cigarettes, containing many compounds that are carcinogenic and/or alter the respiratory epithelium. Confirmed respiratory effects in chronic cannabis smokers include aggravated chronic bronchitis symptoms, a cumulative effect with tobacco on COPD and emphysema occurrence, an increased risk of bullous emphysema, and pneumothorax with heightened risk of recurrence after pleural symphysis. Recent prospective studies have shown a negative impact on lung function, with not only damage to the airways, but also DLCO alteration and an accelerated drop in FEV1. Finally, cannabis smoking is very common among young patients with lung cancer. Its consumption could lead to a different lung cancer profile, potentially more undifferentiated and less accessible to targeted therapy. Questioning about cannabis consumption must be systematic and targeted medical care should be offered.

Transdermal nicotine in non-smokers: A systematic review to design COVID-19 clinical trials.

Recent data show an interaction between COVID-19 and nicotine and indicate the need for an assessment of transdermal nicotine use in non-smokers. Assessments have been conducted into the short-term cognitive effects of nicotine and into diseases such as Parkinson's, Tourette syndrome, ADHD or ulcerative colitis. METHODS: Analyses of nicotine administration protocols and safety were conducted after reviewing Medline and Science Direct databases performing a search using the words [transdermal nicotine] AND [non-smoker] AND selected diseases. RESULTS: Among 298 articles identified, there were 35 reviewed publications reporting on 33 studies of non-smokers receiving transdermal nicotine for >48hours. In the 16 randomized trials, 7 crossover, 1 case/control and 9 open studies patients received an initial nicotine dose of between 2.5mg and 15mg/day. In 22 studies, daily doses increased by 2 to 7 steps in 3 to 96 days until the dose was between 5mg and 105mg/day. The target nicotine dose was 19.06±20.89mg/day. The 987 non-smokers (534 never-smokers, 326 ex-smokers and 127 classified as "non-smokers") received or did not receive nicotine. The most common side-effects were nausea and skin itching. Forty-three (7.1%) non-smokers stopped treatment because of an adverse event of nicotine. No hospitalization related to nicotine side-effects were reported. CONCLUSION: Despite a relatively safe tolerance profile, transdermal nicotine therapy in non-smokers can only be used in clinical trials. There is a lack of formal assessment of the potential risk of developing a tobacco addiction. This review offers baseline data to set a transdermal nicotine protocol for non-smokers with a new purpose.

Practical guidelines on e-cigarettes for practitioners and others health professionals. A French 2016 expert's statement.

A group of 11 French medical experts has developed guidelines through a Delphi progressive consensus about smoking management at the e-cigarette era. The lack of scientific data about e-cigarettes led the experts to set out recommendations, mainly based on clinical practice while waiting for scientific validations. The validated smoking cessation treatments keep the first place in the prevention and the treatment of tobacco-induced damages. The e-cigarette, experimented by a large proportion of smokers, is a safer product than tobacco. The health professional must answer the patients about the e-cigarettes: (1) A smoker who questions about e-cigarettes should receive information. Even if there is a lack of data, e-cigarettes offer much lower risks than tobacco. (2) A dual user is at high risk of returning to exclusive tobacco use; he should also optimize other nicotine intakes by combining nicotine replacement therapy and/or optimizing the nicotine intake through the e-cigarette. (3) A smoker who wish to use the e-cigarette in order to quit with or without associated pharmacological treatment should be accompanied and not discouraged. (4) A vaper who is tired to continuing to vape should be accompanied to quit. Specific guidelines are also provided for adolescents, pregnant women, patients during perioperative periods and also for pulmonary, cardiac and schizophrenic patients.

'Carriers of variant luteinizing hormone (V-LH) among 1593 Baltic men have significantly higher serum LH'.

