Fatigue visual analogue scale score correlates with quality of life in cancer patients receiving epoetin alfa (Sandoz) for chemotherapy-induced anaemia: The CIROCO study.

PURPOSE: Available tools to measure fatigue and health-related quality of life (HRQoL) in cancer patients are often difficult to use in clinical practice. The fatigue visual analogue scale (VAS) provides a simple method to assess fatigue. This study evaluated the correlation between HRQoL and fatigue perceived by cancer patients undergoing chemotherapy. METHODS: This was a non-interventional prospective study of adult cancer patients in France presenting with chemotherapy-induced anaemia (CIA) treated with epoetin alfa (Sandoz). Data were collected using an electronic case report form at study inclusion (T0), after 2-3 chemotherapy cycles (T1) and after 4-6 cycles (T2). RESULTS: The study included 982 patients from September 2015 to October 2017. Overall, there was a negative correlation between fatigue VAS and HRQoL. The overall haemoglobin (Hb) change between T0 and T2 was +17.8 % (± 18.1 %). Fatigue assessed by both patients and physicians showed a clinically significant improvement during the study. Global HRQoL also increased. CONCLUSION: Treatment of CIA with epoetin alfa (Sandoz) improved Hb levels, fatigue, and HRQoL, with a correlation observed between fatigue VAS score and HRQoL. Fatigue VAS could act as a simple alternative to more complex methods to measure HRQoL; however, further analyses are required to confirm this association.

Use of sugar in coffee and tea and long-term risk of mortality in older adult Danish men: 32 years of follow-up from a prospective cohort study.

BACKGROUND: Tea and coffee are the most consumed beverages worldwide and very often sweetened with sugar. However, the association between the use of sugar in tea or coffee and adverse events is currently unclear. OBJECTIVES: To investigate the association between the addition of sugar to coffee or tea, and the risk of all-cause mortality, cardiovascular mortality, cancer mortality and incident diabetes mellitus. METHODS: Participants from the prospective Copenhagen Male Study, included from 1985 to 1986, without cardiovascular disease, cancer or diabetes mellitus at inclusion, who reported regular coffee or tea consumption were included. Self-reported number of cups of coffee and tea and use of sugar were derived from the study questionnaires. Quantity of sugar use was not reported. Primary outcome was all-cause mortality and secondary endpoints were cardiovascular mortality, cancer mortality and incident diabetes mellitus, all assessed through the Danish national registries. The association between adding sugar and all-cause mortality was analyzed by Cox regression analysis. Age, smoking status, daily alcohol intake, systolic blood pressure, body mass index, number of cups of coffee and/or tea consumed per day and socioeconomic status were included as covariates. Vital status of patients up and until 22.03.2017 was assessed. Sugar could be added to either coffee, tea or both. RESULTS: In total, 2923 men (mean age at inclusion: 63±5 years) were included, of which 1007 (34.5%) added sugar. In 32 years of follow-up, 2581 participants (88.3%) died, 1677 in the non-sugar group (87.5%) versus 904 in the sugar group (89.9%). Hazard ratio of the sugar group compared to the non-sugar group was 1.06 (95% CI 0.98;1.16) for all-cause mortality. An interaction term between number of cups of coffee and/or tea per day and adding sugar was 0.99 (0.96;1.01). A subgroup analysis of coffee-only drinkers showed a hazard ratio of 1.11 (0.99;1.26). The interaction term was 0.98 (0.94;1.02). Hazard ratios for the sugar group compared to the non-sugar group were 1.11 (95% CI 0.97;1.26) for cardiovascular disease mortality, 1.01 (95% CI 0.87;1.17) for cancer mortality and 1.04 (95% CI 0.79;1.36) for incident diabetes mellitus. CONCLUSION: In the present population of Danish men, use of sugar in tea and/or coffee was not significantly associated with increased risk of mortality or incident diabetes.

Tetracycline antibiotics: Potential anticancer drugs.

