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Purpose: To investigate the effects of exercise training on cancer-related fatigue (CRF) in colorectal cancer survivors. Methods: Randomized controlled trials published between 1 January 2010 and 19 October 2020, selected through online search conducted in PubMed, Scopus, Web of Science, SPORTDiscus and PEDro databases, were included. Eligible trials compared the effect of exercise training interventions, versus non-exercise controls on CRF, in colorectal cancer survivors, during or after treatment. The methodological quality of individual studies was analysed using the Physiotherapy Evidence Database (PEDro) scale. Standardized mean differences (SMD) that were pooled using random-effects models were included as the effect size. In addition, 95% prediction intervals (PI) were calculated. Results: Six trials involving 330 colorectal cancer patients met the inclusion criteria and presented reasonable to good methodological quality. An overall small-to-moderate effect of exercise training on CRF was found (SMD = - 0.29: 95% CI: [- 0.53; - 0.06]; p = 0.01; PI: [- 0.63; 0.04]; low-quality evidence). Subgroup analysis revealed moderate effects of exercise interventions performed during chemotherapy (SMD = - 0.63; 95% CI: [- 1.06; - 0.21]; p = 0.003) and small, non-significant effects, when exercise training was performed after cancer treatment (SMD = - 0.14; 95% CI: [- 0.43; 0.14]; p = 0.32). Steady improvements were achieved when a combination of aerobic plus resistance exercise was used, in interventions lasting 12 to 24 weeks. Conclusion: Exercise training could be regarded as a supportive therapy for the clinical management of CRF in colorectal cancer patients undergoing chemotherapy, but further studies are necessary to clarify the effects of exercise interventions on CRF after cancer treatment. info:eu-repo/semantics/publishedVersion

Although mutation profiling of defined genes is recommended for classification of acute myeloid leukemia (AML) patients, screening of targeted gene panels using next-generation sequencing (NGS) is not always routinely used as standard of care. The objective of this study was to prospectively assess whether extended molecular monitoring using NGS adds clinical value for risk assessment in real-world AML patients. We analyzed a cohort of 268 newly diagnosed AML patients. We compared the prognostic stratification of our study population according to the European LeukemiaNet recommendations, before and after the incorporation of the extended mutational profile information obtained by NGS. Without access to NGS data, 63 patients (23%) failed to be stratified into risk groups. After NGS data, only 27 patients (10%) failed risk stratification. Another 33 patients were re-classified as adverse-risk patients once the NGS data was incorporated. In total, access to NGS data refined risk assessment for 62 patients (23%). We further compared clinical outcomes with prognostic stratification, and observed unexpected outcomes associated with FLT3 mutations. In conclusion, this study demonstrates the prognostic utility of screening AML patients for multiple gene mutations by NGS and underscores the need for further studies to refine the current risk classification criteria. info:eu-repo/semantics/publishedVersion

Ibrutinib, a potent inhibitor of the Bruton tyrosine kinase, has revolutionized the treatment of many B-cell malignancies. Ibrutinib has an established favorable toxicity profile with up to 8 years of experience in clinical trials; however, despite ibrutinib's favorable toxicity profile, dose reductions and treatment discontinuations are becoming more evident in clinical practice, particularly in the setting of specific clinical contexts and patient characteristics. This manuscript is set to provide practical recommendations on the management of patients treated with this agent in daily practice.A group of multidisciplinary experts from Portugal met to discuss and highlight practical recommendations, supported on both literature and clinical insights, for the management of the treatment with ibrutinib.Handling of both toxicities and drug-drug interactions during ibrutinib treatment poses several challenges to healthcare providers and can benefit from a multidisciplinary approach. The involvement of specialties, such as cardiology, infectiology and pharmacology, can bring an added value to patient care, not only in anticipating/managing safety issues and dose adjustments but also in enhancing adherence to treatment, ultimately improving the risk/benefit balance.By involving a multidisciplinary group of experts, this work provides a set of key recommendations to optimize care and outcomes for ibrutinib-treated patients. Despite not being a fully comprehensive review on the topic, it is intended as a framework to hematologists and other healthcare professionals who manage these patients in their daily clinical practice.

