Definition and classification of irritable bowel syndrome: current consensus and controversies

The symptom-based taxonomy of IBS and other functional bowel disorders is based on defined individual symptoms and the co-occurrence of certain symptoms in individuals. Wording of survey questions to accurately reflect the symptoms can be difficult in English, but accomplishing it for non-English-speakers, especially residents of non-Western societies, is an even greater challenge that needs more attention. The potential for misdiagnosis and inappropriate management, including unnecessary surgery, under-scores the need for wider knowledge of typical IBS symptoms by physicians and the collaboration of primary and specialist physicians in patient care.Even though the evolving symptom classification is as evidence-based as its designers can make it, some arbitrariness is inevitable. Population prevalence rates vary widely, depending on diagnostic criteria and other factors, and further work is needed to determine which individuals detected in surveys consider themselves distressed enough to want medical care and why the remaining people do not feel this need. Clearly, more primary care patients should be studied. Physicians should assess clinical trials critically regarding patient recruitment methods and patient features that could influence whether the results are applicable to their patients. The instability of bowel habit subtypes suggests that relatively few patients should expect relief by taking the same motility-active drug regularly for a long time. Long-term, natural history studies of symptoms and health care use are needed. Discoveries of subtle morphologic pathology and disordered physiology are elucidating IBS pathophysiology further, which some experts believe will lead to a more objective, laboratory-based (organic) diagnosis and more effective therapy. The benefit patients will obtain from supplementing a traditional symptom-based, biopsychosocial approach with such findings remains to be determined. The symptom criteria have had important roles in epidemiological studies and characterizing subjects for clinical trials. Many practitioners, however,do not know the typical symptoms or use the criteria, and investigating how physicians diagnose IBS has received scanty attention. It is unknown how many physicians diagnose IBS by exclusion only after extensively testing patients with typical symptoms and no alarm features, but determining this could have important economic and safety implications. There has been little careful validation of the symptom criteria, especially with primary care patients, and no particular criteria are clearly superior for clinical practice,although the Manning and Rome I criteria have been most evaluated and are less restrictive than the Rome II criteria.     

Primary aldosteronism: current knowledge and controversies in Conn's syndrome

Primary aldosteronism has been recognized as a common cause of secondary hypertension, accounting for approximately 10% of the hypertensive population. Screening should be applied in hypertensive patients presenting with one of the following: hypokalemia, refractory hypertension, suggestive family history, or an incidentally detected adrenal mass. The most advocated screening test at present is the aldosterone-to-renin ratio, which has a high sensitivity but low specificity. The specificity increases if patients with low aldosterone concentrations are excluded. Published cut-off values vary depending on the hormone assay and the investigated population. Before screening, antihypertensive treatment, especially aldosterone antagonists and beta-blockers, should be discontinued. A pathologic result requires additional work up to prove mineralocorticoid excess. Subtype differentiation is performed by adrenal venous sampling combined with imaging (CT or MRI). One-third of cases are due to aldosterone-producing adenomas, for which the preferred treatment is laparoscopic adrenalectomy. Bilateral adrenal hyperplasia (idiopathic aldosteronism) underlies two-thirds of cases and requires treatment with aldosterone antagonists. Treatment is started with low doses of spironolactone (25-50 mg once daily), which often results in substantial improvements in hypertension.     

Surgical management of Zollinger-Ellison syndrome: Classical considerations and current controversies

Zollinger-Ellison syndrome(ZES) is characterized by gastric acid hypersecretion causing severe recurrent acid-related peptic disease. Excessive secretion of gastrin can now be effectively controlled with powerful proton pump inhibitors,but surgical management to control gastrinoma itself remains controversial.Based on a thorough literature review, we design a surgical algorithm for ZES and list some significant consensus findings and recommendations:(1) For sporadic ZES, surgery should be routinely undertaken as early as possible not only for patients with a precisely localized diagnosis but also for those with negative imaging findings. The surgical approach for sporadic ZES depends on the lesion location(including the duodenum, pancreas, lymph nodes,hepatobiliary tract, stomach, and some extremely rare sites such as the ovaries,heart, omentum, and jejunum). Intraoperative liver exploration and lymphadenectomy should be routinely performed;(2) For multiple endocrine neoplasia type 1-related ZES(MEN1/ZES), surgery should not be performed routinely except for lesions 2 cm. An attempt to perform radical resection(pancreaticoduodenectomy followed by lymphadenectomy) can be made. The ameliorating effect of parathyroid surgery should be considered, and parathyroidectomy should be performed first before any abdominal surgery for ZES; and(3) For hepatic metastatic disease, hepatic resection should be routinely performed. Currently, liver transplantation is still considered an investigational therapeutic approach for ZES. Well-designed prospective studies are desperately needed to further verify and modify the current considerations.     

