Grave Risk Research Articles

Widespread Misinterpretation of Advance Directives and Portable Orders for Life-Sustaining Treatments Threatens Patient Safety and Causes Undertreatment and Overtreatment.

Widespread Misinterpretation of Advance Directives and Portable Orders for Life-Sustaining Treatments Threatens Patient Safety and Causes Undertreatment and Overtreatment.

Associations between Lipid Profiles and Graves' Orbitopathy can Be HLA-Dependent.

The risk of Graves' orbitopathy (GO) is related to the human leukocyte antigen (HLA) profile and was demonstrated to be increased in patients with elevated total cholesterol (TC) and/or low-density lipoprotein (LDL) cholesterol. We hypothesized that there were some HLA alleles that were related to both GO and TC and/or LDL levels. Therefore, the aim of the study was to compare the TC/LDL results in patients in whom GO-related HLA alleles were present to those in whom they did not occur. HLA classes were genotyped using a next-generation sequencing method in 118 patients with Graves' disease (GD), including 63 and 55 patients with and without GO, respectively. Lipid profiles were assessed at the time of the GD diagnosis. A significant correlation between the presence of GO high-risk alleles (HLA-B*37:01 and C*03:02) and higher TC/LDL levels was found. Additionally, the presence of alleles associated with non-GO GD (HLA-C*17:01 and B*08:01), as well as alleles in linkage disequilibrium with B*08:01 (i.e., HLA-DRB1*03:01 and DQB1*02:01), was correlated with lower TC levels. These results further confirm the significance of TC/LDL in the risk of GO development and provide evidence that associations between TC/LDL and GO can be HLA-dependent.

Increased risk of Graves' orbitopathy following Covid-19 vaccination

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Association between different metabolic phenotypes of obesity and thyroid disorders among Chinese adults: a nationwide cross-sectional study.

Increased body mass index (BMI) and metabolic abnormalities both have potential associations with thyroid disease. The aim of this study was to investigate the correlation between different metabolic phenotypes of obesity and thyroid disorders using nationwide data from China. Data were collected from a cross-sectional survey called the Thyroid Disorders, Iodine Status, and Diabetes Epidemiological Survey conducted between 2015 and 2017 in China. A total of 69007 subjects aged 18 years or older were defined and divided into six groups on the basis of BMI and metabolic health status: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). We estimated the odds ratios (ORs) and confidence intervals [CIs] for different thyroid disorders according to metabolic phenotypes using multivariate logistic regression models. In our study, we found that the prevalence of subclinical hypothyroidism was almost as high in the MUNW group as in the MUO group, the prevalence of overt hyperthyroidism was highest in the MUNW group and Graves' disease was highest in the MHO group. Our results also suggested that the prevalence of goiter and thyroid nodules increased with increased BMI values and that the MUO group had the highest incidence. Multivariate logistic regression analysis indicated that subjects with unhealthy metabolic phenotypes (MUNW, MUOW, and MUO) all had an increased risk of subclinical hypothyroidism, regardless of their BMI. MUNW subjects had an approximately 1.6-fold higher risk of overt hyperthyroidism and a 1.8-fold higher risk of Graves' disease than their metabolically healthy counterparts (MHNW). The present study also demonstrated that the MUO group had the highest risk of goiter and thyroid nodules among the metabolic phenotypes of obesity. Based on our study, we found that metabolic abnormalities and obesity play different roles in various thyroid diseases. Metabolically unhealthy individuals, both with and without obesity, have a higher risk of thyroid disorders than metabolically healthy individuals without obesity.

Mechanism of Metabolic Response to Hepatectomy by Integrated Analysis of Gut Microbiota, Metabolomics, and Proteomics.