Luteinizing hormone (LH) is a pituitary heterodimeric glycoprotein essential in male and female reproduction. Its functional polymorphic variant (V-LH) is determined by two missense mutations (rs1800447, A/G, Trp8Arg; rs34349826, A/G, Ile15Thr) in the LH ß-subunit encoding gene (LHB; 19q13.3; 1111 bp; 3 exons). Among women, V-LH has been associated with higher circulating LH and reduced fertility, but the knowledge of its effect on male reproductive parameters has been inconclusive. The objective of this study was to assess the effect of V-LH on hormonal, seminal and testicular parameters in the Baltic young men cohort (n = 986; age: 20.1 ± 2.1 years) and Estonian idiopathic infertility patients (n = 607; 35.1 ± 5.9 years). V-LH was detected by genotyping of the underlying DNA polymorphisms using PCR-RFLP combined with resequencing of a random subset of subjects. Genetic associations were tested using linear regression under additive model and results were combined in meta-analysis. No significant difference was detected between young men and infertility patients for the V-LH allele frequency (11.0 vs. 9.3%, respectively). V-LH was associated with higher serum LH in both, the young men cohort (p = 0.022, allelic effect = 0.26 IU/L) and the idiopathic infertility group (p = 0.008, effect = 0.59 IU/L). In meta-analysis, the statistical significance was enhanced (p = 0.0007, resistant to Bonferroni correction for multiple testing; effect = 0.33 IU/L). The detected significant association of V-LH with increased serum LH remained unchanged after additional adjustment for the SNPs previously demonstrated to affect LH levels (FSHB -211G/T, FSHR Asn680Ser, FSHR -29A/G). Additionally, a suggestive trend for association with reduced testicular volume was observed among young men, and with lower serum FSH among infertility patients. The V-LH carrier status did not affect sperm parameters and other circulating reproductive hormones. For the first time, we show a conclusive contribution of V-LH to the natural variance in male serum LH levels. Its downstream clinical consequences are still to be learned.

[Biocompatibility of composites--literature review].

Composites are a large family of materials composed of polymer matrices imbedded with different types of fillers. The specific properties achievable with diverse chemical combinations provide for a wide range of implications in many industrial fields. Materials designed for medical use must not only efficiently serve the purpose of their use, but also be biocompatible to the tissues they contact and the body as a whole. Dental composites and their components have been studied intensely to assess their potential local and systemic side effects, to establish biocompatibility, in order to receive the proper conformation allowing their safe clinical use. The purpose of the following paper is to summarize several aspects of research focused on determining cytotoxicity, genotoxicity, carcinogenicity, hypersensitivity, and microbial effects of composite components, in order to ascertain in fact how biocompatible dental composite materials are. Research shows that several chemical components may be released from different types of composites, and are able to cause toxic, allergic, mutagenic and other biological effects. However, because of the small amounts applied and the unique conditions in the oral cavity, the clinical relevance of these findings is questionable. Nevertheless, caution should be taken when using these materials, to avoid possible negative outcomes. Future studies should focus on targeting most toxic components and finding biocompatible alternatives and development of materials with high polymerization efficiency in order to reduce the amount of leachable components.

Health impact in children and adolescents.

Obesity in children and adolescents is associated with multiple comorbidities, including metabolic, cardiovascular, gastrointestinal, pulmonary, orthopedic and psychological disorders. In fact, cardiovascular and metabolic impairments in childhood and adolescence constitute major risk factors for developing cardiovascular disease in adulthood. Thus, obesity in childhood and adolescence leads to a higher morbidity and mortality in adulthood. Therefore, strong emphasis must be laid on the prevention and therapy of childhood obesity. Treatment requires a multidisciplinary and multiphase approach including dietary management, physical activity, pharmacotherapy and bariatric surgery. This paper reviews the different comorbidities of childhood obesity supporting the notion of a multidisciplinary therapy concept.

Follicular fluid protein content (FSH, LH, PG4, E2 and AMH) and polar body aneuploidy.

PURPOSE: Our objective was to identify a marker for oocyte aneuploidy in follicular fluid (FF) in women with an increased risk of oocyte aneuploidy after controlled ovarian hyperstimulation. MATERIALS AND METHODS: Three groups of oocytes were constituted for polar body screening by FISH (chromosomes 13, 16, 18, 21 and 22): Group 1, advanced maternal age (n = 156); Group 2, implantation failure (i.e. no pregnancy after the transfer of more than 10 embryos; n = 101) and Group 3, implantation failure and advanced maternal age (n = 56). FSH and other proteins were assayed in the corresponding FF samples. RESULTS: Of the 313 oocytes assessed, 35.78 % were abnormal. We found a significant difference between the follicular FSH levels in normal oocytes and abnormal oocytes (4.85 ± 1.75 IU/L vs. 5.41 ± 2.47 IU/L, respectively; p = 0.021). We found that the greater the number of chromosomal abnormalities per oocyte (between 0 and 3), the higher the follicular FSH level. CONCLUSION: High FF FSH levels were associated with oocyte aneuploidy in women having undergone controlled ovarian hyperstimulation.

Strong correlation between liver and serum levels of hepatitis C virus core antigen and RNA in chronically infected patients.