Case series Patients: Female, 49 • Female, 47 Final Diagnosis: Osteomyelitis by Klebsiella pneumoniae Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Hematology Objective: Rare disease Background: Osteomyelitis (OM) due to carbapenemase-producing Klebsiella pneumoniae (CPKp) is a very rare but severe condition, particularly among patients with hematologic malignancies and stem cell transplant recipients, who are especially at risk of developing nosocomial infections caused by this bacterium. Case Report: We describe 2 cases of acute and chronic OM by CPKp in adults with hematologic disorders. Patient 1, with acute lymphoblastic leukemia, developed bacteremia due to multidrug CPKp after induction chemotherapy. Despite pathogen-directed antibiotic treatment, blood cultures remained positive for CPKp, with an increase in its resistance pattern, and worsening of clinical condition. A pelvic computed tomography revealed air bubbles in the femoral head and ilium, suggestive of OM, and bone culture was positive for pandrug-resistant CPKp. The clinical condition deteriorated rapidly and the patient died. Patient 2, with aplastic anemia, developed multidrug CPKp bacteremia after immunosuppressive therapy, with good response to pathogen-directed antibiotic treatment. Ten months later, she underwent a hematopoietic stem cell transplant, and at the time of neutrophil engraftment, an abscess developed in the right thigh. An extensively drug-resistant CPKp was isolated from the pus, and antibiotics were started, without clinical improvement. A magnetic resonance of the thigh revealed an intraosseous abscess, suggestive of OM, and after debridement surgery and 6 weeks of parenteral antibiotics, she was successfully discharged home. Conclusions: OM due to CPKp is uncommonly reported. These 2 cases illustrate the complex management of OM by CPKp in immunocompromised hematologic patients, and the importance of clinical suspicion for a prompt diagnosis, early treatment, and successful outcome.

This study focuses on the organisational culture oriented to learning in the context of achieving the goals of sustainable development. Its objective is to perceive the positioning of values in the culture of organisations, in learning processes, and their influence on performance. This organisational typology facilitates the acquisition, use, and dissemination of knowledge. They learn on a basis of harmony, convergence, companionship, commitment, responsibility and focused on objectives. Which supports the sustainability of the organisation and its creative innovation processes and Sustainable development of society in general. As a methodology, it resorts to secondary data from several empirical works. It assumes that the organisational culture determines performance. However, this philosophy of learning cannot be viewed incoherently. This is due to the determination of behaviors which establish relationships of interaction, sharing, communication and commitment. It uses the model of contrasting values of the organisational culture by Cameron and Quinn to investigate the typology of organisational culture in Higher Education. Evidence largely confirms that the organisational culture, “Adhocracy” is prevalent in the institutions under analysis and that the “Clan” typology is the second most representative one. As the following analysis confirms, this can help achieve more sustainable development goals. These results illustrate that in learning organisations, not only a single typology is adopted, but various others support a central one.

Background: The development of two different non-Hodgkin lymphomas in the same patient is an unlikely coincidence due to the low prevalence of each malignancy. However, a significantly increased risk of developing a second lymphoma was observed in patients with cutaneous T-cell lymphoma (CTCL) in both population-based and clinic-based data [ 1 ]. Most cases reported describe the occurrence of concomitant lymphomas of discordant B- and T-cell phenotypes, mainly MF and chronic lymphocytic leukemia [ 2 ]. On the opposite, few cases of concomitant systemic and cutaneous B-cell lymphomas have been reported [ 3 , 4 ]. Case 1: A young woman with the diagnosis of three B-cell lymphomas. At 37 years-old, primary cutaneous marginal zone lymphoma (pcMZL) was diagnosed on a right cervical cutaneous nodule and relapsed 3 years later on the temporal region; both lesions were excised. One year later, diffuse large B-cell lymphoma (DLBCL) diagnosis was made on an isolated cervical right lymphadenopathy. She was staged as Ann Arbor stage I and treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) regimen for 6 cycles with complete response (CR). Two years later, the diagnosis of follicular lymphoma was made on a lymph node biopsy. The patient remained with asymptomatic cervical and inguinal lymph node enlargement for 10 years until extra-nodal involvement ensued. At that time, treatment with R-FC (rituximab-fludarabine and cyclophosphamide) followed by radiotherapy achieved partial response (PR). In the following 3 years, follicular lymphoma progressed twice and was retreated with radiotherapy with PR. After 5 years of follow-up, the patient remains asymptomatic without further treatment. Case 2: A patient with two lymphomas of discordant phenotype. The 51 years-old Caucasian man presented at our dermatology clinic with a 10-years history of cutaneous erythematous patches and plaques on the abdomen and upper limbs. The 3 cutaneous biopsies made were consistent with the diagnosis of mycosis fungoides and workup excluded systemic involvement. As such, a diagnosis of mycosis fungoides (MF) stage IB was made. The patient had been observed on another hospital facility 3 months before, when he presented bilateral inguinal lymph node enlargement. The excisional biopsy revealed follicular lymphoma but the pathology examination review of the sample at our hospital diagnosed DLBCL, non-germinal center type, that was staged as Ann Arbor II. He started chemoimmunotherapy with R-CHOP regimen for 6 cycles, leading to CR and a mild improvement on MF (downstaging to IB). The patient is currently on topical steroids for MF and DLBC lymphoma is still on remission after 1 year of follow-up. Conclusions: The occurrence of concomitant systemic and cutaneous lymphomas of discordant or concordant lineages may represent a diagnostic challenge. As the treatment of each lymphoma is often different, their correct identification is critical for optimal management of both diseases.

