Peutz-Jeghers syndrome： Diagnostic and therapeutic approach

Peutz-Jeghers syndrome (PJS) is an inherited, autosomal dominant disorder distinguished by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous lesions.Prevalence of PJS is estimated from 1 in 8300 to 1 in 280 000 individuals.PJS predisposes sufferers to various malignancies (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular tumors).Bleeding, obstruction and intussusception are common complications in patients with PJS.Double balloon enteroscopy (DBE) allows examination and treatment of the small bowel.Polypectomy using DBE may obviate the need for repeated urgent operations and small bowel resection that leads to short bowel syndrome.Prophylaxis and polypectomy of the entire small bowel is the gold standard in PJS patients.Intraoperative enteroscopy (IOE) was the only possibility for endoscopic treatment of patients with PJS before the DBE era.Both DBE and IOE facilitate exploration and treatment of the small intestine.DBE is less invasive and more convenient for the patient.Both procedures are generally safe and useful.An overall recommendation for PJS patients includes not only gastrointestinal multiple polyp resolution, but also regular lifelong cancer screening (colonoscopy, upper endoscopy, computed tomography, magnetic resonance imaging or ultrasound of the pancreas, chest X-ray, mammography and pelvic examination with ultrasound in women, and testicular examination in men).Although the incidence of PJS is low, it is important for clinicians to recognize these disorders to prevent morbidity and mortality in these patients, and to perform presymptomatic testing in the first-degree relatives of PJS patients.     

Lifestyle modifications to improve musculoskeletal and bone health and reduce disability – A life-course approach

This review covers the evidence relating to lifestye modification in the big three musculoskeletal conditions: osteoarthritis, osteoporosis and rheumatoid arthritis. Lifestyle is of considerable importance in the first two and there is emerging evidence for rheumatoid arthritis despite it not traditionally being considered a lifestyle disease.     

Combined therapeutic approach： Inflammatory bowel diseases and peripheral or axial arthritis

Inflammatory bowel diseases （IBDs）, particularly Crohn＇s disease （CD） and ulcerative colitis （UC）, are associated with a variety of extra-intestinal manifestations （EIMs）. About 36% of IBD patients have at least one EIM, which most frequently affect the joints, skin, eyes and the biliary tract. The EIMs associated with IBD have a negative impact on patients with UC and CD, and the resolution of most of them parallels that of the active IBD in terms of timing and required therapy; however, the clinical course of EIMs such as axial arthritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis is independent of IBD activity. The peripheral and axial arthritis associated with IBD have traditionally been treated with simple analgesics, non-steroidal anti-inflammatory drugs, steroids, sulfasalazine, methotrexate, local steroid injections and physiotherapy, but the introduction of biological response modifiers such as tumor necrosis factor-α blockers, has led to further improvements.     

Neurodegeneration and chronic renal failure in methylmalonic aciduria—A pathophysiological approach

Summary In the last decades the survival of patients with methylmalonic aciduria has been improved. However, the overall outcome of affected patients remains disappointing. The disease course is often complicated by acute life-threatening metabolic crises, which can result in multiple organ failure or even death, resembling primary defects of mitochondrial energy metabolism. Biochemical abnormalities during metabolic derangement, such as metabolic acidosis, ketonaemia/ketonuria, lactic acidosis, hypoglycaemia and hyperammonaemia, suggest mitochondrial dysfunction. In addition, long-term complications such as chronic renal failure and neurological disease are frequently found. Neuropathophysiological studies have focused on various effects caused by accumulation of putatively toxic organic acids, the so-called ‘toxic metabolite’ hypothesis. In previous studies, methylmalonate (MMA) has been considered as the major neurotoxin in methylmalonic aciduria, whereas more recent studies have highlighted a synergistic inhibition of mitochondrial energy metabolism (pyruvate dehydrogenase complex, tricarboxylic acid cycle, respiratory chain, mitochondrial salvage pathway of deoxyribonucleoside triphosphate (dNTP)) induced by propionyl-CoA, 2-methylcitrate and MMA as the key pathomechanism of inherited disorders of propionate metabolism. Intracerebral accumulation of toxic metabolites (‘trapping’ hypothesis’) is considered a biochemical risk factor for neurodegeneration. Secondary effects of mitochondrial dysfunction, such as oxidative stress and impaired mtDNA homeostasis, contribute to pathogenesis of these disorders. The underlying pathomechanisms of chronic renal insufficiency in methylmalonic acidurias are not yet understood. We hypothesize that renal and cerebral pathomechanisms share some similarities, such as an involvement of dicarboxylic acid transport. This review aims to give a comprehensive overview on recent pathomechanistic concepts for methylmalonic acidurias. Competing interests: None declared References to electronic databases: OMIM, ExPASY for EC numbers, KEGG metabolism pathways.     

Recurrent and resistant angina: is the metabolic approach an appropriate answer?

