Economic burden and health-related quality of life in tenosynovial giant-cell tumour patients in Europe: an observational disease registry.

BACKGROUND: Tenosynovial Giant-Cell Tumour (TGCT) is a benign clonal neoplastic proliferation arising from the synovium, causing a variety of symptoms and often requiring repetitive surgery. This study aims to define the economic burden-from a societal perspective-associated with TGCT patients and their health-related quality of life (HRQOL) in six European countries. METHODS: This article analyses data from a multinational, multicentre, prospective observational registry, the TGCT Observational Platform Project (TOPP), involving hospitals and tertiary sarcoma centres from six European countries (Austria, France, Germany, Italy, the Netherlands, and Spain). It includes information on TGCT patients' health-related quality of life and healthcare and non-healthcare resources used at baseline (the 12-month period prior to the patients entering the registry) and after 12 months of follow-up. RESULTS: 146 TGCT patients enrolled for the study, of which 137 fulfilled the inclusion criteria. Their mean age was 44.5 years, and 62% were female. The annual average total costs associated with TGCT were €4866 at baseline and €5160 at the 12-month follow-up visit. The annual average healthcare costs associated with TGCT were €4620 at baseline, of which 67% and 18% corresponded to surgery and medical visits, respectively. At the 12-month follow-up, the mean healthcare costs amounted to €5094, with surgery representing 70% of total costs. Loss of productivity represented, on average, 5% of the total cost at baseline and 1.3% at follow-up. The most-affected HRQOL dimensions, measured with the EQ-5D-5L instrument, were pain or discomfort, mobility, and the performance of usual activities, both at baseline and at the follow-up visit. Regarding HRQOL, patients declared a mean index score of 0.75 at baseline and 0.76 at the 12-month follow-up. CONCLUSION: The results suggest that TGCT places a heavy burden on its sufferers, which increases after one year of follow-up, mainly due to the healthcare resources required-in particular, surgical procedures. As a result, this condition has a high economic impact on healthcare budgets, while the HRQOL of TGCT patients substantially deteriorates over time.

Prognostic factors in patients with primary cutaneous anaplastic large cell lymphoma: a multicentric, retrospective analysis of the Spanish Group of Cutaneous Lymphoma.

BACKGROUND: Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking. OBJECTIVE: To identify prognostic factors for specific survival in patients with PCALCL. METHODS: Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed. RESULTS: One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P < 0.001). Nodal progression was an independent predictive parameter for shorter survival (P = 0.011). CONCLUSION: Multiple cutaneous lesions at presentation, early skin relapse and nodal progression portrait worse prognosis in patients with PCALCL.

Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammation.

Urolithin A (Uro-A) is an anti-inflammatory and cancer chemopreventive metabolite produced by the gut microbiota from the polyphenol ellagic acid. However, in vivo conjugation of Uro-A to Uro-A glucuronide (Uro-A glur) dramatically hampers its activity. We describe here for the first time the tissue deconjugation of Uro-A glur to Uro-A after lipopolysaccharide (LPS)-induced inflammation, which could explain the systemic in vivo activity of free Uro-A in microenvironments subjected to inflammatory stimuli.

Buckwheat and buckwheat enriched products exert an anti-inflammatory effect on the myofibroblasts of colon CCD-18Co.

Buckwheat (BW) constitutes a good source of bioactive components that show anti-inflammatory effects in vitro and in vivo. The use of functional foods in the prevention and treatment of inflammatory bowel diseases (IBDs) has aroused increasing interest. This study investigates the effect of in vitro digested BW and BW-enriched products (BW-enriched wheat breads, roasted BW groats -fermented and non-fermented-, and BW sprouts) on colon myofibroblasts, the cells involved in the regulation of inflammatory response in the intestine. The cells were treated with different digested-BW products, alone or together with TNF-α (20 ng mL-1), and the effects on the cell migration, mitochondrial membrane potential and cell cycle, processes altered during intestinal inflammation, were investigated. A significant reduction in TNF-α-induced migration (25.5%, p < 0.05) and attenuation of the TNF-α-altered cell cycle (p < 0.05) was observed in myofibroblasts treated with BW-enriched white wheat bread. These results contribute to extend the beneficial effects derived from BW bioactive compounds, and suggest that BW consumption can exert beneficial effects on IBDs.