Beta-lactams are known to cause a wide spectrum of neurotoxic manifestations including epileptic seizures. The neurotoxicity of penicillin was first reported in 1945 by Johnson and Walker and is believed to exert an inhibitory effect on gamma-aminobutyric acid transmission of cortical pyramidal cells, due to its beta-lactam ring structure. Epileptogenicity is also a feature of the semisynthetic beta-lactams including aminopenicillins. In this report, we present a patient with a recurrent history of discrete body twitching/jerks of epileptic nature in the context of amoxicillin exposure. The EEG revealed intermittent generalized short bursts of beta-frequency polyspikes. This electro-clinical picture was reversed by amoxicillin discontinuation.

Background: Pregnancy in women with Type 1 diabetes mellitus (T1DM) is associated with increased complications for both baby and mother; such complications can be reduced with careful pregnancy planning. Preconception care (PCC) enhances pregnancy outcomes by helping women to optimize their glycaemic control, through supportive intervention. However, despite these benefits, the uptake and adherence to PCC is low. This qualitative study aimed to generate a better understanding as to why women may not utilize PCC, by eliciting the views and experiences of women with T1DM in relation to PCC.Methods/sample: A sample of six women of reproductive age with T1DM undertook semi-structured interviews exploring their views on PCC. These interviews were tape-recorded, transcribed (verbatim) and analysed using interpretative phenomenological analysis to elicit themes that explicated the women's orientation and behaviour in relation to PCC.Results: The analysis identified five key themes: the fear of complications (bot...

