Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer.

BACKGROUND: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. PATIENTS AND METHODS: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. RESULTS: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. CONCLUSION: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.

Intradialytic hypotension: beyond hemodynamics.

Intradialytic hypotension is a major complication during hemodialysis session, associated with increased risk of cardiovascular events and mortality. Its pathophysiology is believed to be multifactorial and remains not well elucidated. The aim of this study is to put forward new mechanisms behind the development of intradialytic hypotension. The study included sixty-five subjects on chronic hemodialysis, divided into two groups: intradialytic hypotensive (n=12) and normotensive (n=53), according to the variation of systolic blood pressure between post-dialysis and pre-dialysis measurements. Renin and angiotensin converting enzyme I plasma concentrations increased in both groups but more likely in normotensive group. Aldosterone plasma concentration is increased in the normotensive group while it decreased in the intradialytic hypotension group. Plasma endothelin concentrations showed higher values in intradialytic hypotension group. Post-dialysis asymmetric dimethylarginine and angiotensin converting enzyme 2 plasma concentrations were significantly higher in intradialytic hypotension group as compared to normotensive one. Collectrin plasma concentrations were significantly lower in intradialytic hypotension group. Finally, post-dialysis vascular endothelial growth factor C plasma concentration significantly increased in intradialytic hypotension group. In conclusion, endothelial dysfunction characterized by a lower level of vasoactive molecule seems to play a critical role in intradialytic hypotension development.

Adolescents' self-perceived and actual weight: Which plays a dominant role in weight loss behaviour in Lebanon?

BACKGROUND: The decision to lose weight among adolescents is complex and is guided by a number of body-related factors. This study examined the extent of agreement between actual weight, measured as body mass index, and self-perceived weight and assessed their relative importance in weight loss behaviour among Lebanese adolescents. METHODS: Data on 278 adolescents aged 13-17 years were drawn from the nationwide Nutrition and Non-Communicable Disease Risk Factor Survey (Lebanon, 2009). Binary multivariable logistic regressions were conducted to test associations with "effort to lose weight" as the outcome variable, controlling for a number of potential confounders. RESULTS: Close to 36% reported trying to lose weight. Around 21% and 13% were overweight and obese, respectively, and 40% and 10% perceived their weight as slightly high and very high, respectively. Inaccurate perceivers, those underestimating or overestimating their weight, constituted 39%, with overall percent agreement between actual and self-perceived weight being 60.8% (kappa statistic = 0.319, 95% CI [0.242, 0.396]). About a third of the overweight adolescents (30.5%) and more than half of the obese (56.8%) underestimated their weight. In the multivariable analysis, self-perceived weight was statistically significant and a stronger predictor of weight loss effort than body mass index (adjusted odds ratios = 14.42 and 6.42 for slightly high and very high perceived weight, respectively, compared to odds ratios = 1.47 and 2.31 for overweight and obese adolescents, respectively). CONCLUSION: Health professionals need to consider self-perceived weight in conjunction with actual weight in their pursuit of weight management goals and in planning prevention programmes that guide weight loss behaviours for adolescents.

Cost-benefit analysis: newborn screening for inborn errors of metabolism in Lebanon.

OBJECTIVES: Few countries in the Middle East-North Africa region have adopted national newborn screening for inborn errors of metabolism by tandem mass spectrometry (MS/MS). We aimed to evaluate the cost-benefit of newborn screening for such disorders in Lebanon, as a model for other developing countries in the region. METHODS: Average costs of expected care for inborn errors of metabolism cases as a group, between ages 0 and 18, early and late diagnosed, were calculated from 2007 to 2013. The monetary value of early detection using MS/MS was compared with that of clinical "late detection", including cost of diagnosis and hospitalizations. RESULTS: During this period, 126000 newborns were screened. Incidence of detected cases was 1/1482, which can be explained by high consanguinity rates in Lebanon. A reduction by half of direct cost of care, reaching on average 31,631 USD per detected case was shown. This difference more than covers the expense of starting a newborn screening programme. CONCLUSION: Although this model does not take into consideration the indirect benefits of the better quality of life of those screened early, it can be argued that direct and indirect costs saved through early detection of these disorders are important enough to justify universal publicly-funded screening, especially in developing countries with high consanguinity rates, as shown through this data from Lebanon.