In recent years, research on tetracycline antibiotics has gradually shifted from their antibacterial effects to anticancer effects. Doxycycline, minocycline, and tigecycline as the US Food and Drug Administration (FDA) approved tetracycline antibiotics have been the main subjects of studies. Evidence indicated that they have anticancer properties and are able to control cancer progression through different mechanisms, such as anti-proliferation, anti-metastasis, and promotion of autophagy or apoptosis. In addition, studies have shown that these three tetracycline antibiotics can be utilized in conjunction with chemotherapeutic and targeted drugs to inhibit cancer progression and improve the quality of patient survival. Therefore, doxycycline, minocycline, and tigecycline are taken as examples in this work. Their mechanisms of action in different cancers and related combination therapies are introduced. Their current roles in alleviating the suffering of patients undergoing chemotherapy when used as adjuvant drugs in clinical treatment are also described. Finally, the research gaps and potential research directions at this stage are briefly summarized.

What Is the Role of Nutraceutical Products in Cancer Patients? A Systematic Review of Randomized Clinical Trials.

Chemotherapy represents the main pharmacological cancer treatment. Recently, positive effects emerged with the combination of anticancer therapy and nutraceutical products. The aim of this systematic review is to collect and synthesize the available scientific evidence regarding the potential effects of nutraceuticals on cancer cells. A systematic literature search of randomized clinical trials of nutraceutical products in patients with cancer published up to 15 December 2022 was conducted using three data sources: Embase, PubMed, and Web of Science. The effect of high-dose isoflavone supplements on prostate cancer resulted in stabilization or reduction of PSA concentrations in 50% of isoflavone group patients six months after treatment. High doses of vitamin D supplementation plus chemotherapy in patients with advanced or metastatic colorectal cancer showed a median PFS of 13.0 months (95% CI, 10.1-14.7 months) for 49 patients. The effect of vitamin D supplementation on markers of inflammatory level and antioxidant capacity in women with breast cancer showed a significant increase in serum vitamin D concentration (28 ± 2.6 to 39 ± 3.5; p = 0.004) after 8 weeks of treatment. In conclusion, nutraceutical supplements represent a potentially growing sector and can be utilized in medical treatment or nutrition to provide integrated medical care.

High-dose folic acid and cancer risk; unjustified concerns by von Wrede and colleagues regarding our paper.

Women using antiseizure medication in pregnancy are often advised to use high doses of folic acid supplements (1mg to 5 mg) to reduce the risk of teratogenicity. Recently, we published a report showing an association between maternal prescription fill of high dose folic acid in relation to pregnancy and childhood cancer in the offspring. The report has sparked a debate about which dose of folic acid that should be recommended in pregnancy in women in need of antiseizure medication. In this Commentary, we explain our findings and the method used in our report, and answer recent questions that have emerged.

Long-term exposure to airborne metals and risk of cancer in the French cohort Gazel.

BACKGROUND: The specific compounds that make ambient fine particulate matter (PM2.5) carcinogen remain poorly identified. Some metals contribute to ambient PM2.5 and possibly to its adverse effects. But the challenge of assessing exposure to airborne metals limits epidemiological studies. OBJECTIVE: To analyze the relationships between several airborne metals and risk of cancer in a large population. METHODS: We estimated the individual exposure to 12 airborne metals of âˆ¼ 12,000 semi-urban and rural participants of the French population-based Gazel cohort using moss biomonitoring data from a 20-year national program. We used principal component analyses (PCA) to derive groups of metals, and focused on six single carcinogenic or toxic metals (arsenic, cadmium, chromium, lead, nickel, and vanadium). We used extended Cox models with attained age as time-scale and time-varying weighted average exposures, adjusted for individual and area-level covariables, to analyze the association between each exposure and all-site combined, bladder, lung, breast, and prostate cancer incidence. RESULTS: We identified 2,401 cases of all-site cancer between 2001 and 2015. Over the follow-up, median exposures varied from 0.22 (interquartile range (IQR): 0.18-0.28) to 8.68 (IQR: 6.62-11.79) µg.g-1 of dried moss for cadmium and lead, respectively. The PCA yielded three groups identified as "anthropogenic", "crustal", and "marine". Models yielded positive associations between most single and groups of metal and all-site cancer, with e.g. hazard ratios of 1.08 (95% CI: 1.03, 1.13) for cadmium or 1.06 (95% CI: 1.02,1.10) for lead, per interquartile range increase. These findings were consistent across supplementary analyses, albeit attenuated when accounting for total PM2.5. Regarding specific site cancers, we estimated positive associations mostly for bladder, and generally with large confidence intervals. CONCLUSION: Most single and groups of airborne metals, except vanadium, were associated with risk of cancer. These findings may help identify sources or components of PM2.5 that may be involved in its carcinogenicity.