Introduction Acute Promyelocytic Leukemia (APL) prognosis has largely improved over the past decades and is now the acute leukemia with the highest cure rates. However, its early death rate, which reaches 30% in several real-world studies, is the main obstacle to achieving lifelong remission in most patients. Several reports have suggested a potential role of the Disseminated Intravascular Coagulation (DIC) Score of the International Society of Thrombosis and Hemostasis as a marker of bleeding and death in APL. Since the APL-induced coagulopathy and hyperfibrinolysis are responsible for most early deaths, a method to assess the severity of the coagulopathy could guide the daily patient management and the intensity of the blood products used. We aimed to test the hypothesis of whether the improvement of the DIC Score through coagulopathy support can improve the rate of early death in APL. Methods This retrospective, single-center study, included consecutively admitted patients with newly diagnosed genetically confirmed Acute Promyelocytic Leukemia between 2000 and 2020, who were treated with ATRA + anthracycline protocols and prednisolone 0.5 mg/kg differentiation syndrome prophylaxis. All patients received platelets, fibrinogen, and/or fresh frozen plasma according to published clinical indications. Baseline demographics and clinical data were collected, and the DIC Score was calculated at diagnosis and after 48 hours for each patient, using fibrinogen, platelets, prothrombin time and d-dimers. "DIC Score improvement" was defined as an increase of ≥1 point in the calculated score at 48 hours; a stable or decreasing score were considered "no-improvement". A 30-day follow-up for each patient was conducted, and any death during this period was considered in the early-death group. Statistical analysis was performed using Stata, with chi-square test and Mann-Whitney test for differences between groups, and logistic regression for the analysis of predictors of early death. Results A total of 67 patients were included, after excluding 9 patients for missing coagulation values, 8 for first-line arsenic trioxide treatment, and 7 patients for death within 48 hours of hospital admission. The median age was 53 years (25-82), and 29.9% of patients were aged >60 years old. The 30-day mortality rate for this cohort was 31.3%. Comparing the baseline differences between the two groups, the only statistically significant difference detected was a less frequent improvement of the DIC Score over 48 hours in the early-death group (42.86% versus 76.09% in the remaining patients, p=0.008). There was no difference in the Sanz Risk distribution nor age between the two groups. The univariate analysis of predictors of death in 30 days (logistic regression) yielded age >60 years and 48h-improvement of the DIC Score as potential predictors of death. A multivariate analysis model was built incorporating these 2 variables with the Sanz Risk (the number of events in this study permitted only a 3-variable prognostic model), and it identified age>60 years (OR 4.84 [1.37-17.10]; p=0.014) and the lack of a 48-hour improvement in the DIC Score (OR 5.46 [1.61-18.47]; p=0.006) as independent predictors of early death. In patients under 60 years old, having no improvement in the DIC Score over 48 hours is still associated with almost five times superior odds of 30-day mortality (OR 4.55; p=0.038). Conclusion In this cohort, we identified a lack of DIC Score improvement and age>60 years as independent predictive factors of early death in APL. These findings identified a new independent predictor of early death using a dynamic DIC Score assessment, which is easily accessible and calculated, and illustrate how this score can be applied daily in the clinical care of APL patients. Together with the current APL treatment strategies, the intensification of measures to control the leukemia-associated coagulopathy in patients who do not show a DIC Score improvement in the first 48 hours after diagnosis could decrease the early death rate in this otherwise highly-curable leukemia. Disclosures Brioso Infante: Astellas: Speakers Bureau; Novartis: Speakers Bureau.

У рамках даного дослідження узагальнено основні науково-методичні підходи щодо визначення сутності та ролі комунікативних навичок в інноваційній економіці. Головною метою статті є визначення ролі закладів вищої освіти (ЗВО) у формуванні та розвитку комунікативних навичок у студентів, а також визначення напрямів модернізації навчальних програм. Актуальність даного досліджується пояснюється збільшенням кількості випускників ЗВО, які не відповідають наявним запитам та вимогам роботодавців на ринку праці. У рамках дослідження авторами проаналізовано та систематизовано основні методи викладання, що засновані на комплексному процесі навчання та теорії множинного інтелекту, де особлива увага приділяється емоційним, соціальним та громадянським навичкам. Вихідним положенням даного дослідження є аналіз та ідентифікація відмінних та конкурентних навичок освіченого суспільства. Авторами визначено сутність, роль та значення нематеріальних динамічних здібності поряд із традиційним навичками студентів. Визначено, що навчальна програма має бути спрямована на формування навичок у відповідності до концепцій самонавчання (learning to learn) та вмінню забувати вивчене (learning to unlearn). Відповідно до результатів аналізу наукової літератури та сучасних вимог ринку праці, вищенаведені концепції є основною для розвитку інноваційної економіки, адже навчальний процес має бути інтерактивним, когнітивним, емотивно забарвленим, реляційним, емоційним та еволюційним. Автори наголошують, що в даний час особистості потребують оволодіння набором навичок, в якому поєднано навчально-технічні навички із соціальними та емоційними. При цьому емоційні навички повинні доповнюватись мультиплікативними та соціальними здібностями, що сприятиме розвитку внутрішньоособистісних навичок та комунікабельності студентів. Однак автори зазначають, що емоційні та соціальні аспекти у повній мірі не відображені у навчальних планах ЗВО. У статті систематизовано основні слабкі місця випускників ЗВО у відповідності до вимог сучасного ринку праці. Методологічну основу даного дослідження склали аналіз літературних джерел та досліджень з даної тематики. Відповідно до поставленої мети, автори наголошують на необхідності впровадження високоякісного навчального плану, спроможного зменшити існуючі розриви між технічними та комунікативними навичками студентів, з однієї сторони, та підвищити їх конкурентоздатність у майбутньому на ринку праці з іншої сторони. Отримані результати дослідження можуть бути використані ЗВО з метою формування основних цінностей та навичок серед студентів: розуміння та зміцнення їх соціальної позиції у суспільстві, роль та значення їх поведінки, формування навичок співробітництва тощо. This paper summarizes the main arguments within the scientific discussion on the issue of the soft skills in knowledge-based economies. The main purpose of this research is to reflect on the role of Higher Education Institutions in the training of soft skills, as well as to improve the academic curriculum. This subject appears as a consequence of some inadaptability of the graduate students to the working market as referred by employers. This work pretends to draw attention to other teaching-learning methodologies, based on holistic learning and multiple intelligences, where the emotional, social and civic skills are underlined. The starting point is the following question: "which are the distinctive and competitive skills in a knowledge-based society?" and its objectives are: to reflect on intangible dynamic skills, contrasting them to traditional skills, which are mainly based on technical and scientific domains. Therefore, the academic curriculum should be focused on learning to learn and learning to unlearn. According to the literature and the organizations' desires, this is strategic in a based knowledge economy, because learning should be interactive, cognitive, emotive, relational, emotional and evolutionary. Currently, individuals require a skills pack that combines technical-scientific skills with those which support instrumentals, such as social and emotional skills. The latest is the additive with multiplicative properties of professional and social performance and which facilitate the consolidation of both intrapersonal and interpersonal skills. However, as the emotional and social aspects have not been enhanced in higher education curriculum projects, the present study aims to identify frailties in graduate students regarding distinctive skills in a knowledge-based society. The methodological tools of the research are based on the literature review, and on some developed works on the subject. According to this purpose, we pretend to underline the need towards the superior academic curriculum in order to decrease the existing gap between the technical and soft skills and on the other hand to improve the workers' performance. This work also reflects on the skills available on offer at higher education, with the aim to identify relational, social and emotional skills in graduate students. The results of the research can be useful for society in general, because it allows improving values such as attitudes, behaviours, relationships, engagement, ethics, responsibility, performance, among others.