Barriers to the delivery of optimal antidiabetic therapy in the Middle East and Africa.

BACKGROUND: The prevalence of type 2 diabetes is increasing worldwide, but developing nations will bear a disproportionate share of this burden. Countries in the Middle East and Africa are in a state of transition, where marked disparities of income and access to education and healthcare exist, and where the relatively young populations are being exposed increasingly to processes of urbanisation and adverse changes in diet that are fuelling the diabetes epidemic. Optimising diabetes care in these nations is crucial, to minimise the future burden of complications of diabetes. METHODS: We have reviewed the barriers to effective diabetes care with special relevance to countries in this region. RESULTS: The effects of antidiabetic treatments themselves are unlikely to differ importantly in the region compared with elsewhere, but economic inequalities within countries restrict access to newer treatments, in particular. Values relating to family life and religion are important modifiers of the physician-patient interaction. Also, a lack of understanding of diabetes and its treatments by both physicians and patients requires more and better diabetes education, delivered by suitably qualified health educators. Finally, sub-optimal processes for delivery of care have contributed to a lack of proper provision of testing and follow-up of patients in many countries. CONCLUSION: Important barriers to the delivery of optimal diabetes care exist in the Middle East and Africa.

Barriers to the delivery of diabetes care in the Middle East and South Africa: a survey of 1,082 practising physicians in five countries.

AIMS: Developing countries face a high and growing burden of type 2 diabetes. We surveyed physicians in a diverse range of countries in the Middle East and Africa (Egypt, Kingdom of Saudi Arabia, United Arab Emirates, South Africa and Lebanon) with regard to their perceptions of barriers to type 2 diabetes care identified as potentially important in the literature and by the authors. METHODS: One thousand and eighty-two physicians completed a questionnaire developed by the authors. RESULTS: Most physicians enrolled in the study employed guideline-driven care; 80-100% of physicians prescribed metformin (with lifestyle intervention, where there are no contraindications) for newly diagnosed type 2 diabetes, with lifestyle intervention alone used where metformin was not prescribed. Sulfonylureas were prescribed widely, consistent with the poor economic status of many patients. About one quarter of physicians were not undertaking any form of continuing medical education, and relatively low proportions of practices had their own diabetes educators, dieticians or diabetic foot specialists. Physicians identified the deficiencies of their patients (unhealthy lifestyles, lack of education and poor diet) as the most important barriers to optimal diabetes care. Low-treatment compliance was not ranked highly. Access to physicians did not appear to be a problem, as most patients were seen multiple times per year. CONCLUSIONS: Physicians in the Middle East and South Africa identified limitations relating to their patients as the main barrier to delivering care for diabetes, without giving high priority to issues relating to processes of care delivery. Further study would be needed to ascertain whether these findings reflect an unduly physician-centred view of their practice. More effective provision of services relating to the prevention of complications and improved lifestyles may be needed.

Resistance to aspirin and clopidogrel therapy.

INTRODUCTION: Despite increasing evidence on the roles of aspirin and clopidogrel in decreasing morbidity and mortality from cardiovascular disease, resistance to therapy remains an emerging clinical entity. The aim of this review was to revisit current knowledge of the mechanisms, laboratory evaluation, clinical impact and management of resistance to aspirin and clopidogrel therapy. METHODS: Potentially relevant studies were identified from an electronic search of MEDLINE and PubMed databases. There were no language or publication year restrictions. References in published articles were also reviewed. RESULTS: Several definitions for resistance have been set, and various laboratory testing modalities are available. The pathophysiological mechanisms remain poorly understood; yet, several extrinsic, intrinsic and genetic factors are described. The clinical implications of this phenomenon are alarming and warrant concern. Management is currently limited to dosing alteration and introduction of other antiplatelet agents. CONCLUSION: Data from ongoing and future studies are awaited to better understand this entity and to highlight the most appropriate treatment strategies.