Hepatectomy is a common clinical procedure for the treatment of many liver diseases, and the successful recovery of a patient's liver metabolism and function after surgery is crucial for a good prognosis. The objective of this study was to elucidate the metabolic response to hepatectomy using high-throughput sequencing analysis of 16S rRNA gene, metabolomics, and proteomics data. Fecal and serum samples from beagle dogs were collected on day 0 (LH0), day 7 (LH7), and day 28 (LH28) after laparoscopic partial hepatectomy. Liver tissue samples were taken on LH0 and LH7. Dysbiosis in the fecal microbiota was explored, and host-microbiome interactions based on global metabolic and protein profiles and inflammatory processes were determined. Results showed that the relative abundance of Allobaculum and Turicibacter was decreased and that of Escherichia-Shigella was increased after hepatectomy (P < 0.05); the phenylalanine, tyrosine, and tryptophan biosynthetic pathway, along with the phenylalanine and aminoacyl-tRNA biosynthetic pathway, was significantly associated with liver injury. The serum metabolites l-phenylalanine and l-arginine were useful as biomarkers, and the fecal metabolite l-threonine was a signature target monitor for liver recovery. The proteomics profile revealed 412 significantly different proteins and further highlighted two key signaling pathways (mitogen-activated protein kinase [MAPK] and peroxisome proliferator-activated receptor [PPAR]) involved in the response to liver injury. We systematically explored the metabolic mechanism of liver injury and recovery, providing new insights into effective ways to promote recovery after hepatectomy and improve liver function and long-term survival. These fundamental studies on hepatectomy will provide the basis for future advances in treatment and recovery from common liver diseases. IMPORTANCE As the largest parenchymal organ, the liver is a target for bacterial and viral infections, nonalcoholic fatty liver disease (NAFLD), cirrhosis, cancer, and many other diseases, constituting a serious worldwide problem. The treatment for many of these diseases involves hepatectomy. Here, we show that aberrant inflammatory processes after hepatectomy of the liver as reflected in the association between liver metabolism and gut microbiota create a grave risk. This study investigated the mechanisms of gut microbiota and host metabolism involved in liver injury and recovery after hepatectomy, using proteomics to reveal the mechanisms of postoperative liver injury and a comprehensive multi-omics approach to identify changes in metabolism after hepatectomy.

Coping strategies in mitigating covid-19 pandemic’s effect on farming household income in Osun state, Nigeria

Income of farming households with low socio-economic status is a task in emerging nations, rural parts of Nigeria inclusive. In connection with this, the entrance of Covid-19 pandemic posed a grave risk to the economy of the households. This study, therefore, investigate the coping strategies in mitigating Covid-19 pandemic’s effect on the farming households’ income. Data for the paper were collected from 150 farming household heads, through multistage sampling method, with the use of interview scheduled and analysed using appropriate statistics. The findings showed that many (57.3%) of the respondents were male. The widely practiced coping strategies during the pandemic were rationed spending (=2.63), job diversification (=2.40), reduction in hired labour (=2.36), household food rationing (=2.28) among others. There is substantial relationship between household size (r = 0.075, p = 0.003), annual income (r = 0.033, p = 0.004) and coping strategies practiced at p≤0.005. It was concluded that the pandemic had great effect on the income of the farming household. The study recommends formulation of necessary, effective and urgent policies for assisting and generating fresh employments and revenue producing prospects for affected households.

Potential protective effects of red grape seed extract in a rat model of malathion-induced neurotoxicity.

Exposure to pesticide mixtures used in agricultural practice poses a grave risk to non-target animals. This study aimed to determine whether red grape seed extract (RGSE, which is 95% bioflavonoids and equal to 12,000 mg of fresh red grape seed, and 150 mg of vitamin C) alleviated the changes in brain-derived neurotrophic factor (BDNF) level, acetylcholinesterase activity, oxidative stress, and apoptosis induced by orally administered malathion in a rat model of malathion-induced neurotoxicity. Thirty-two adult male Wistar albino rats were divided into four groups and exposed to malathion with or without 4 weeks of RGSE treatment, treated with RGSE alone, or left untreated as controls. The animals were euthanized 24 h after last treatment. Brain samples were collected to measure acetylcholinesterase, superoxide dismutase (SOD), and caspase 3 activity, total antioxidant capacity (TAC), and BDNF levels. Malathion significantly reduced acetylcholinesterase and SOD activity and TAC and significantly increased caspase 3 activity. In comparison, acetylcholinesterase and SOC activity, BDNF level, and TAC were improved and caspase 3 activity was decreased in the malathion-RGSE group, indicating that RGSE corrected the alterations detected in these biochemical parameters. Oxidative stress and apoptosis in the brains of rats exposed to oral malathion were substantially controlled by RGSE treatment.