Metabolic syndrome, diabetes and cardiovascular events: current controversies and recommendations

Metabolic syndrome is now present in up to 40% of the United States adult population and is associated with a nearly a two fold increase in cardiovascular events, independent of the presence of diabetes mellitus. The concept of the metabolic syndrome as clinical syndrome has recently been challenged, however, and controversy exists as to whether the metabolic syndrome adds to cardiovascular risk above and beyond the sum of its independent metabolic components. Given the epidemic of obesity in both industrialized and third world countries, this issue is of great importance. The current article puts this controversy into perspective and explores the association of metabolic syndrome with both accelerated cardiovascular risk and the risk of development of type 2 diabetes. The pathophysiology of the increased risk of cardiovascular disease in diabetes associated with metabolic syndrome is discussed and the importance of early recognition of metabolic syndrome and potential role of addressing insulin resistance is stressed. Clearly more data is needed, but it is safe to say that metabolic syndrome is a worldwide epidemic in association with central obesity and underlying insulin resistance, which will propel a marked increase in cardiovascular events and diabetes mellitus in the years to come. Further research is needed to understand the role of more aggressive therapy in preventing type 2 diabetes and cardiovascular events in the population.     

Carnitine therapy for the treatment of metabolic syndrome and cardiovascular disease: Evidence and controversies

As the incidence of metabolic syndrome increases, there is also a growing interest in finding safe and inexpensive treatments to help lower associated risk factors. l-carntine, a natural dietary supplement with the potential to ameliorate atherosclerosis, has been the subject of recent investigation and controversy. A majority of studies have shown benefit of l-C supplementation in the metabolic syndrome or cardiovascular risk factors. However, recent work has suggested that dietary l-C may accelerate atherosclerosis via gut microbiota metabolites, complicating the role of l-C supplementation in health.     

Tracheobronchomalacia: current concepts and controversies

Tracheobronchomalacia (TBM) results from weakness of the airway walls and/or supporting cartilage and affects both adult and pediatric populations. Diagnosing TBM is challenging because symptoms are nonspecific and overlap with those of other chronic respiratory disorders. Recent advances in multidetector computed tomography have facilitated the noninvasive diagnosis of TBM, and concurrent advances in management have improved clinical outcomes and created a need for greater awareness of the posttreatment appearance of the airways. This review discusses the physiology, histopathology, epidemiology, and clinical features of TBM; it also describes current methods of diagnosis, available therapies, and postoperative imaging evaluation.     

The post-thrombotic syndrome: current knowledge,controversies, and directions for future research

The post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterized by chronic, persistent pain, swelling and other signs in the affected limb. PTS is common, burdensome and costly. It is likely to increase in prevalence, since despite widespread use of and improvements in the efficacy of thromboprophylaxis, the incidence of DVT has not decreased over time. About 20-50% of patients develop PTS within 1-2 years of symptomatic DVT, and severe PTS, which can include venous ulcers, occurs in 5-10% of cases. Although there is no gold standard for the diagnosis of PTS, the presence of typical clinical features in a patient with previous DVT provides strong supporting evidence. Objective evidence of venous valvular incompetence helps to confirm the diagnosis in symptomatic patients. Preventing ipsilateral recurrence of DVT, by ensuring an adequate duration and intensity of anticoagulation for the initial DVT and by prescribing situational thromboprophylaxis after discontinuation of oral anticoagulants, is likely to reduce the risk of developing PTS. There is no proven role for thrombolysis of the initial DVT to prevent PTS. Daily use of graduated compression stockings after DVT may reduce the risk of PTS, and may prevent worsening of established PTS. Pending the results of ongoing studies, stockings are recommended in patients with persistent symptoms or swelling after DVT. Future research should focus on standardizing criteria for PTS diagnosis, identification of DVT patients at high risk for PTS, and rigorously evaluating the effectiveness of stockings, thrombolysis, and venoactive drugs in preventing or treating PTS.     

Hormone replacement therapy: current controversies

Postmenopausal hormonal therapy is used to manage the climacteric symptoms that impair the quality of life of a substantial number of women. The difficulty is achieving the desired effects with minimal side-effects and no adverse health risks. Fundamental to this is understanding the physiology of oestrogen in women and the metabolism of the therapeutic compounds. Although the effects of oral oestrogen therapy have been studied extensively, there is insufficient evidence to assess adequately the independent effects of progestin use, other oestrogen compounds, differing doses and duration of treatment. We have reviewed some basic concepts of oestrogen physiology and how these relate to exogenous oestrogen administration, the risks of greatest concern, and the role of androgens and newer treatment alternatives.     