Chronic stable angina is the first manifestation of ischemic heart disease in one half of patients; in the United States, the annual incidence of angina in 213 of 1000 of the population is over 30 years of age. The morbidity associated with ischemic heart disease is considerable: each years millions of patients have an MI, or are hospitalised for unstable angina. In recent years less attention has been paid to chronic ischemic syndrome; a possible explanation is that most patients with angina, refractory to medical treatment, are referred for myocardial revascularization in order to improve symptoms and to prevent death and myocardial infarction. Unfortunately available data do not support this common belief. The current evidence allows us to conclude that percutaneous transluminal coronary angioplasty (PTCA) in chronic coronary artery disease does not reduce the rate of subsequent MI or mortality and that PTCA results in superior symptomatic relief of angina and improved exercise tolerance compared with medical therapy, but the difference narrows with time. Several mechanisms may be considered to explain the persistence of angina/ischemia after a revascularization procedure, including incomplete revascularization, graft/PTCA failure, and disease progression in native coronary arteries. Microvascular dysfunction may play a prominent role in the unexpected prevalence of angina after the removal of obstructions in the major coronary branches. A better understanding of the metabolism derangements associated with ischemia and reperfusion allowed the development of new pharmacological approaches. In contrast to classic "hemodynamic" agents, metabolic agents have no hemodynamic, inotropic or chronotropic effect and interfere with cardiac energy metabolism.     

Uncrossable and undilatable lesions—A practical approach to optimizing outcomes in PCI

Uncrossable lesions are those that cannot be crossed with a balloon after successful guidewire crossing. These lesions are challenging and are commonly encountered in tortuous and calcified arteries as well as chronic total occlusions. They are the second most common barrier to successful PCI in CTO intervention after inability to cross the CTO segment with a guidewire. Procedures involving balloon uncrossable lesions during routine and CTO PCI utilise longer procedural times, radiation dose and contrast volumes with a lower likelihood of procedural success. In this article, we describe a pragmatic approach of managing balloon uncrossable lesions utilising the most contemporary equipment available in an algorithmic fashion beginning with simple, cost effective techniques right up to complex strategies for advanced operators. In addition, some of these lesions, even when crossed by any technique, they may remain difficult to dilate and prepare for stent insertion. We describe an approach of how to manage these undilatable lesions.     

Diagnostic approach to faecal incontinence: What test and when to perform?

Faecal incontinence (FI) is a debilitating common end result of several diseases affecting the quality of life and leading to patient disability, morbidity, and increased societal burden. Given the various causes of FI, it is important to assess and identify the underlying pathomechanisms. Several investigatory tools are available including high-resolution anorectal manometry, transrectal ultrasound, magnetic resonance imaging, and electromyography. This review article provides an overview on the causes and pathophysiology of FI and the author’s perspective of the stepwise investigation of patients with FI based on the available literature. Overall, high-resolution anorectal manometry should be the first investigatory tool for FI, followed by either transrectal ultrasound or magnetic resonance imaging for anal internal sphincter and external anal sphincter injury, respectively.     

How should clinicians and patients choose antihyperglycemic agents?: an evidence-based approach

The choice of antihyperglycemic agents has become more complex as new drug classes have appeared and evidence about their efficacy and safety accumulates. Unfortunately, direct and fair comparisons are lacking and the clinician and patient are left to decide among agents with different safety and burden profiles. Furthermore, the relative efficacy of these agents beyond their ability to lower hemoglobin A1c - that is, in their ability to reduce the risk of diabetes complications - remains uncertain. In this sea of uncertainty, interests other than those of the patient actively shape choices. It is our expectation that better evidence, better policy and better decisions will eventually become routine in the care of patients with diabetes.     

An integrated approach to the detection of colorectal cancer utilizing proteomics and bioinformatics

AIM:To find new potential biomarkers and to establishpatterns for early detection of colorectal cancer.METHODS:One hundred and eighty-two serum samplesincluding 55 from colorectal cancer(CRC)patients,35 fromcolorectal adenoma(CRA)patients and 92 from healthypersons(HP)were detected by surface-enhanced laserdesorption/ionization mass spectrometry(SELDI-MS).Thedata of spectra were analyzed by bioinformatics tools likeartificial neural network(ANN)and support vector machine(SVM).RESULTS:The diagnostic pattern combined with 7 potentialbiomarkers could differentiate CRC patients from CRA patientswith a specificity of 83%,sensitivity of 89% and positivepredictive value of 89%.The diagnostic pattern combinedwith 4 potential biomarkers could differentiate CRC patientsfrom HP with a specificity of 92%,sensitivity of 89% and positivepredictive value of 86%.CONCLUSION:The combination of SELDI with bioinformaticstools could help find new biomarkers and establish patternswith high sensitivity and specificity for the detection of CRC.Yu JK,Chen YD,Zheng S.An integrated approach to thedetection of colorectal cancer utilizing proteomics andbioinformatics.World J Gastroenterol 2004;10(21):3127-3131http://www,wjgnet.com/1007-9327/10/3127,asp     

Heart failure in elderly: which progresses in clinical evaluation and therapeutic approach?