Anti-inflammatory effect of combining fish oil and evening primrose oil supplementation on breast cancer patients undergoing chemotherapy: a randomized placebo-controlled trial.

Breast cancer is the most common malignant tumor and one of the leading causes of cancer-related death in women throughout the world. This study is a parallel, randomized, double-blind, controlled, 12-week supplementation trial, investigating the anti-inflammatory effects of dietary intake of fish oil and evening primrose oil (EPO), in patients with breast cancer undergoing chemotherapy. The primary outcomes were changes in the nutritional status and inflammatory cytokines of patients during the study. The secondary outcomes were changes in hematological and biochemical parameters and fatty acid profile. Of the 32 eligible patients, half of them is randomly assigned to a treatment arm with fish oil and EPO (n = 16), or a control arm (n = 16) with mineral oil as a placebo. The intervention group was taking 2 gel capsules of fish oil and 3 gel capsules of EPO (400 mg eicosapentaenoic acid, 600 mg docosahexaenoic acid, and 351 mg gamma-linolenic acid) fish oil and evening primrose oil for 12 weeks, during their chemotherapy. The control/placebo group was taking 5 gel capsules of 1g of mineral oil. One of the patients dropped out due to discontinuation of the treatment (in the placebo group) and two did not show up at the post-treatment measurements (in the intervention group), thus, 29 women completed the study. The results showed an increase in plasma levels of docosapentaenoic acid (22:5n-3), docosahexaenoic acid (22:6n-3), total n-3PUFA, vaccenic acid (18:1n-7), and a decrease in n-6/n-3 PUFA ratio in the intervention group. An increase in the plasma level of dihomo-gamma-linolenic acid (20:3n-6) was observed in the placebo group. There was no difference in plasma levels of interleukin (IL) IL-8, IL-10, and tumor necrosis factor-alpha, while the level of IL-6 decreased in both groups and was significantly lower in the intervention group at the end of the study. In conclusion, this supplementation improved the PUFA status and decreased the level of IL-6 in breast cancer patients undergoing chemotherapy. Consequently, this treatment may help reduce cancer complications resulting from impaired lipid metabolism and inflammation. ClinicalTrials.gov Identifier: NCT03516253. Date of registration 04/05/2018.

Evidence-Based Treatment of Pain in Chemotherapy-Induced Peripheral Neuropathy.

PURPOSE OF REVIEW: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and often painful condition that occurs after administration of chemotherapeutic agents. The primary objective of this systematic review was to appraise the literature on conservative, pharmacological, and interventional treatment options for CIPN pain. RECENT FINDINGS: There is level I evidence supporting modest to moderate improvement in CIPN pain from duloxetine treatment, as well as short-term modest improvement from physical therapy and acupuncture. Although opioid and cannabis administration may provide short-term modest improvement, administration is commonly limited by side effects. Generally, most studies reported no clinical benefit from yoga, topical neuropathic agents, gabapentinoids, and tricyclic antidepressants. Evidence is currently equivocal for scrambler therapy and transcutaneous electrical nerve stimulation. Finally, evidence on neuromodulation options is limited to mostly case reports/series and one observational study highlighting moderate improvement with auricular nerve stimulation. This systematic review provides an overview of conservative, pharmacologic, and interventional treatment modalities for CIPN pain. Furthermore, it provides a level of evidence and degree of recommendation based on the United States Preventive Services Task Force (USPSTF) criteria for each specific treatment modality.

