Vogiatzis I.,National and Kapodistrian University of Athens |
Vogiatzis I.,Evangelismos Hospital |
Vogiatzis I.,Sotiria Hospital |
Vogiatzis I.,University of West of Scotland |
Zakynthinos S.,Evangelismos Hospital
Journal of Applied Physiology | Year: 2013
Cardiopulmonary rehabilitation is recognized as a core component of management of individuals with congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) that is designed to improve their physical and psychosocial condition without impacting on the primary organ impairment. This has lead the scientific community increasingly to believe that the main effects of cardiopulmonary rehabilitative exercise training are focused on skeletal muscles that are regarded as dysfunctional in both CHF and COPD. Accordingly, following completion of a cardiopulmonary rehabilitative exercise training program there are important peripheral muscular adaptations in both disease entities, namely increased capillary density, blood flow, mitochondrial volume density, fiber size, distribution of slow twitch fibers, and decreased lactic acidosis and vascular resistance. Decreased lactic acidosis at a given level of submaximal exercise not only offsets the occurrence of peripheral muscle fatigue, leading to muscle task failure and muscle discomfort, but also concurrently mitigates the additional burden on the respiratory muscles caused by the increased respiratory drive, thereby reducing dyspnea sensations. Furthermore in patients with COPD, exercise training reduces the degree of dynamic lung hyperinflation leading to improved arterial oxygen content and central hemodynamic responses, thus increasing systemic muscle oxygen availability. In patients with CHF, exercise training has beneficial direct and reflex sympathoinhibitory effects and favorable effects on normalization of neurohumoral excitation. These physiological benefits apply to all COPD and CHF patients independently of the degree of disease severity and are associated with improved exercise tolerance, functional capacity, and quality of life. Copyright © 2013 the American Physiological Society.
Colombel J.F.,University of Lille Nord de France |
Sandborn W.J.,Mayo Medical School |
Reinisch W.,Vienna University Hospital |
Mantzaris G.J.,Evangelismos Hospital |
And 9 more authors.
New England Journal of Medicine | Year: 2010
BACKGROUND: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown. METHODS: In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50. RESULTS: Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P = 0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P = 0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P = 0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P = 0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group. CONCLUSIONS: Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.) Copyright © 2010 Massachusetts Medical Society.
Peyrin-Biroulet L.,French Institute of Health and Medical Research |
Reinisch W.,University of Vienna |
Colombel J.-F.,Mount Sinai School of Medicine |
Mantzaris G.J.,Evangelismos Hospital |
And 6 more authors.
Gut | Year: 2014
Background and aims The Crohn's Disease Activity Index (CDAI) has been criticised due to heavy weighting on subjective clinical symptoms. C-reactive protein (CRP) and endoscopic lesions are objective measures of inflammation. We investigated the relationships between clinical disease activity, CRP normalisation and mucosal healing in Crohn's disease (CD). Methods The Study of Biologic and Immunomodulator Naive Patients in CD trial compared infliximab to azathioprine and to infliximab plus azathioprine in 508 CD patients. Mucosal healing was defined as the absence of mucosal ulceration at the week 26 ileocolonoscopy in a patient who had evidence of ulceration at the baseline ileocolonoscopy. Results 188 patients who had evaluable ileocolonoscopy with evidence of mucosal ulceration at baseline, CDAI scores and CRP values at baseline and week 26 were analysed. Seventy-two of 136 patients (53%) who had a CDAI<150 at week 26 achieved mucosal healing, and 38 of 90 patients (42%) achieved both CRP normalisation (CRP<0.8 mg/dL) and mucosal healing while in clinical remission. The positive predictive value (PPV) and negative predictive value (NPV) of CDAI to detect mucosal healing using 150 as a cut-off for CDAI were 65% and 53%, respectively. The PPV and NPV of CDAI to detect mucosal healing and CRP normalisation using 150 as a cut-off for CDAI were 79% and 42%, respectively. Conclusions Half the patients under azathioprine and/ or infliximab in clinical remission have endoscopic and/or CRP evidence of residual active CD, whereas other patients with endoscopic and CRP normalisation have persistent clinical symptoms. Clinical symptoms as scored by CDAI are not a reliable measure of the underlying inflammation.