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study.

BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. CONCLUSIONS: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.

Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematologic abnormalities of sitosterolemia.

Essentials Diagnosis of sitosterolemia, a rare recessive or syndromic disorder, is usually delayed. Peripheral blood smear is extremely useful for establishing the suspicion of sitosterolemia. High-throughput sequencing technology enables the molecular diagnosis of inherited thrombocytopenias. Accurate characterization of sitosterolemia helps us determine appropriate management. SUMMARY: Background Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in the ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PSs) usually result in xanthomas and premature coronary atherosclerosis, although hematologic abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis. Objectives To report two novel ABCG5 variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL. Patient/Methods A 46-year-old female was referred to us with lifelong macrothrombocytopenia. She showed familial hypercholesterolemia-related xanthomas. Molecular analysis was performed with high-throughput sequencing. Plasma PS levels were evaluated with gas-liquid chromatography. The STSL landscape was reviewed with respect to specific online databases and all reports published since 1974. Results A blood smear revealed giant platelets and stomatocytes. Novel compound heterozygous variants were detected in exons 7 (c.914C>G) and 13 (c.1890delT) of ABCG5. The patient showed an increased plasma level of sitosterol. These findings support the diagnosis of STSL. In our review, we identified only 25 unrelated STLS patients who presented with hematologic abnormalities including macrothrombocytopenia. It remains unknown why only some patients develop hematologic abnormalities. Conclusions This is the first Spanish STSL patient to be reported and molecularly characterized. The early diagnosis of STLS is strongly supported by the presence of stomatocytes in blood smears. The definitive diagnosis of STSL by measurement of serum PS levels and molecular analyses prompted the use of ezetimibe therapy.

Influence of donor age in allogeneic stem cell transplant outcome in acute myeloid leukemia and myelodisplastic syndrome.

The impact of donor age in patients with acute myeloid leukemia and myelodysplastic syndrome who underwent allogeneic hematopoietic stem cell transplant (HSCT) remains unclear. In the current study, we evaluate 179 consecutive patients who received an HSCT, from January 2000 to January 2013, in our Institution. Most of the HSCT (91%) were HLA-matched. Patient and donor median age were 51 years (18-69) and 47 years (12-75) respectively, and 81 donors (45%) were older than 50 years. The median follow-up was 38 months (range 1-138), Kaplan-Meier estimated 3-year overall survival (OS) was 63% and disease free survival (DFS) was 56%. Interestingly, patients who received an HSCT from a donor older age (>50 y) showed a poorer OS (51% vs 73%; p=0.01), as well as a higher TRM (20% vs 8%; p=0.038) and higher relapse rate (28% vs 39%; p=0.03). In a stratified subanalysis, 3-year estimated OS was significantly lower among patients undergoing an HSCT from >50 years sibling donors compared to those receiving an HSCT from <50 years unrelated donor (54% vs 72%; p<0.001). In summary, we can conclude that receiving an HSCT from a donor over 50 years old is associated with poorer outcome in patients diagnosed with MDS and AML, and this information may be incorporated into the complex process of donor selection.

Urolithins, ellagitannin metabolites produced by colon microbiota, inhibit Quorum Sensing in Yersinia enterocolitica: Phenotypic response and associated molecular changes.

The mammalian enteropathogen Yersinia enterocolitica produces two main N-acylhomoserine lactones (AHLs) involved in Quorum Sensing (QS)-mediated infection processes, such as virulence, biofilm maturation and motility. Ellagitannin (ET)-rich fruits exhibit anti-QS activity but in vivo effects against intestinal pathogens may be associated to the ETs gut microbiota derived metabolites, urolithin-A (Uro-A) and urolithin-B (Uro-B). In this work we show that urolithins, at concentrations achievable in the intestine through the diet, reduce the levels of N-hexanoyl-l-homoserine lactone (C6-HSL) and N-(3-oxo-hexanoyl)-l-homoserine lactone (3-oxo-C6-HSL) in Y. enterocolitica and inhibit QS-associated biofilm maturation and swimming motility. These inhibitory effects were not associated to downregulation of the expression of some of the genes involved in the synthesis of AHLs (yenI and yenR) or in motility (flhDC, fliA, fleB). Our results suggest that urolithins may exert antipathogenic effects in the gut against Y. enterocolitica and highlight the need to investigate the antipathogenic in vivo properties of plant derived metabolites.