HCV core antigen (Ag) and HCV RNA levels were evaluated in matched liver biopsy samples and sera from 22 patients with hepatitis C infection by using the quantitative Architect HCV Ag immunoassay and a real-time RT-qPCR assay, respectively. The data showed a strong correlation between liver and serum compartments of HCV Ag levels (r = 0.80) and HCV RNA levels (r = 0.87). In summary, the serum HCV Ag and RNA levels reflect the intrahepatic values.

High prevalence of advanced fibrosis in association with the metabolic syndrome in a Belgian prospective cohort of NAFLD patients with elevated ALT. Results of the Belgian NAFLD registry.

INTRODUCTION: Non-alcoholic Fatty Liver Disease (NAFLD) is increasingly recognised as a source of liver related morbidity and mortality. Hard data on epidemiology and natural history are scarce. AIM: To study demographic and metabolic characteristics of the NAFLD patients seen by Belgian hepatologists. METHODS: Belgian hepatologists filled in a questionnaire for every newly diagnosed NAFLD patient between January 1st and December 31st 2004. Liver biopsy was advised if ALT > 1.5 x ULN and if 3/5 of the criteria for the metabolic syndrome (MS) (ATPI-II) were present, but was not mandatory. Biopsy was scored using the Brunt classification. RESULTS: 230 patients were prospectively included in 9 centres; 54% were males; mean age was 49.4 +/- 13.9 y; mean BMI was 30.6 +/- 4.6 kg/m2. The MS was present in 53%. In 16% formerly undiagnosed diabetes was discovered. 51% had a liver biopsy: 25% met the criteria, 26% did not. Grading did not differ between patients with or without MS. Staging was significantly more severe in patients with MS (2.43 +/- 1.25 vs. 1.73 +/- 1.18, p < 0.001). A subgroup of patients with GGT > 5 x ULN were significantly older (55.9 vs. 47.64 y, p = 0.02), more frequently diabetic (53% vs. 23%, p = 0.01) and had more advanced fibrosis (3.42 vs. 1.08, p = 0.008). ALT levels were variable. CONCLUSIONS: The MS is highly prevalent in Belgian NAFLD patients and is associated with more severe disease. Mild to moderate fibrosis is frequent, and the proposed criteria for liver biopsy are not accurate in selecting these patients. Patients with elevated GGT constitute a subgroup with more advanced disease.

A European evidence-based guideline for the prevention of type 2 diabetes.

BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.

Assessment of candidate biomarkers of drug-induced hepatobiliary injury in preclinical toxicity studies.

This study was designed to assess the value of a set of potential markers for improved detection of liver injury in preclinical toxicity studies. Male Wistar rats were treated with drug candidates (BAY16, EMD335823, BI-3) that previously failed during development, in part due to hepatotoxicity, at two dose levels for 1, 3 and 14 days. Concentrations of lipocalin-2/NGAL and clusterin, which are frequently overexpressed and released from damaged tissues, and thiostatin, recently identified within PredTox as being elevated in urine in response to liver injury, were determined in rat urine and serum by ELISA. This was supplemented by confirmatory qRT-PCR and immunohistochemical analyses in the target organ. Serum paraoxonase-1 activity (PON1), which has been suggested as a marker of hepatotoxicity, was determined using a fluorometric assay. Clusterin and PON1 were not consistently altered in response to liver injury. In contrast, thiostatin and NGAL were increased in serum and urine of treated animals in a time- and dose-dependent manner. These changes correlated well with mRNA expression in the target organ and generally reflected the onset and degree of drug-induced liver injury. Receiver-operating characteristics (ROC) analyses supported serum thiostatin, but not NGAL, as a better indicator of drug-induced hepatobiliary injury than conventional clinical chemistry parameters, i.e. ALP, ALT and AST. Although thiostatin, an acute phase protein expressed in a range of tissues, may not be specific for liver injury, our results indicate that thiostatin may serve as a sensitive, minimally-invasive diagnostic marker of inflammation and tissue damage in preclinical safety assessment.

[Organized colorectal screening in French Community of Belgium and polyp surveillance]. / Le dépistage organisé du cancer colorectal en Communauté française de Belgique et surveillance des polypes.

Colorectal cancer is an important health care problem in Belgium and screening is now widely recommendend. The French Community has launched in March 2009, a campaign to build public and professional awareness of the importance of screening for colorectal cancer. With the goal of encouraging all persons age 50 to 74 to actively gain information and seek screening with the active participation of their house doctors, the campaign will work to clarify any myths or fears about screening options and ensure that the importance of screening and early detection will be understood. The program in the French Community propose guaiac-based fecal occult blood testing for average risk people and, in case of positivity a colonoscopy must be performed. A high quality colonoscopy should be offered first in case of significant personal and familial history of adenomas, colorectal cancer and some specific extracolonic neoplasia. Several strategies will be used to ensure follow up of this program and encourage wide participation of the population.