Right to Food and Geoengineering

Climate change poses grave risks to food security, and mitigation and adaptation actions have so far been insufficient to lessen the risk of climate-induced violations of the right to food. Could safeguarding the right to food, then, justify some forms of geoengineering? This article examines geoengineering through the analytical lens of the right to food. We look at the components of food security and consider how the acceptability of geoengineering relates to the right to food via its impacts on these components. Our examination shows that results vary greatly between different forms of geoengineering: while some forms of geoengineering fail to respect the right to food, certain other forms may even become obligatory to protect the right to food. It appears that there is no support for aerosol-based solar radiation management, whereas some carbon dioxide removal methods can help protect or promote the right to food. The ethical challenges related to carbon dioxide removal methods are, we note, similar to those that will also be faced in the course of climate change mitigation.

Open Letter to the Pontiff and Vatican Cardinals on Pervasively Corrupt Earth, Planetary, and Astrophysical Science

Five hundred years ago the Roman Catholic Church wrongly opposed science. In my fifty years as a scientist, I have observed the Catholic Church reaching out to science, wholly unaware of widespread corruption and cartel-like behavior under guise of science, which leads, I allege, to the Vatican aiding and abetting activities that are not only anti-Christian, but which pose grave risks to human and environmental health.

Prediction of the recurrence risk of Graves' disease after antithyroid drug therapy

Objective: This study aimed at observing the prognostic factors for Graves' disease (GD) recurrence after treatment with antithyroid drugs. Patients and Methods: Clinical data for 247 patients with primary GD hyperthyroidism diagnosed in the endocrinology department of our hospital between March 2014 and February 2017 were collected. Age, sex, thyroid size, thyroid hormone levels, thyrotropin receptor antibody (TRAb), thyroglobulin antibody, thyroid peroxidase antibody, urinary iodine, and other prognostic factors before and after treatment were analyzed and compared. Results: After ATD treatment, 151 cases were in remission and 96 cases were not. The mean age at diagnosis was 37.3 ± 14.0 years in the remission group and 31.2 ± 12.2 years in the nonremission group (P = 0.032). The levels of free triiodothyronine (FT3) in the nonremission group and remission group were 25.7 ± 8.4 and 18.3 ± 9.1 pmol/L, respectively. The proportion of patients with goiter and thyroid-associated orbitopathy was higher in the nonremission group than the remission group. Similarly, both the FT3/FT4 ratio (4.63 ± 1.08 and 3.72 ± 0.69, P= 0.020) and TRAb level (27.4 ± 10.7% and 18.1 ± 9.8%, P= 0.001) significantly increased. Logistic regression analysis indicated that high thyroid volume (odds ratio [OR] =9.647, P= 0.003), high free T3/free T4 ratio (OR = 1.541, P= 0.019), and TRAb level (OR = 1.317, P= 0.002) were independent factors influencing drug treatment failure and were associated with poor prognosis. After drug withdrawal, patients with distinctly enlarged thyroid glands, thyroid-associated eye disease, and low serum thyroid-stimulating hormone (sTSH) levels were higher in the nonremission group than in the remission group. Conclusion: GD patients with goiter, high TRAb level and high FT3/FT4 ratio had poor poor response to drugs. The recurrence rate was high in patients with thyroid-related eye disease, and sTSH delayed recovery.

Emerging Trends of West phobia in Muslim Societies and Islamophobia in Western Societies: Reasons and Remedies

Religion remains a significant source of intolerance, discrimination, and marginalization all across the world, despite efforts to eradicate it. In recent times, religious activities have fostered fear, suspicion, and other bad sentiments among their respective believers, rather than fostering unity and mutual tolerance. In the media, there is a common refrain claiming Islam is the cause of a string of terrorist incidents. Resultantly, various governments are anxious about and mistrust of Muslims (Islamophobia), and on the other side, a western phobia is on the increase. This paper systematically reviews the aspects of Islamophobia and western phobia that have repercussions for peace in the world and peaceful coexistence. According to the findings of the study, an increase in Islamophobic attacks and religious intolerance around the world has presented a grave risk to global concord and unity.

Novel Insight into Non-Genetic Risk Factors of Graves' Orbitopathy.