Chronic heart failure (CHF) represents a major and growing health problem, due to its high incidence and prevalence, its poor prognosis and its impact on health-care costs. Although CHF patients are mainly elderly, few studies were aimed at testing the efficacy of diagnostic and therapeutic approaches in this population. The difficulty in CHF diagnosis among the elderly is related to different factors, such as: the frequent presence of co-morbidity conditions mimicking or masking heart failure signs and symptoms; the different diagnostic cut-offs of natriuretic peptides; and the need to correctly evaluate diastolic function in order to assess CHF with preserved ejection fraction. Furthermore, the therapy of elderly CHF patients has not been well defined, considering the few studies involving very aged patients and the absence of a therapeutic strategy demonstrated to improve prognosis of CHF patients with preserved ejection fraction. The aim of this review is to focus on the most recent issues concerning the diagnosis and therapy of elderly patients affected by CHF.     

Interference between PARPs and SIRT1: a novel approach to healthy ageing?

Poly(ADP-ribosyl) polymerases (PARPs) have traditionally been linked to chromosome maintenance and DNA repair. Recent findings identify PARPs as key modulators of metabolism through their influence on SIRT1 activity, hinting to a possible role of PARPs as longevity regulators.     

Telangiectasias associated with reticular veins. Sclerotherapy or combined sclerotherapeutic and surgical approach?

BACKGROUND: We compare the results obtained with sclerotherapy or combined surgical and sclerotherapic approach in two groups of patients, affected by reticular veins-related telangiectasias without incompetence of the saphenous systems or perforating veins. METHODS: 44 female patients were evaluated at our Institution. The first group (21 patients) was treated with sclerotherapy (polidocanol at a concentration of 1% for the reticular veins and 0.25% for the telangiectasias); the second group (23 patients) was treated with a combined approach (ambulatory phlebectomy according to Müller and sclerosis using polidocanol at a concentration of 0.25%). Six and twelve months after surgery or sclerotherapy, we evaluated the appearance of hyperpigmentation or telangiectatic matting, and the recurrence of the treated vessels. RESULTS: In the first group, the hyperpigmentations and the appearance of telangiectatic matting showed, after 6 months, an incidence rate of 14.3% after 12 months, a recurrence of the treated vessels was observed in 4 patients (19%). In the second group, the hyperpigmentations and the appearance of telangiectatic matting showed, after 6 months, an incidence rate of 4.3% at 12 month follow-up no recurrence of treated vessels was observed. CONCLUSIONS: The combined approach might be considered, in selected patients, a valid alternative to sclerotherapy in the treatment of reticular veins-related telangiectasias, particularly in preventing side effects such as hyperpigmentations and telangiectatic matting.     

Gout: can we create an evidence-based systematic approach to diagnosis and management?

The management of gout can be subdivided into four phases. Asymptomatic hyperuricaemia represents the basic underlying metabolic abnormality that can lead to gout. Studies are evaluating whether interventions may be indicated in some cases. Diagnostic criteria for gout and acute flares are still not well defined unless urate crystals are found. Acute attacks of gout are treated with anti-inflammatory measures and the agent of choice is often determined by attack stage, severity and comorbidities that may contra-indicate one or more agents. After attacks subside, there are asymptomatic periods during which decisions must be made about when and how to start urate-lowering measures. If hyperuricaemia persists, there is generally persistence of urate crystals in the joint. Anti-inflammatory prophylaxis is needed when urate-lowering therapy is started. Lifestyle measures should be addressed. If chronic tophaceous gout is diagnosed, urate lowering should be started without delay. New agents are under development that may help with difficult cases.     

The ��parallel pathway��: a novel nutritional and metabolic approach to cancer patients

Cancer-associated malnutrition results from a deadly combination of anorexia, which leads to reduced food intake, and derangements of host metabolism inducing body weight loss, and hindering its reversal with nutrient supplementation. Cancer patients often experience both anorexia and weight loss, contributing to the onset of the clinical feature named as anorexia–cachexia syndrome. This condition has a negative impact upon patients’ nutritional status. The pathogenesis of the anorexia–cachexia syndrome is multifactorial, and is related to: tumour-derived factors, host-derived factors inducing metabolic derangements, and side effects of anticancer therapies. In addition, the lack of awareness of cancer patients’ nutritional issues and status by many oncologists, frequently results in progressive weight loss going undiagnosed until it becomes severe. The critical involvement of host inflammatory response in the development of weight loss, and, in particular, lean body mass depletion, limits the response to the provision of standard nutrition support. A novel nutritional and metabolic approach, named “parallel pathway”, has been devised that may help maintain or improve nutritional status, and prevent or delay the onset of cancer cachexia. Such an approach may improve tolerance to aggressive anticancer therapies, and ameliorate the functional capacity and quality of life even in advanced disease stages. The “parallel pathway” implies a multiprofessional and multimodal approach aimed at ensuring early, appropriate and continuous nutritional and metabolic support to cancer patients in any phase of their cancer journey.