MABLE investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabine-ineligible patients with chronic lymphocytic leukemia. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every four weeks for six cycles. Rituximab plus chlorambucil-treated patients without a complete response after Cycle 6 received chlorambucil monotherapy for at least six additional cycles or until complete response. The primary endpoint was complete response rate (confirmed by bone marrow biopsy) after Cycle 6 in first-line patients. Secondary endpoints included progression-free survival, overall survival, minimal residual disease, and safety. Overall, 357 patients were randomized (rituximab plus bendamustine, n=178; rituximab plus chlorambucil, n=179; intent-to-treat population), including 241 first-line patients (n=121 and n=120, respectively); 355 patients received treatment (n=177 and n=178, respectively; safety population). In first-line patients, complete response rate after Cycle 6 (rituximab plus bendamustine, 24%; rituximab plus chlorambucil, 9%; P=0.002) and median progression-free survival (rituximab plus bendamustine, 40 months; rituximab plus chlorambucil, 30 months; P=0.003) were higher with rituximab plus bendamustine than rituximab plus chlorambucil. Overall response rate and overall survival were not different. In first-line patients with a complete response, minimal residual disease-negativity was higher with rituximab plus bendamustine than rituximab plus chlorambucil (66% vs. 36%). Overall adverse event incidence was similar (rituximab plus bendamustine, 98%; rituximab plus chlorambucil, 97%). Rituximab plus bendamustine may be a valuable first-line option for fludarabine-ineligible patients with chronic lymphocytic leukemia. clinicaltrials.gov identifier: 01056510

This phase 2 study evaluated whether substituting bortezomib for vincristine in frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy could improve efficacy in non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL), centrally confirmed by immunohistochemistry (Hans method). In total, 164 patients were randomized 1:1 to receive six 21-day cycles of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), and doxorubicin 50 mg/m(2), all IV day 1, prednisone 100 mg/m(2) orally days 1-5, plus either bortezomib 1.3 mg/m(2) IV days 1, 4, 8, 11 (rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib [VR-CAP]; n = 84) or vincristine 1.4 mg/m(2) (maximum 2 mg) IV day 1 (R-CHOP; n = 80). There were no significant differences between VR-CAP and R-CHOP in complete response rate (64.5%, 66.2%; odds ratio [OR], 0.91; P = .80), overall response rate (93.4%, 98.6%; OR, 0.21; P = .11), progression-free survival (hazard ratio [HR], 1.12; P = .76), or overall survival (HR, 0.89; P = .75). Rates of grade ≥3 adverse events (AEs; 88%, 89%), serious AEs (38%, 34%), discontinuations due to AEs (7%, 3%), and deaths due to AEs (2%, 5%) were similar with VR-CAP and R-CHOP. Grade ≥3 peripheral neuropathy rates were 6% and 3%, respectively. VR-CAP did not improve efficacy vs R-CHOP in non-GCB DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT01040871.