An assessment of the risk of Graves' orbitopathy (GO) is an important challenge in Graves' disease (GD) management. The purpose of this study was to compare non-genetic parameters in GD patients with and without GO in order to find novel risk factors and to verify the factors already reported. A total number of 161 people, 70 with GO and 91 non-GO patients were included in this study. GO was confirmed to be associated with smoking, older age, higher TSH receptor antibodies (TRAb) and lower thyroglobulin antibody (TgAb) levels and hypercholesterolemia. We demonstrated the latter correlation even for only a mild increase in LDL cholesterol. Importantly, our study provides novel potential GO risk factors, including higher serum creatinine levels, higher MCV and lower PLT. If further confirmed, these new, simple and easily accessible potential GO markers may constitute valuable auxiliary markers in GO risk assessments. We additionally proved that in moderate to severe GO, gender-related differences attenuate. No impact of vitamin D deficiency in GO development in patients with 25-hydroxyvitamin D [25(OH)D] > 20 ng/mL was found. The present report provides a set of GO risk factors, which can be used as a precise tool for an individual GO risk assessment.

The expanding role of expert psychological evaluations and testimony in Hague child abduction litigation

AbstractHague Convention cases are a growing niche in forensic assessments. These cases focus on returning children, or preventing their return, after international abductions, by one of the parents, has occurred. This article focuses on the legal underpinnings of the Hague Abduction Convention, the “affirmative defenses” that may be invoked to prevent a return order, including “grave risk of harm,” “mature objection”, and the “well settled defense.” The article will also focus on the increasing roles that forensic evaluators play in these matters, the distinction between the role of forensic experts in custody proceedings and Hague cases, and the inherent limitations present in these unique kinds of evaluations.

Fundoscopic Findings in Pregnancy Related Hypertensive Disorders and Its Association with Maternal and Fetal Outcomes

Objectives: To determine the prevalence of retinal changes in pregnancy-related hypertensive disorders and their association with maternal and fetal outcomes. Introduction: There is a grave risk to both mother and child when hypertensive problems complicate pregnancy. However, hypertensive sort of disorders during pregnancy have been allied to poor maternal and also neonatal outcomes. This research aimed to evaluate effects of hypertensive sort of disorders of pregnancy on both mothers and their unborn children by analyzing the prevalence, causes, and treatment of these conditions. Subjects and methods: BBH Rawalpindi, Inpatient Department of Gynecology and Obstetrics conducted the case-control research during the period from January 2021 to June 2021. In all, 149 patients participated in the research. Because seven patients could not be located, 142 cases were analyzed. Mild class preeclampsia (65.0 instances), severe class preeclampsia (32.0 hot cases), and also eclampsia (one case) were the subcategories used to categorize patients further, according to research. Thirty-one women who were not hypertensive throughout pregnancy were enlisted as controls. Results: Ninety percent of cases manifested with some edema. About a quarter basically patients had proteinuria above 300.0 mg/24 hours (26.76%), nearly half had proteinuria over two g/24 hours (47.18%), and about a quarter had urine protein based excretion of 3.0-5.0 g/24 hours (25.35%). Usually, incidence of specially HELLP (normally hemolysis, increased liver based special enzymes, and also squat platelet tot up) set of symptoms was 2.80%, raised bilirubin levels were seen in 47%, illustration symptoms occurred in 6.4%, vaginal based hemorrhage occurred in 11.30%, in addition to 42.2% of cases involved the central nervous system. It was shown that eclampsia was the cause of mortality in 2.8% of all maternal deaths. 16.9 percent of births were stillbirths, while 4.23 percent of newborns died. Conclusion: Compared to pregnant women with normal blood pressure, those who suffer from hypertensive disorders of pregnancy have a higher risk of having a baby born with complications. Our research did find a declining trend, although it was less than those seen in other studies; this may be because more of our study's births occurred in hospitals. Keywords: Neonatal outcome, maternal outcome, acute renal failure, and the HELLP syndrome

“Responsibility to Protect” and the BRICS: A Decade after the Intervention in Libya