Dietary intake of household cadmium-contaminated rice caused genome-wide DNA methylation changes on gene/hubs related to metabolic disorders and cancers.

Cadmium (Cd) contamination in food has raised broad concerns in food safety and human health. The toxicity of Cd to animals/humans have been widely reported, yet little is known about the health risk of dietary Cd intake at the epigenetic level. Here, we investigated the effect of a household Cd-contaminated rice (Cd-rice) on genome-wide DNA methylation (DNAm) changes in the model mouse. Feeding Cd-rice increased kidney Cd and urinary Cd concentrations compared with the Control rice (low-Cd rice), whereas supplementation of ethylenediamine tetraacetic acid iron sodium salt (NaFeEDTA) in the diet significantly increased urinary Cd and consequently decreased kidney Cd concentrations. Genome-wide DNAm sequencing revealed that dietary Cd-rice exposure caused the differentially methylated sites (DMSs), which were mainly located in the promoter (32.5%), downstream (32.5%), and intron (26.1%) regions of genes. Notably, Cd-rice exposure induced hypermethylation at the promoter sites of genes Caspase-8 and interleukin-1ß (Il-1ß), and consequently, their expressions were down-regulated. The two genes are critical in apoptosis and inflammation, respectively. In contrast, Cd-rice induced hypomethylation of the gene midline 1 (Mid1), which is vital to neurodevelopment. Furthermore, 'pathways in cancer' was significantly enriched as the leading canonical pathway. Supplementation of NaFeEDTA partly alleviated the toxic symptoms and DNAm alternations induced by Cd-rice exposure. These results highlight the broad effects of elevated dietary Cd intake on the level of DNAm, providing epigenetic evidence on the specific endpoints of health risks induced by Cd-rice exposure.

Safety of Combined Targeted and Helixor®Viscum album L. Therapy in Breast and Gynecological Cancer Patients, a Real-World Data Study.

BACKGROUND: Newer personalized medicines including targeted therapies such as PARP inhibitors and CDK 4/6 inhibitors have been shown to improve the survival of breast and gynaecological cancer patients. However, efficacy outcomes may be ham5pered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies have suggested that add-on mistletoe (Viscum album L., VA) improves the quality of life and ameliorates the cytotoxic side effects of standard oncological therapy in cancer patients. The primary objective of this real-world data study was to determine the safety profile of targeted therapy in combination with add-on Helixor® VA therapy compared to targeted therapy alone in breast and gynecological cancer patients. METHODS: The present study is a real-world data observational cohort study utilizing demographic and treatment data from the accredited national Network Oncology (NO) registry. The study has received ethics approval. The safety profile of targeted therapies with or without Helixor® VA therapy and safety-associated variables were evaluated by univariate and adjusted multivariable regression analyses. RESULTS: All stages of breast and gynecological cancer patients (n = 242) were on average 54.5 ± 14.2 years old. One hundred and sixty patients (66.1%) were in the control (CTRL, targeted therapy) and 82 patients (33.9%) were in the combinational (COMB, targeted plus Helixor® VA therapy) group. The addition of Helixor® VA did not hamper the safety profile (χ2 = 0.107, p-value = 0.99) of targeted therapy. Furthermore, no adverse events and a trend towards an improved targeted therapy adherence were observed in the COMB group. CONCLUSIONS: The present study is the first of its kind showing the applicability of Helixor® VA in combination with targeted therapies. The results indicate that add-on Helixor® VA does not negatively alter the safety profile of targeted therapies in breast and gynaecological cancer patients.

The effect of branched-chain amino acid supplementation on cancer treatment.