Skoura E.,Evangelismos Hospital
International Journal of Endocrinology and Metabolism | Year: 2013
Context: Inherited and sporadic medullary thyroid cancer (MTC) is an uncommon and medically challenging malignancy. Even if the extent of initial surgery is deemed adequate, the recurrence rate remains high, up to 50% in most series. Measurement of serum calcitonin is important in the follow-up of patients with MTC, and reliably reflects the existence of the disease. Evidence Acquisition: There is no single sensitive diagnostic imaging method to reveal all MTC recurrences or metastases. Conventional morphologic imaging methods (U/S, CT, and MRI) and several methods of nuclear medicine have been used for this purpose with variable accuracy. Results: The main role of nuclear medicine imaging is the detection of residual or recurrent tumor in the postoperative follow-up. In this review we present the radiopharmaceuticals used in the diagnosis of MTC recurrence, and comparison among them. Conclusions: The most used radiopharmaceuticals labelled with γ emitters are: Metaiodobenzylguanidine (MIBG), labelled with 131I 123I 111In-pentetreotide (Octreoscan), 99mTc-pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA), and 99mTc-EDDA/HYNIC-Tyr3-Octreotide ( Tektrotyd). The radiopharmaceuticals labelled with a positron-emitting radionuclide (ß+), suitable for positron emission tomography (PET) imaging are: 18F-fluorodeoxyglucose (18F-FDG), 18F-fluorodihydroxyphenylalanine (18F-DOPA), and 68Ga-labelled somatostatin analogues (68Ga-DOTATATE or DOTATOC).
Mantzaris G.J.,Evangelismos Hospital
Digestive Diseases | Year: 2016
In the last 20 years, the advent of anti-tumor necrosis factor alpha (TNFα) biologics has revolutionized the treatment of patients with inflammatory bowel disease (IBD) but the cost of biologic therapy now constitutes a large proportion of all healthcare expenditures. Patent expiration has sparked the healthcare industry's interest in the production of biosimilar (BS) versions of first generation biologics (originators [ORGs]) for market sharing. Having no access to the production line of the ORG, the sponsor of a BS needs to develop his own manufacturing process to produce a highly similar version of the reference product. Similarity in structure, physicochemical properties, biologic activity, efficacy and safety must be demonstrated by a comprehensive comparability exercise that includes the most sensitive in vitro tests, models and clinical condition with pre-defined equivalence margins. Extrapolation of indications, inter-changeability and automatic substitution between BS and ORG depend on a legal framework that varies between different agencies. It is not, therefore, unexpected that marketing authorization by the European Medicines Agency and other regulatory agencies (but not Health Canada) of CT-P13 (Remsima™/Inflectra™) as infliximab (Remicade®) BSs for IBD by indication extrapolation has led to stormy discussions in the IBD community and beyond regarding the scientific adequacy of this decision. However, as we now have to live with BSs, we hope that the impeding automatic substitution in association with post-marketing pharmacovigilance, full traceability, registries and new studies will settle the controversy and will increase the confidence of physicians and patients. A universally adopted legal framework should be implemented because, as expected, the non-anti-TNFα BSs will be soon on the stage. © 2016 S. Karger AG, Basel.
Mantzaris G.J.,Evangelismos Hospital
Best Practice and Research: Clinical Gastroenterology | Year: 2014
Crohn's disease is a life-long idiopathic inflammatory disease which affects the entire gastrointestinal tract and occasionally extra-intestinal organs. CD is thought to result from complex interactions between environmental factors, the gut microbes, and the genetic background and the immune system of the host. In the last decades research on these pathogenetic components, and especially on mucosal immunity, has led to the development of biologic agents and therapeutic strategies that have improved dramatically the treatment of CD but we are still far away from curing the disease. If there is a treatment for CD that will probably evolve through methodical steps towards integrating research on all the components involved in the pathogenesis of CD. This holistic and global approach may aid at unravelling the mysteries of CD and developing novel agents and therapeutic strategies which by targeting multiple pathogenetic pathways and at different stages of disease may lead hopefully to cure. © 2014 Elsevier Ltd. All rights reserved.
Vassiliadi D.A.,Rimini Street |
Tsagarakis S.,Evangelismos Hospital
Nature Reviews Endocrinology | Year: 2011
Endocrine glands are among the organs that most frequently harbor incidentally discovered lesions. Pituitary, thyroid, parathyroid and adrenal incidentalomas are increasingly encountered in everyday practice with variable clinical implications. The major concerns are the risks of malignancy and hormonal hypersecretion mostly in the form of subclinically functioning tumors. Pituitary incidentalomas are usually microadenomas and most of the time clinically unimportant; however, incidentally discovered larger lesions require a more careful diagnostic and therapeutic approach. Thyroid incidentalomas are extremely common; exclusion of malignancy is the main concern in this clinical setting. Although parathyroid adenomas are not uncommon, these lesions are frequently missed owing to their small size and due to clinical unawareness. Adrenal incidentalomas carry a small but finite risk of malignancy. An intriguing challenge regarding incidentally discovered adrenal lesions is that a substantial proportion is associated with hormonal alterations, mainly in the form of subtle cortisol excess. Although still largely controversial, evidence is emerging that so-called subclinical hypercortisolism may not be completely harmless. The best biochemical criterion of subtle cortisol excess remains elusive. Surgical intervention in selected cases results in some beneficial effects, but more data are required in order to routinely support surgery in this clinical setting. This Review provides a brief overview of the prevalence, clinical effect and management of endocrine incidentalomas with a focus on data regarding the diagnostic and therapeutic challenges imposed by incidentally discovered adrenal lesions. © 2011 Macmillan Publishers Limited. All rights reserved.