Abstract “Responsibility to protect” (R2P) emerged as a powerful moral and political norm in 2001 signaling a shift away from traditional state sovereignty to human sovereignty. North Atlantic Treaty Organization’s (NATO) 2011 R2P intervention in Libya, however, created controversies giving rise to sharp differences between the BRICS (Brazil, Russia, India, China, and South Africa) and the West over this new humanitarian norm. Major BRICS states officially support R2P to protect humans from mass atrocities but oppose military actions to implement it. This article examines the question why the BRICS states are resistant to R2P military interventions to protect humans at grave risk. In contrast to the general view that sovereignty exclusively lies at the heart of BRICS’ opposition to R2P, this article contends that, in addition to concerns for sovereignty, BRICS’ opposition to R2P military interventions is more accurately explained by the four interrelated factors of ideological rift between BRICS and the West, colonial domination of the Global South by the West, controversies over NATO's Libya episode, and the recent economic rise of the BRICS states. The article concludes that R2P, caught in the crossfires of West versus BRICS’ differing positions, portends little hope for its practical application in future.

Genetic association of leukocyte telomere length with Graves' disease in Biobank Japan: A two-sample Mendelian randomization study.

BackgroundTelomere length (TL) has been recognized to be fundamental to the risk of autoimmune disorders. However, the role of leukocyte TL in Graves’ disease has not yet been fully elucidated. In the study, we exploited the two-sample Mendelian randomization (MR) design to evaluate the causal effect of leukocyte TL on the risk of Graves’ disease.MethodsGenome-wide association study (GWAS) data of leukocyte TL from the Singapore Chinese Health Study (SCHS) cohort and Graves’ disease from Biobank Japan (BBJ, 2176 cases and 210,277 controls) were analyzed. Nine single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for TL. We used the inverse variance weighted (IVW) approach as the main estimator and MR-Egger regression, weighted median, simple mode, and weighed mode methods as complementary estimators. Horizontal pleiotropy was assessed using the intercept from MR-Egger.ResultsThe analysis demonstrated that genetically predicted longer leukocyte TL was causally associated with a lower risk of Graves’ disease using the IVW method (odds ratio [OR]: 1.64, 95% confidence interval [CI]: 1.23-2.17, P=2.27e-04, and other complementary MR approaches achieved similar results. The intercept from the MR-Egger analysis provided no noticeable evidence of horizontal pleiotropy (β=0.02, P=0.641). MR-PRESSO method reported no outliers (P=0.266).ConclusionsOur results provided evidence to support a genetic predisposition to shorter leukocyte TL with an increased risk of Graves’ disease. Further studies are warranted to explore the mechanism underlying the association.

Patients with Autoimmune Thyroid Diseases Have Higher Prevalence of Positive Antiphospholipid Antibodies: A Systematic Review and Meta-Analysis.

Introduction Autoimmune thyroid diseases (AITDs) and antiphospholipid syndrome (APS) are commonly seen in childbearing-age women and can lead to recurrent miscarriages. Studies with a relatively small sample size were conducted and concluded inconsistent results on the relationship between AITDs and APS or the presence of antiphospholipid (aPL) antibodies. This meta-analysis aimed to provide evidence on the possible association between AITDs and APL using primary data from all relevant studies. Methods Literature databases including PubMed, Embase, and Cochrane were searched from the time when the databases were established to March 2022. A total of 7 studies that met all inclusion criteria were selected in this meta-analysis, with 475 AITD patients and 764 healthy controls. After data extraction, the pooled odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. Results The risk of positive APL in AITD patients was approximately 3 folds higher in AITD patients compared with those in healthy controls (OR 3.41, 95% CI 2.29–5.08, p < 0.001). There was no significant association between the risk of Graves' disease (GD) and positive APL (OR 9.3, 95% CI 0.10–824.73, p=0.33). The risk of positive APL in patients with Hashimoto's thyroiditis (HT) increased over 2 folds compared with healthy controls (OR 3.35, 95% CI 1.55–7.23, p=0.002). Conclusions The result of this meta-analysis proved that the presence of APL was significantly increased in patients with AITD compared with healthy individuals, especially in patients with Hashimoto's thyroiditis.

A putative causality of vitamin D in common diseases: A mendelian randomization study.