Optimising the medical management of hyperglycaemia in type 2 diabetes in the Middle East: pivotal role of metformin.

AIMS: Increases in the prevalence of type 2 diabetes will likely be greater in the Middle East and other developing countries than in most other regions during the coming two decades, placing a heavy burden on regional healthcare resources. METHODOLOGY: Medline search, examination of data from major epidemiological studies in the Middle Eastern countries. RESULTS: The aetiology and pathophysiology of diabetes appears comparable in Middle Eastern and other populations. Lifestyle intervention is key to the management of diabetes in all type 2 diabetes patients, who should be encouraged strongly to diet and exercise. The options for pharmacologic therapy in the management of diabetes have increased recently, particularly the number of potential antidiabetic combinations. Metformin appears to be used less frequently to initiate antidiabetic therapy in the Middle East than in other countries. Available clinical evidence, supported by current guidelines, strongly favours the initiation of antidiabetic therapy with metformin in Middle Eastern type 2 diabetes patients, where no contraindications exist. This is due to its equivalent or greater efficacy relative to other oral antidiabetic treatments, its proven tolerability and safety profiles, its weight neutrality, the lack of clinically significant hypoglycaemia, the demonstration of cardiovascular protection for metformin relative to diet in the UK Prospective Diabetes Study and in observational studies, and its low cost. Additional treatments should be added to metformin and lifestyle intervention as diabetes progresses, until patients are receiving an intensive insulin regimen with or without additional oral agents. CONCLUSIONS: The current evidence base strongly favours the initiation of antidiabetic therapy with metformin, where no contraindications exist. However, metformin may be under-prescribed in the Middle East.

[Gastro-intestinal tract tuberculosis: a little documented form of a too well-known infection]. / La tuberculose intestinale: une forme méconnue d'une infection trop connue.

In France, tuberculosis (TB) is still a health issue among underprivileged people and immigrants. We report a case of disseminated tuberculosis with intestinal involvement causing ill absorption and thus, making oral treatment impossible. Intestinal TB is often underrated and yet, malabsorption may lead to treatment failure or to developing antibiotic resistance. This type of tuberculosis must be systematically investigated when assessing the damage caused by tuberculosis and, more particularly, if there is any abdominal pain as well as clinical and biological signs of malabsorption. Parenteral antibiotherapy and nutrition must be systematically discussed.

The effect of delaying radiation therapy for systemic chemotherapy on local-regional control in breast cancer.

BACKGROUND: It remains controversial as to whether the administration of chemotherapy prior to radiation following the surgical treatment for localized breast cancer compromises local control. METHODS: The outcome of 290 patients who received chemotherapy prior to breast or chest wall irradiation following curative breast cancer surgery was retrospectively analyzed to determine if delaying radiation from the time of surgery adversely affects local-regional control. The patients were divided into three groups according to the time interval from definitive surgery to the start of radiation: group 1, < 5 months; group 2, 5 to < 7 months, and group 3, 7+ months. Local-regional and distant failure events were analyzed according to the time delay from surgery to radiation. RESULTS: The median follow-up was 6.0 years (range, 7 months to 15 years). Loco-regional failure was observed in 22 patients, 18 of which occurred within the original radiation fields. There was no significant adverse effect on local control or distant failure from delaying radiation for systemic chemotherapy. Univariate and multivariate analyses revealed that positive margins after surgery were associated with increased local recurrence. CONCLUSION: Delaying radiation therapy for greater than 7 months, in order to administer chemotherapy following curative breast cancer surgery, does not compromise local control. However, positive margins were significantly associated with higher rates of local failure and even an increase in radiation boost dose was not able to fully counteract the increased risk of local failure.

Heterosexual awareness and practices among Lebanese male conscripts.