Papamichael K.,Evangelismos Hospital |
Archavlis E.,Evangelismos Hospital |
Lariou C.,Evangelismos Hospital |
Mantzaris G.J.,Evangelismos Hospital
Journal of Crohn's and Colitis | Year: 2012
Background: Infliximab has shown efficacy at preventing post operative recurrence (POR) of Crohn's disease (CD). This study aimed at evaluating whether adalimumab can prevent and treat POR of CD. Methods: This prospective, single-center, open-label, two-year study included 23 patients who had undergone ileocecal resection for refractory or complicated CD and were at high-risk for POR. Patients received adalimumab from post operative day 14 (Group I, n = 8) or at 6. months post operatively after confirmation of endoscopic recurrence (PO-ER) despite treatment with azathioprine, infliximab, or 5-ASA (patients intolerant to infliximab and azathioprine, Group II, n = 15). Symptom assessment and laboratory tests were performed at monthly visits. Endoscopic findings were graded using the Rutgeerts score (RS) at 6 and 24. months after initiation of adalimumab. Primary end-points were maintenance (group I) or achievement of mucosal healing (Group II). Secondary end-points were prevention of post operative clinical recurrence (PO-CR) (Group I) and endoscopic and clinical improvement (group II). Results: In Group I, PO-ER (RS. ≥. i2) was seen in one patient at 6. months PO, whereas a second patient developed PO-ER and PO-CR after 24. months of treatment. In Group II, all patients had PO-ER whereas 9 (60%) patients had PO-CR at study enrolment; after 24. months of treatment 9/15 (60%) patients achieved complete (RS-i0, n = 3) or near complete (RS-i1, n = 6) mucosal healing and 5/9 (56%) clinical remission. No serious adverse events were reported. Conclusions: This pilot study suggests that adalimumab may prevent PO-ER and treat PO-ER/CR in high risk patients for POR of CD. © 2012 European Crohn's and Colitis Organisation.
Mantzaris G.J.,Evangelismos Hospital
Digestive Diseases | Year: 2014
Patients with IBD and prior cancer are at increased risk of developing recurrent or de novo cancer. Depending on the type of malignancy, risk factors include IBD itself, age, environmental factors, genetic susceptibility and exposure to immunosuppressants (IMS), namely thiopurines, methotrexate and anti-TNFα biologics. The procarcinogenic effect of IMS depends on the type of drug and length of exposure. Thiopurines increase the rates of nonmelanoma skin cancer and lymphomas. Methotrexate is less harmful, but data are scarce. Evidence favoring the 'safety' of anti-TNF monotherapy is weak because most patients have been exposed to combinations of IMS prior to the development of malignancy. Anti-TNFα biologics may promote tumor proliferation and increase the risk of melanomas. Exclusion of these patients from trials with biologics, physician concerns or fear of incident cancers and medicolegal consequences, and patient concerns have led to a paucity of data regarding IMS treatment of patients with a prior malignancy. In the absence of guidelines, IMS should be avoided especially during the first 2 years after commencing cancer therapy. Depending on disease type, location and severity, 5-ASA, antibiotics, enteric nutrition, steroids alone or in combinations, seton placement, and 'curative' or 'diverting' surgery may allow for a crucial drug-holiday period before readministration of IMS. Preventive measures include smoking cessation, UV solar protection, annual skin examination and Pap test. If unavoidable, methotrexate should be the drug of first choice followed by anti-TNFα and then thiopurines. Patients should be managed on a case-by-case basis by a multidisciplinary team of experts. © 2014 S. Karger AG, Basel.
Stefanidis K.,Evangelismos Hospital |
Dimopoulos S.,Evangelismos Hospital |
Nanas S.,Evangelismos Hospital
Respirology | Year: 2011
Until recently, the sonographic visualization of pulmonary and pleural diseases was considered a poorly accessible method, due to the inability of sound to penetrate air-filled lung. Despite its limitations, lung ultrasonography is becoming an important diagnostic tool in a growing number of pathological situations such as pneumonia, atelectasis, interstitial-alveolar syndrome, pulmonary embolism, pneumothorax and pleural effusion. The low sensitivity of CXR and the difficulties of performing CT make this technique invaluable for bedside use in the intensive care unit. Lung ultrasonography is an easily repeatable and radiation-free technique, and therefore, an attractive imaging tool for use on a daily basis, especially in the management of critically ill patients. © 2011 Asian Pacific Society of Respirology.