Background: Anticancer therapies are associated with significant adverse side effects and few treatments that alleviate symptoms exist. Branched-chain amino acids (BCAAs) have been investigated as an intervention for reducing anticancer therapy side effects, although a review of the literature results has yet to be published. Aim: The current review summarizes evidence surrounding this topic and suggests both support and caution in using BCAAs as a treatment for patients receiving anticancer therapies. Methods: In this review, two literature searches were completed. Google Scholar, PubMed, EBSCOhost, and Cochrane databases were searched using the terms "branched-chain amino acids and cancer" and "BCAA and cancer." Results: Two bodies of evidence emerged: One supporting beneficial effects and the other showing adverse outcomes of BCAA supplementation in patients with cancer. Evidence of benefit was a decrease in malnourishment and unintentional weight loss during and after chemotherapy. Potential harms included the idea cancer cells may utilize BCAAs as a source of energy for growth. Conclusions: Supplementation of BCAAs in individuals with cancer should be implemented cautiously. Those who are severely malnourished due to anticancer therapy may benefit the most. BCAA supplementation may also be provided once cancer has been destroyed from the individual's body to aid with recovery.

Mobility, bioaccessibility, pollution assessment and risk characterization of potentially toxic metals in the urban soil of Lahore, Pakistan.

The present study is based on the measurement of potentially toxic metal contents employing various extraction methodologies aimed at the evaluation of their mobility, bioaccessibility and bioavailability in the urban soil (n = 56) of Lahore, Pakistan. Selected metal levels in the soil were quantified using flame atomic absorption spectrometry. On the average basis, aqua regia and glycine extracts revealed comparatively higher contents for most of the metals; average concentrations of Fe, Mn, Zn, Pb, Cu, Cr, Co and Cd were found at 1566, 451.1, 114.8, 52.84, 39.15, 24.82, 12.59 and 3.953 mg/kg in aqua regia extract, while in glycine extract the metal levels were found at 579.6, 174.2, 74.72, 49.74, 19.28, 7.103, 4.692 and 3.357 mg/kg, respectively. However, Cd, Pb, Cu and Zn showed significantly higher mobility and bioavailability in the soil, while Co, Fe and Mn were least mobile/bioavailable. The pollution index was assessed in terms of enrichment factor and modified degree of contamination which revealed severe to significant contamination and anthropogenic enrichment of Cd, Pb, Cu and Zn. Multivariate analysis showed mostly anthropogenic contributions for Zn-Cu-Cr-Pb-Cd. Health risk assessment revealed relatively higher exposure of the metals through ingestion, while only minor contributions were noted for inhalation and dermal contact. Hazard quotient index was within the safe limit (< 1.0) in all soil extractions, thereby indicating no significant non-carcinogenic health risks. The incremental lifetime cancer risk for Cr (4.1E-06) through ingestion was comparatively higher than the safe limit which showed significant lifetime cancer risk to the local population.

Association between niacin and mortality among patients with cancer in the NHANES retrospective cohort.

BACKGROUND: The vitamin niacin is used as a lipid-regulating supplement, but it is unknown whether niacin has a positive influence on cancer prognosis. In this study, we examine the relationship between niacin intake and mortality among patients with cancer. METHODS: Our study utilized all available continuous data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Multivariable Cox regression models were applied in order to investigate dietary niacin intake's association with mortality. We compared the survival probability between groups of low and high niacin intake by plotting Kaplan-Meier curves. An analysis of subgroups was used to investigate heterogeneity sources. RESULTS: A total of 3504 participants were included in the cohort, with 1054 deaths. One thousand eight hundred forty-seven participants (52.3%) were female, 2548 participants (73.4%) were white, and the mean age (SE) was 65.38 years (0.32). According to multivariate logistic regression analysis, niacin intake was negatively associated with mortality outcomes in patients with cancer, with P values below 0.05 in all models. In subgroup analyses based on sex, age, and BMI, the association persisted. The Kaplan-Meier curves indicate that high niacin intake groups have better survival rates than low intake groups. Niacin supplementation improved cancer mortality but not all-cause mortality. CONCLUSION: According to our study, higher dietary niacin intake was associated with lower mortality in cancer patients. Niacin supplements improved cancer survival rates, but not all causes of mortality.

Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy.

Importance: Women with epilepsy are recommended high doses of folic acid before and during pregnancy owing to risk of congenital anomalies associated with antiseizure medications. Whether prenatal exposure to high-dose folic acid is associated with increases in the risk of childhood cancer is unknown. Objective: To assess whether high-dose folic acid supplementation in mothers with epilepsy is associated with childhood cancer. Design, Setting, and Participants: Observational cohort study conducted with nationwide registers in Denmark, Norway, and Sweden from 1997 to 2017. Analyses were performed during January 10, 2022, to January 31, 2022. Mother-child pairs were identified in medical birth registers and linked with information from patient, prescription, and cancer registers, as well as with sociodemographic information from statistical agencies, and were categorized by maternal diagnosis of epilepsy. The study population consisted of 3 379 171 children after exclusion of 126 711 children because of stillbirth or missing or erroneous values on important covariates. Exposures: Maternal prescription fills for high-dose folic acid tablets (≥1 mg daily) between 90 days before pregnancy start and birth. Main Outcomes and Measures: First onset of childhood cancer at younger than 20 years. Cox proportional hazards models were used to calculate adjusted hazard ratios with corresponding 95% CIs, adjusted for potential confounders. Cumulative incidence at aged 20 years was used as a measure of absolute risk. Results: The median age at the end of follow-up in the study population of 3 379 171 children was 7.3 years (IQR, 3.5-10.9 years). Among the 27 784 children (51.4% male) born to mothers with epilepsy, 5934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with 18 exposed cancer cases compared with 29 unexposed, producing an adjusted hazard ratio of 2.7 (95% CI, 1.2-6.3), absolute risk if exposed of 1.4% (95% CI, 0.5%-3.6%), and absolute risk if unexposed of 0.6% (95% CI, 0.3%-1.1%). In children of mothers without epilepsy, 46 646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg), with 69 exposed and 4927 unexposed cancer cases and an adjusted hazard ratio of 1.1 (95% CI, 0.9-1.4; absolute risk, 0.4% [95% CI, 0.3%-0.5%]). There was no association between children born to mothers with epilepsy who were prenatally exposed to antiseizure medications, but not high-dose folic acid, and an increased risk of cancer (absolute risk, 0.6%; 95% CI, 0.2%-1.3%). Conclusions and Relevance: Prenatal exposure to high-dose folic acid was associated with increased risk of cancer in children of mothers with epilepsy.

Research on the progress of Traditional Chinese medicine components and preparations on histone deacetylase inhibitors - Like effects in the course of disease treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: During the treatment of diseases, histone deacetylases (HDAC) may have side effects such as strong immune inhibition and drug resistance, which may lead to damage of heart, liver and kidney. Traditional Chinese medicine (TCM) is a valuable and unique resource in China, which has good efficacy and safety. At present, it has been found that Chinese herbal compounds and active ingredients can effectively inhibit the expression of HDAC. Moreover, pharmacological studies have shown that these TCMs have shown therapeutic effects in the treatment of cancer, cardiovascular and cerebrovascular diseases, orthopedic diseases and skin diseases. AIM OF THE REVIEW: This article reviews the mechanism of action of HDAC, and introduces the epigenetic correlation between TCM and HDAC. We expounded the histone deacetylase inhibitor (HDACi)-like inhibitory effect and clinical application of natural drugs, and summarized the research progress of TCM on HDAC in recent years. MATERIALS AND METHODS: We collected relevant information published before March 2022 by searching the literature in various online databases such as PubMed, CNKI, Wanfang Database, Elsevier, Web of Science and China Biomedical Database. Search terms include "HDAC" or "HDACi", as well as "herb" or "herbal ingredient". RESULTS: A large number of studies have proved that many TCMs and their chemical components have the effect of inhibiting HDAC activity, which is highly selective, acts on different HDAC subtypes, and plays a certain therapeutic effect in cancer, cardiovascular and cerebrovascular diseases, orthopedic diseases, skin diseases and other diseases by inhibiting the process of HDAC. DISCUSSION AND CONCLUSIONS: The review of this paper is helpful to understand and excavate the active components of TCM, further explore the role of plant drugs with HDACi-like effect in diseases, and provide ideas for the development of new HDACi.