Sensitivity and specificity of digital retinal imaging for screening diabetic retinopathy.

AIMS: To assess the effectiveness of a non-mydriatic digital camera (45 degrees -30 degrees photographs) compared with the reference method for screening diabetic retinopathy. METHODS: Type 1 and 2 diabetic patients (n = 773; 1546 eyes) underwent screening for diabetic retinopathy in a prospective observational study. Hospital-based non-mydriatic digital retinal imaging by a consultant specialist in retinal diseases was compared with slit-lamp biomicroscopy and indirect ophthalmoscopy through dilated pupils, as a gold standard, previously performed in a community health centre by another consultant specialist in retinal diseases. The main outcome measures were sensitivity and specificity of screening methods and prevalence of diabetic retinopathy. RESULTS: The prevalence of any form of diabetic retinopathy was 42.4% (n = 328); the prevalence of sight-threatening including macular oedema and proliferative retinopathy was 9.6% (n = 74). Sensitivity of detection of any diabetic retinopathy by digital imaging was 92% (95% confidence interval 90, 94). Specificity of detection of any diabetic retinopathy was 96% (95, 98). The predictive value of the negative tests was 94% and of a positive test 95%. For sight-threatening retinopathy digital imaging had a sensitivity of 100%. CONCLUSIONS: A high sensitivity and specificity are essential for an effective screening programme. These results confirm digital retinal imaging with a non-mydriatic camera as an effective option in community-based screening programmes for diabetic retinopathy.

[Routine preoperative screening of asymptomatic patients: beliefs and attitudes of anesthesiologists in the Canary Islands, Spain]. / Pruebas preoperatorias rutinarias en población asintomática: opiniones y actitudes de los profesionales en Canarias.

OBJECTIVES: To identify factors that explain anesthesiologists' inappropriate use of preoperative tests in asymptomatic patients scheduled for elective surgery. MATERIAL AND METHODS: A validated questionnaire was sent to anesthesiologists at university hospitals in the Canary Islands. Information about preoperative testing patterns and reasons for selecting tests was gathered. RESULTS: The questionnaire was self-administered by 66 anesthesiologists (68% of the total). Scientific knowledge was not the reason why most respondents ordered preoperative tests in asymptomatic individuals. That was the opinion of 95% of anesthesiologists for chest x-rays, 82% for electrocardiograms, and 68% for laboratory tests. Clinical history and a medical examination gave sufficient information for selecting patients in need of specific tests in the opinion of 77.19% of the respondents. Half did not agree that routine electrocardiograms and laboratory tests should be abandoned. The justification for these tests was coverage of medical malpractice liability for 68.42%. Most considered that the need to order preoperative tests in asymptomatic patients increased after age 40. CONCLUSIONS: Although anesthesiologists admit that their request for preoperative tests in asymptomatic individuals is not supported by scientific evidence, the quest for safety and legal protection from the consequences of potential adverse consequences of providing anesthesia affects the selection of preoperative tests for asymptomatic patients.

Bone mineral density referral for dual-energy X-ray absorptiometry using quantitative ultrasound as a prescreening tool in postmenopausal women from the general population: a cost-effectiveness analysis.