To assess sexual behaviour and awareness about sexually transmitted infections (STIs) among young male adults in Lebanon, and to explore determinants associated with increasing levels of sexual risk, a cross-sectional survey of 730 conscripts was conducted. About 50% reported any lifetime heterosexual experience. Non-mutually exclusive sex predominated, and only half of the respondents reported consistent condom use during insertive vaginal sex. Higher sexual risk-taking was associated with urban residence, higher education, lower family crowding and younger age at first sexual experience. A national strategy with epidemiological and behavioural surveillance and educational programmes must be initiated before sexual risk-taking and incidence of STIs become a major public health issue.

Heterosexual awareness and practices among Lebanese male conscripts

To assess sexual behaviour and awareness about sexually transmitted infections [STIs] among young male adults in Lebanon, and to explore determinants associated with increasing levels of sexual risk, a cross-sectional survey of 730 conscripts was conducted. About 50% reported any lifetime heterosexual experience. Non-mutually exclusive sex predominated, and only half of the respondents reported consistent condom use during insertive vaginal sex. Higher sexual risk-taking was associated with urban residence, higher education, lower family crowding and younger age at first sexual experience. A national strategy with epidemiological and behavioural surveillance and educational programmes must be initiated before sexual risk-taking and incidence of STIs become a major public health issue

Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel.

BACKGROUND: Some chemotherapy (CT) drugs, including taxanes, may enhance the effectiveness of radiation therapy (RT). However, combining these therapies may increase the incidence of radiation pneumonitis, a lung inflammation. In a retrospective cohort study, we evaluated the incidence of radiation pneumonitis in breast cancer patients treated with RT and standard adjuvant CT by use of doxorubicin (Adriamycin) and cyclophosphamide, with and without paclitaxel. METHODS: Forty-one patients with breast cancer were treated with RT and adjuvant CT, including paclitaxel. Paclitaxel and RT (to breast-chest wall in all and lymph nodes in some) were delivered sequentially in 20 patients and concurrently in 21 patients. Paclitaxel was given weekly in some patients and every 3 weeks in other patients. The incidence of radiation pneumonitis was compared with that among patients in our database whose treatments did not include paclitaxel (n = 1286). The percentage of the lung volume irradiated was estimated. The Cox proportional hazards model was used to find covariates that may be associated with the observed outcomes. All P values were two-sided. RESULTS: Radiation pneumonitis developed in six of the 41 patients. Three patients received paclitaxel concurrently with RT, and three received it sequentially (P =.95). The mean percentage of lung volume irradiated was 20% in patients who developed radiation pneumonitis and 22% in those who did not (P =.6). For patients treated with CT including paclitaxel, the crude rate of developing radiation pneumonitis was 14.6% (95% confidence interval [CI] = 5.6% to 29.2%). For patients treated with CT without paclitaxel, the crude rate of pneumonitis was 1.1% (95% CI = 0.2% to 2.3%). The difference between the crude rates with or without paclitaxel is highly statistically significant (P<.0001). The mean time to develop radiation pneumonitis in patients treated concurrently with RT and paclitaxel was statistically significantly shorter in patients receiving paclitaxel weekly than in those receiving it every 3 weeks (P =.002). CONCLUSIONS: The use of paclitaxel and RT in the primary treatment of breast cancer should be undertaken with caution. Clinical trials with the use of combination CT, including paclitaxel plus RT, whether concurrent or sequential, must evaluate carefully the incidence of radiation pneumonitis.

The anti-thromboxane A2 synthetase activity of myocardial tissue and its variation during ischemia and reperfusion in isolated rabbit heart.

In this investigation, an anti-thromboxane A2 (TXA2) synthetase activity in the myocardial tissue, which can be modulated by ischemia and reperfusion, was observed. Regional ischemia was induced by 60 min occlusion of the left anterior descending coronary artery in isolated Langendorff rabbit hearts. Biosynthesis of TXA2 was carried out by using arachidonic acid (AA) as substrate, horse platelet microsomes (HPM) as the source of TXA2 synthetase and left ventricle microsomes (LVM) from ischemic and non-ischemic areas as effectors TXB2, the stable metabolite of TXA2, was determined by radioimmunoassay. Experiments carried out under the adopted conditions showed that LVM from control hearts were able to inhibit by up to 50% the biosynthesis of TXA2 from HPM. This anti-TXA2 synthetase activity was more pronounced when LVM from the non-ischemic area were used, rather then LVM from the ischemic one. A 60 min reperfusion decreased the anti-TXA2 activity. A superfused rabbit aorta strip was also used as a cascade bioassay to study the effect of LVM on the TX2-synthetase activity of HPM, and this confirmed our findings. These results suggest that the left ventricle possesses a self-defense mechanism against acute myocardial ischemia, independently from the circulation. The postulated mechanism may be initiated in the non-ischemic area.