Aristolochic acid-associated cancers: a public health risk in need of global action.

Aristolochic acids (AAs) are a group of naturally occurring compounds present in many plant species of the Aristolochiaceae family. Exposure to AA is a significant risk factor for severe nephropathy, and urological and hepatobiliary cancers (among others) that are often recurrent and characterized by the prominent mutational fingerprint of AA. However, herbal medicinal products that contain AA continue to be manufactured and marketed worldwide with inadequate regulation, and possible environmental exposure routes receive little attention. As the trade of food and dietary supplements becomes increasingly globalized, we propose that further inaction on curtailing AA exposure will have far-reaching negative effects on the disease trends of AA-associated cancers. Our Review aims to systematically present the historical and current evidence for the mutagenicity and carcinogenicity of AA, and the effect of removing sources of AA exposure on cancer incidence trends. We discuss the persisting challenges of assessing the scale of AA-related carcinogenicity, and the obstacles that must be overcome in curbing AA exposure and preventing associated cancers. Overall, this Review aims to strengthen the case for the implementation of prevention measures against AA's multifaceted, detrimental and potentially fully preventable effects on human cancer development.

Treatment of chemotherapy-induced thrombocytopenia in patients with non-hematologic malignancies.

Chemotherapy-induced thrombocytopenia (CIT) is a common complication of the treatment of non-hematologic malignancies. Many patient-related variables (e.g., age, tumor type, number of prior chemotherapy cycles, amount of bone marrow tumor involvement) determine the extent of CIT. CIT is related to the type and dose of chemotherapy, with regimens containing gemcitabine, platinum, or temozolomide producing it most commonly. Bleeding and the need for platelet transfusions in CIT are rather uncommon except in patients with platelet counts below 25x109/L in whom bleeding rates increase significantly and platelet transfusions are the only treatment. Nonetheless, platelet counts below 70x109/L present a challenge. In patients with such counts, it is important to exclude other causes of thrombocytopenia (medications, infection, thrombotic microangiopathy, post-transfusion purpura, coagulopathy and immune thrombocytopenia). If these are not present, the common approach is to reduce chemotherapy dose intensity or switch to other agents. Unfortunately decreasing relative dose intensity is associated with reduced tumor response and remission rates. Thrombopoietic growth factors (recombinant human thrombopoietin, pegylated human megakaryocyte growth and development factor, romiplostim, eltrombopag, avatrombopag and hetrombopag) improve pretreatment and nadir platelet counts, reduce the need for platelet transfusions, and enable chemotherapy dose intensity to be maintained. National Comprehensive Cancer Network guidelines permit their use but their widespread adoption awaits adequate phase III randomized, placebo-controlled studies demonstrating maintenance of relative dose intensity, reduction of platelet transfusions and bleeding, and possibly improved survival. Their potential appropriate use also depends on consensus by the oncology community as to what constitutes an appropriate pretreatment platelet count as well as identification of patient-related and treatment variables that might predict bleeding.

Opium Use and Cancer Risk: A Comprehensive Systematic Review and Meta-Analysis of Observational Studies.