The aim of our study was to assess, from the perspective of the National Health Services in Spain, the cost-effectiveness of quantitative ultrasound (QUS) as a prescreen referral method for bone mineral density (BMD) assessment by dual-energy X-ray absorptiometry (DXA) in postmenopausal women of the general population. Using femoral neck DXA and heel QUS. We evaluated 267 consecutive postmenopausal women 65 years and older and attending primary care physician offices for any medical reason. Subjects were classified as osteoporotic or nonosteoporotic (normal or osteopenic) using the WHO definition for DXA. Effectiveness was assessed in terms of the sensitivity and specificity of the referral decisions based on the QUS measurement. Local costs were estimated from health services and actual resource used. Cost-effectiveness was evaluated in terms of the expected cost per true positive osteoporotic case detected. Baseline prevalence of osteoporosis evaluated by DXA was 55.8%. The sensitivity and specificity for the diagnosis of osteoporosis by QUS using the optimal cutoff thresholds for the estimated heel BMD T-score were 97% and 94%, respectively. The average cost per osteoporotic case detected based on DXA measurement alone was 23.85 euros. The average cost per osteoporotic case detected using QUS as a prescreen was 22.00 euros. The incremental cost-effectiveness of DXA versus QUS was 114.00 euros per true positive case detected. Our results suggest that screening for osteoporosis with QUS while applying strict cufoff values in postmenopausal women of the general population is not substantially more cost-effective than DXA alone for the diagnosis of osteoporosis. However, the screening strategy with QUS may be an option in those circumstances where the diagnosis of osteoporosis is deficient because of the difficulty in accessing DXA equipment.

[Socioeconomic costs of cardiovascular disease and cancer in the Canary Islands (Spain) in 1998]. / Los costes socioeconómicos de las enfermedades cardiovasculares y del cáncer en las Islas Canarias en 1998.

OBJECTIVE: To evaluate the economic impact in terms of direct and indirect costs of the cardiovascular disease and cancer in the Canary Islands in 1998. METHODS: The cost-of-illness method was used. Direct and indirect costs were estimated using prevalence costs, i.e., the costs produced in 1998. Direct costs were divided into hospitalization costs, outpatient costs, primary health care costs, and drug costs while indirect costs were obtained through transformation of physical units into monetary units using the approach of human capital theory and the friction cost method. RESULTS: The total costs of cardiovascular disease and cancer were 246.11 and 193.72 million euros respectively. The direct costs of the two diseases were 134.44 and 58.04 million euros respectively, representing 55% and 30% of total costs and 16% of total health care expenditure in this region. The indirect costs of these two diseases were 111.68 and 135.68 million euros respectively, representing 45% and 70% of total costs. Use of the friction cost method revealed that indirect costs decreased by 88% for cardiovascular disease and those for cancer decreased by 77%. CONCLUSIONS: Although this study adopts a conservative approach by omitting costs associated with pain and suffering, permanent disability, and those of at-home care provided by the family, the annual socioeconomic cost of cardiovascular disease and cancer in the Canary Islands was high, amounting to 440 million euros.

[Preoperative testing routines for healthy, asymptomatic patients in the Canary Islands (Spain)]. / Patrón de utilización de pruebas preoperatorias en una población sana y asintomática en Canarias.

OBJECTIVES: To analyze patterns of routine testing before elective/scheduled surgery in healthy/asymptomatic patients classified as ASA I or II according to the American Society of Anesthesiologists. MATERIAL AND METHOD: A questionnaire on the organization of preoperative testing was completed by anesthesiologists at five public hospitals in the Canary Islands. The questionnaire emphasized the most commonly ordered screening procedures, such as chest X-rays, electrocardiograms, laboratory tests and spirometry. RESULTS: Red cell counts were most frequently requested (for 86% of the patients), followed by platelet counts (80%) and blood chemistry (75%) and coagulation studies (72%). Least requested were urine tests and spirometry. The frequencies of electrocardiogram and chest X-ray requests fell between the two extremes, with patient age and the presence of certain indications seeming to affect whether those tests would be ordered or not. The need for such screening was perceived to increase for patients over 40 years of age. The ordering of preoperative tests varied from hospital to hospital and among anesthesiologists at a single site in spite of established protocols. CONCLUSIONS: Hospitals and individual anesthesiologists differ considerably in how they request preoperative tests. The variations can not be explained solely by differing patient needs given that respondents were contemplating only healthy/asymptomatic individuals undergoing relatively simple procedures.