[Colorectal cancer screening: an absolute necessity and an imminent reality in the French community]. / Le dépistage généralisé du cancer colorectal: une absolue nécessité et une réalité imminente en Communauté française.

Colorectal cancer is a true problematic of public health. The screening is an absolute necessity. An ambitious program of screening is launched in French Community. Faecal occult blood test (FOBT) will be proposed to average risk patients in general population. A total colonoscopy will be performed if FOBT will be positive. First step colonoscopy will be proposed to high or very high risk patients. General practitioners are in the core of the multidisciplinary program.

A pilot observational survey of hepatitis C in Belgium.

AIM OF THE STUDY: There is a lack of epidemiological data on hepatitis C (HCV) infected patients in Belgium. Therefore our purpose was to address this important question and to evaluate the feasibility of a national HCV observatory. PATIENTS AND METHODS: From November 2003 to November 2004, every new patient prospectively seen for HCV antibody positivity in 9 Belgian hospital centres was recorded and a standardised 10-items questionnaire was completed during the consultation, including a Quality of Live (QOL) visual analogue scale. RESULTS: Three hundred and eighteen consecutive patients were recruited. Fifty five percent were male with a median age of 45 y (11-87 y). The main risk factors for infection were IV drug use (27%), blood transfusion (23%), and invasive medical procedure (11%). On the QOL scale, ranging from 0 and 100, mean value was 61 +/- 31. Transaminases were abnormal in 66% with a median elevation 2 times above normal value. HCV RNA was positive in 87% with a viral load above 800 000 IU/ml in 42%. Genotype 1 was predominant (59%), followed by genotypes 3 (19%) and 4 (14%). A liver biopsy was performed in 190 patients, with minimal fibrosis (METAVIR F0-F1) in 43%, moderate fibrosis (F2) in 35% and advanced stages (F3-F4) in 22%. Antiviral treatment was not considered in 53% because of normal ALT (30%), old age (7%), minimal histological stage (6%) or patient refusal (4%). CONCLUSIONS: This study highlights the feasibility of a national HCV survey using a simple questionnaire. This pilot study could be generalised throughout Belgium, and, if repeated, could allow a regular assessment of the changes in epidemiology and management of HCV infection in our country.

[How to prevent complications of liver cirrhosis?]. / Comment prévenir les complications de la cirrhose?

Liver cirrhosis is the end-stage of chronic liver disease. Even at the compensated stage complications are multiple, severe and potentially fatal which are related to liver insufficiency, portal hypertension and a pre-cancerous stage. It is now possible to diagnose cirrhosis through non invasive tools like biochemical scores and Fibroscan. It may be reversible provided adequate counselling about excessive alcohol intake and metabolic syndrome and specific treatments such as antivirals, venesection, immunosuppressive therapies are implemented. The role of the general practitioner is to diagnosis and treat cirrhosis early together with the hepatogastroenterologist. He can also, through simple means, prevent complications such as hepatocellular carcinoma, variceal bleeding, overt encephalopathy and renal failure and liver decompensation after surgery.

A primary peritoneal pseudomyxoma peritonei arising from the Mullerian tissue: a case report.

A primary Pseudomyxoma Peritonei is uncommon. For a long time, ovaries, colon and appendix were proposed like a site origin of these enigmatic lesions. Recent publications show that the majority of cases are due to a rupture of appendicle adenoma. We report a case of a pseudomyxoma peritonei arising in an elderly patient with a previous medical history of appendectomy undergone in infancy. The pseudomyxoma was misdiagnosed as an abdominal abscess related to colitis. In our opinion, metaplasia of the Müllerian system is a possible source of a primary peritoneal pseudomyxoma.

The management of patients with mild hepatitis C.

Infection with the hepatitis C virus (HCV) represents an important public health problem and is a leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is a heterogeneous disease. Many patients have mild disease at presentation but not all of them will develop advanced liver disease. However, the identification of these patients with mild hepatitis C who will show progressive disease is difficult and is based on histological criteria and the assessment of co-factors (age, alcohol intake, steatosis). In addition, serum transaminases that are persistently normal on several occasions during 18 months may point to a more benign course. Patients with mild hepatitis C should not be excluded "a priori" from the possibility of being treated, as treatment with pegylated interferon and ribavirin is safe and effective in this group. Overall, the decision to initiate therapy should be individualized and based on the severity of the disease by liver biopsy, the potential of serious side effects, the probability of response and the motivation of the patient.