Bone marrow transplantation: current controversies

The 1988 UCLA symposium on bone marrow transplantation (BMT) provided a comprehensive overview of the current position of this therapy in its widest sense. Major consideration was given to the role of BMT in the treatment of the acute and chronic leukaemias, with particular reference to the timing of this procedure in these disorders. The use of autologous grafting in haematological and non-haematological malignancy was discussed, and the results of BMT in aplastic anaemia and the inherited immune and metabolic diseases were presented. The prevention and therapy of the major post-transplant complications, cytomegalovirus interstitial pneumonitis and graft-versus-host disease, were the subject of lengthy deliberations as were the related topics of T cell depletion, graft-versus-leukaemia and the use of partially matched related or matched unrelated donors.     

Pituitary radiotherapy: current controversies.

External beam radiotherapy has been used extensively in the management of patients with pituitary disease. However, in view of advances in the techniques of radiotherapy planning and administration, neurosurgery and pharmacological manipulation of the pituitary, there are a growing number of questions and controversies surrounding the current and future use of pituitary radiotherapy in the management of pituitary disease.     

Pancreatic cancer stroma: controversies and current insights

Pancreatic cancer is characterized by a dense stromal response. The stroma includes a heterogeneous mass of cells, including pancreatic stellate cells, fibroblasts, immune cells and nerve cells, as well as extracellular matrix proteins, cytokines and growth factors, which interact with the tumor cells. Previous research has indicated that stromal elements contribute to tumor growth and aggressiveness. However, recent studies suggest that some elements of the stroma may actually restrain the tumor. This review focuses on the complex interactions between the stromal microenvironment and tumor cells, discussing molecular mechanisms and potential future diagnostic and therapeutic approaches by targeting the stroma.     

Weaning from mechanical ventilation: current controversies

As an acute episode of respiratory failure resolves for the patient who is receiving mechanical ventilation, the sometimes difficult task of resuming spontaneous ventilation begins. The resumption of spontaneous ventilation, commonly referred to as weaning, is often difficult for the patient with preexisting lung disease. The purpose of this article is to explore the current controversies related to weaning patients from mechanical ventilation. Patients with chronic obstructive pulmonary disease are used as examples, providing the background for understanding weaning in difficult cases. Weaning is conceptualized as a process of three phases: preweaning, weaning, and extubation. Important considerations during each phase are examined.     

Brugada syndrome: Recent advances and controversies

The Brugada syndrome, first described as a new clinical entity in 1992, is widely recognized today as a form of inherited sudden cardiac arrest. The past 16 years witnessed a progressive increase in the number of reported cases and a dramatic proliferation of articles serving to define the clinical, genetic, cellular, ionic, and molecular aspects of the disease. This article provides a brief overview of recent advances in our understanding of the clinical presentation and molecular and cellular mechanisms and an update of existing controversies.     

Prevalence of the metabolic syndrome in the island of Gran Canaria: comparison of three major diagnostic proposals.

AIMS: The present study was conducted to estimate the prevalence of the metabolic syndrome in a Canarian population, and to compare its frequency as defined by the most commonly used working definitions. METHODS: Cross-sectional population-based study. One thousand and thirty adult subjects were randomly selected from the local census of Telde, a city located on the island of Gran Canaria. Participants completed a survey questionnaire and underwent physical examination, fasting blood analyses, and a 75-g standardized oral glucose tolerance test. The prevalence of the metabolic syndrome was estimated according to the definitions proposed by the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR) and the National Cholesterol Education Program (NCEP), the latter with the original (6.1 mmol/l) and the revised criterion (5.6 mmol/l) for abnormal fasting glucose. RESULTS: The adjusted prevalence of the metabolic syndrome was 28.0, 15.9, 23.0 and 28.2%, using the WHO, EGIR, NCEP and revised NCEP criteria, respectively. The measure of agreement (kappa statistic) was 0.57 between the WHO and the original NCEP definitions, and 0.61 between the WHO and the revised NCEP definitions. After excluding diabetic subjects, the agreement between the EGIR and WHO proposals was fairly good (kappa=0.70), whereas concordance of the EGIR with the original and the revised NCEP definitions was moderate (kappa=0.47 and 0.46, respectively). CONCLUSIONS: Whichever the considered diagnostic criteria, the prevalence of the metabolic syndrome in this area of the Canary Islands is greater than that observed in most other European populations.     

Mechanisms of heme iron absorption： Current questions and controversies

Iron is a critical micronutrient, and iron derived from heme contributes a large proportion of the total iron absorbed in a typical Western diet. Heme iron is absorbed by different mechanisms than non-heme iron, but despite considerable study over many years these mechanisms remain poorly understood. This review provides an overview of the importance of heme iron in the diet and discusses the two prevailing hypotheses of heme absorption; namely receptor mediated endocytosis of heme, and direct transport into the intestinal enterocyte by recently discovered heme transporters. A specific emphasis is placed on the questions surrounding the site of heme catabolism and the identity of the enzyme that performs this task. Additionally, we present the hypothesis that a non- heme iron transport protein may be required for heme iron absorption and discuss the experiences of our laboratory in examining this hypothesis.