Ultrasonographic and Doppler study of the thyroid gland in Graves' disease before and after treatment with antithyroid drugs.

OBJECTIVE: To determine the effects of medical treatment on the thyroid gland, peripheral circulation, and laboratory findings in patients with Graves' disease. METHODS: Twenty patients with Graves' disease were treated with either carbimazole and propranolol (group I) or carbimazole only (group II). Serum free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and thyrotropin-binding inhibitory immunoglobulins (TBII) were estimated before and after 6 weeks of treatment. Duplex Doppler ultrasonographic examination of the thyroid, inferior thyroid artery (ITA), and common carotid artery (CCA) was performed before and after 2, 4, and 6 weeks of therapy. RESULTS: Serum FT(4) and TBII decreased after treatment in both groups, whereas serum TSH increased in group I only. The volume of the thyroid gland and parenchymal blood velocity were increased in these patients and diminished only with addition of propranolol to carbimazole. A diffuse hypoechogenic pattern in the thyroid gland and increased ITA blood flow and peak velocity were observed in all patients and persisted throughout treatment. The mean CCA peak blood velocity was accelerated in Graves' disease and diminished after 6 weeks of therapy in both groups, whereas increased CCA blood flow diminished only in group I. CONCLUSION: A 6-week period of therapy with carbimazole and propranolol has no effect on the diffuse low echogenic pattern in the thyroid gland and the accelerated ITA blood flow in Graves' disease. The addition of propranolol is associated with early decrements in thyroid volume, parenchymal vascularity, and CCA blood flow as well as early recovery of TSH suppression, but it has no additional effect on thyroid hormone secretion or TBII levels.

Risk factors for non-melanomatous skin cancer in Alexandria, Egypt.

The role of constitutional and environmental factors on the risk of non-melanomatous skin cancer was evaluated in a case-control study conducted in 1992 in Alexandria, Egypt, on 136 incident histologically confirmed (99 basal-cell and 37 squamous-cell) cases of non-melanomatous skin cancer (NMSC) and 145 controls in hospital for a broad spectrum of acute non-sun-related dermatological conditions. In relation to skin colour, compared with brown-skinned subjects, the multivariate relative risks (RR) were 2.3 for olive-skinned subjects and 3.8 for fair/medium-skinned subjects. Three cases and 29 controls were black (RR = 0.2). The trend in risk with skin colour was significant. Likewise, compared with subjects with brown or hazel eyes, those with green or blue eyes had a RR of 3.1. In relation to acute sun reaction, compared with subjects reporting easy tanning, the RRs were 2.5 for subjects reporting moderate tanning and 4.7 for those reporting easy burning. The risk of NMSC was higher for subjects reporting an outdoor occupation than for those reporting an indoor occupation (RR = 7.7). A significant trend in risk was observed with degree of sun exposure: compared with subjects reporting light sun exposure, the RR was 3.0 for those reporting moderate exposure, and 6.1 for those reporting heavy sun exposure. There was an indication of a relationship between clothing pattern and skin-cancer risk: compared with subjects reporting frequent use of traditional Egyptian clothes, the RR for dressing in short clothes was 1.8. The presence of signs of photodamage was also associated with NMSC (RR = 3.7). Exposure to arsenic was reported by 10 cases and 1 control (RR = 9.5). A positive interaction between sun exposure and skin colour was observed, and the RR rose to 14.2 for medium- or fair-skinned subjects with heavy exposure compared with brown- or black-skinned subjects with light or moderate sun exposure. In this Egyptian population, over 60% of NMSC could be attributed to sun exposure and approximately 45% to skin colour.