BackgroundsVitamin D is considered as a nutrient protecting individuals against an array of diseases based on observational studies. Such a protective effect, however, has not been demonstrated by randomized controlled trials. This study aims to explore a putative causal role of vitamin D in common diseases through a two-sample Mendelian randomization (MR) framework.MethodsCirculating vitamin D was predicted by 41 genetic variants discovered in European populations. Common diseases were verified through two ways, using information from Japanese patients of Biobank Japan and using information from European patients of FinnGen project. We additionally validated the results by replacing vitamin D-associated instrumental variables (IVs) of European population with that of an independent Japanese population and of an independent Indian population. Inverse-variance weighted method was used as the primary analytical approach while a series of MR methods including MR-Egger regression, weighted median, maximum likelihood, MR-PRESSO and multivariate MR were adopted to guarantee MR model assumptions and to detect horizontal pleiotropy.ResultsGenetically predicted vitamin D was significantly associated with an increased risk of Graves' disease (OR = 1.71, 95%CI: 1.25–2.33, P = 0.001) and cataract (OR = 1.14, 95%CI: 1.03–1.28, P = 0.016); while with a decreased risk of esophageal cancer (OR = 0.66, 95%CI: 0.46–0.93, P = 0.019). This significant causal link between vitamin D and cataract was validated replacing IVs identified in the European population with those from Japanese population. No notable associations of vitamin D with other diseases were observed.ConclusionsOur findings indicate a potential causal role of vitamin D in common diseases, which needs further validation.

Globalisation and economic growth in Africa: New evidence from the past two decades

Background: In the last two decades, the world experienced two overlapping global shocks – that is, the 2008–2009 financial crisis and the COVID-19 lockdowns – with severe social and economic consequences on African economies that have, once again, brought to the fore the intricate role that globalisation plays in economic growth because of grave risks that often accompany it.Aim: We consider three research questions about globalisation: (i) does globalisation heighten economic growth? (ii) is there a statistically significant threshold level of globalisation above which globalisation affects growth differently than at lower levels? (iii) what factors moderate the globalisation-economic growth nexus?Setting: A panel of 47 selected countries from Africa from 2001 to 2018 is under scrutiny.Method: To begin, it applies an overlapping five-year moving average (MA) to smoothen the data. In addition, we employ the revised globalisation index and the two-step systems generalised method of the moment (GMM) in its empirical strategy.Results: We find a largely insignificant relationship between globalisation and economic growth. We attribute these results to Africa’s infinitesimal share – less than 5% – in foreign direct investment (FDI) and global trade, acute infrastructure deficit and the lack of relevant skills that lead to productivity losses and weak performance within the international business ecosystem. We also find, among others, that globalisation is more effective in countries with more gross capital formation, higher population and urban growth rates.Conclusion: For Africa to maximise its growth potential from globalisation, sound policies should be put in place to promote trade, FDI, domestic capital formation and urbanisation. We suggest that future studies investigate the long-run equilibrium relationship between globalisation and economic growth.

A rare incidence of primary Synovial Spindle Cell Sarcoma in a 46-year-old male, successfully managed by surgical intervention-A Case Report.

Introduction and importanceSynovial sarcoma (SS) is a rare form of Soft Tissue Sarcoma (STS) which results from the malignant proliferation of mesenchymal cells. Specific etiologies are not yet known, and its incidence rate ranges between 0.81 and 1.42 per 1 million individuals. Its gender-specific prevalence is almost the same between males and females and it is unique from other subtypes of STS in that it's slow growing and in almost half the cases, patients present with distant metastasis at the time of diagnosis.Case presentationWe present the case of a 46-year-old previously healthy male patient, who complained from a right lower extremity painless bulge, which began to be visibly noticeable by the patient 2 months prior to admission. There were no signs of allocated inflammation nor lower limb ischemia. Radiology revealed an irregular mass formation conformant with neoplasia.Clinical discussionSurgical resection of the mass along with synthetic graft replacement of the concomitant vascular bundle. Histopathological analysis of the resected mass revealed a monophasic synovial spindle cell sarcoma.ConclusionSS is a rare neoplasm poses a grave risk for patients due to its malignant pathophysiology and the wide margin of misdiagnoses. It is pivotal to set-up proper preoperative diagnostic guidelines for it and maintain high clinical suspicion so that we can bring down the high rates of the morbidity and mortality which ensue from this malignancy.