Background: Epidemiological studies have reported inconsistent associations between opium use and cancer risk. We therefore conducted a systematic review and meta-analysis to investigate the relationship between opium use and cancer risk. Methods: We searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until February 2021 and references of retrieved relevant articles for observational studies that reported the risk of cancer in relation to opium use. Random-effects models were used to calculate pooled effect sizes (ESs) as well as 95% confidence intervals (CIs) for the association between opium use and cancer risk by considering opium doses and types, duration of consumption, and routes of opium use. Results: In total, 21 observational articles, with a total sample size of 64,412 individuals and 6,658 cases of cancer, were included in this systematic review and meta-analysis. Ever opium users, compared with never opium users, had 3.53 times greater risk of overall cancer (pooled ES: 3.53, 95% CI: 2.60-4.79, P ≤ 0.01). This positive association was also seen for some individual types of cancers except for esophageal and colon cancers. Also, we found that higher opium doses and higher duration of consumption were associated with an increased risk of overall and individual types of cancer. However, the associations between opium doses and the risk of head and neck and larynx cancers were not significant. In terms of the routes of opium use, both opium ingestion and smoking were positively associated with the risk of cancer. Regarding opium types, we found that using teriak, but not shireh, could increase the risk of cancer. Conclusions: Our findings showed that opium use, particularly in the form of teriak, is a risk factor for cancer.

Opium, Street Opium, and Cancer Risk.

Opium is defined as the air-dried latex obtained by incision from the unripe capsules of Papaver somniferum L. Opium is a complex mixture that contains approximately 10% morphine and 2% codeine. It is commonly used to prepare opium tinctures for people with chronic diarrhea. Morphine and related opioids are powerful but highly addictive analgesics; designing less addictive opioids is an active area of pharmaceutical research that may lead to significant improvements in chronic pain management. Recently, the International Agency for Research on Cancer (IARC) has classified opium consumption as carcinogenic to humans (Group 1) based on sufficient evidence of carcinogenicity in human studies. However, all human studies analyzed by the IARC Working Group included participants who consumed opium that was mixed, adulterated, and/or contaminated with known and probable human carcinogens (e.g., tarry residues of combusted opium, arsenic, lead, and chromium). The working group considered that these carcinogens were part of the complex mixture that opium is, rather than co-exposure or confounders. No evidence of carcinogenicity was available for pure opium in human, animal, or mechanistic studies. To avoid confusion and concern among health professionals and patients using medicinal opium preparations and in scientists involved in the design and development of new opium derivatives, opium should be classified in Group 3 (not classifiable as to its carcinogenicity to humans). The term 'street opium' could be used to refer to opium that probably contains human carcinogens not present in pure opium and should remain in Group 1 (carcinogenic to humans).

[Deep vein thrombosis and pulmonary embolism : Diagnosis and treatment]. / Beinvenenthrombose und Lungenembolie : Diagnostik und Therapie.

This review summarizes current evidence and guideline recommendations concerning diagnosis and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). For the diagnostic pathway, evidence-based algorithms should be employed, based on the assessment of pretest clinical probability. D­dimer tests may reduce the need for subsequent diagnostic procedures. Clinical management of PE is guided by risk stratification according to early mortality. Lactate levels may be helpful for further risk stratification. The acute treatment of venous thromboembolism (VTE) is commenced with intensified anticoagulation (AC), either with parenteral AC or higher initial doses of apixaban or rivaroxaban. All patients with VTE should receive the anticoagulation maintenance therapy for 3-6 months, while the duration of the subsequent secondary prophylaxis depends on the presumed risk of VTE recurrence and bleeding. Compression therapy is used to prevent postthrombotic syndrome. Acute revascularization procedures are limited to rare special cases. In obese patients up to 150 kg, standard doses of rivaroxaban and apixaban are appropriate. In cancer-associated thromboembolism (CAT), the previous guideline recommendation to use low molecular weight heparin (LMWH) for 3-6 months is now broadened with the recommendation for factor Xa inhibitors, with the caveat for gastrointestinal and urothelial cancer or expected drug-drug interactions with the anticancer treatment. Here, and in unstable clinical situations, LMWH is preferred.