The safety of obinutuzumab, alone or with chemotherapy, was studied in a non-randomized, open-label, non-comparative, phase IIIb study (GREEN) in previously untreated or relapsed/refractory chronic lymphocytic leukemia. Patients received obinutuzumab 1000 mg alone or with chemotherapy (investigator’s choice of fludarabine-cyclophosphamide for fit patients, chlorambucil for unfit patients, or bendamustine for any patient) on days 1, 8 and 15 of cycle 1, and day 1 of cycles 2–6 (28-day cycles), with the cycle 1/day 1 dose administered over two days. The primary end point was safety/tolerability. Between October 2013 and March 2016, 972 patients were enrolled and 971 treated (126 with obinutuzumab monotherapy, 193 with obinutuzumab-fludarabine-cyclophosphamide, 114 with obinutuzumab-chlorambucil, and 538 with obinutuzumab-bendamustine). Grade ≥3 adverse events occurred in 80.3% of patients, and included neutropenia (49.9%), thrombocytopenia (16.4%), anemia (9.6%), and pneumonia (9.0%); rates were similar in first-line and relapsed/refractory patients, and in first-line fit and unfit patients. Using expanded definitions, infusion-related reactions were observed in 65.4% of patients (grade ≥3, 19.9%; mainly seen during the first obinutuzumab infusion), tumor lysis syndrome in 6.4% [clinical and laboratory; highest incidence with obinutuzumab-bendamustine (9.3%)], and infections in 53.7% (grade ≥3, 20.1%). Serious and fatal adverse events were seen in 53.1% and 7.3% of patients, respectively. In first-line patients, overall response rates at three months post treatment exceeded 80% for all obinutuzumab-chemotherapy combinations. In the largest trial of obinutuzumab to date, toxicities were generally manageable in this broad patient population. Safety data were consistent with previous reports, and response rates were high. (clinicaltrials.gov identifier: 01905943).

Aim: To compare chemotherapy-induced nausea and vomiting (CINV) incidence with healthcare provider (HCP) estimations, and determine predictors of CINV-related quality of life in patients receiving highly or moderately emetogenic chemotherapy. Methods: A prospective observational study of patients in Portugal was conducted. A logistic regression model was used to predict the individual probability of CINV and compare it with the HCP estimate for each patient using a paired t-test. Quality of life was evaluated using the Functional Living Index of Emesis. Results: A total of 81 patients and ten HCPs participated at five hospitals. HCPs significantly underestimated acute nausea (difference = 38.3%), delayed nausea (difference = 41.1%) (both p < 0.001) and delayed vomiting (difference = 7.15%; p = 0.03) in cycle 1. CINV was the only statistically significant predictor of impaired quality of life. Conclusion: Nausea and delayed emesis are underestimated by HCPs.

Diabetes Mellitus is a public health problem that is on the increase throughout the world, including in Portugal. This paper aims to identify the changing geographic pattern of this cause of death in Portugal and its association with sociomaterial deprivation.This is a transversal ecological study of the deaths by Diabetes Mellitus in Portuguese municipalities in three periods (1989-1993, 1999-2003 and 2006-2010). It uses a Bayesian hierarchical model in order to obtain a smooth standardized mortality ratio and the relative risk of death by Diabetes Mellitus associated to sociomaterial deprivation.In 1989-1993, the highest smooth standardized mortality ratio values were found in coastal urban municipalities (80% of municipalities with smooth standardized mortality ratio ≥ 161, of which 60% are urban); in 2006-2010, the opposite was found, with the highest smooth standardized mortality ratio values occurring in rural areas in southern inland regions (76.9% of municipalities with smooth standardized mortality ratio ≥ 161, of which 69.2% are rural), particularly the Alentejo. The relative risk of death by Diabetes Mellitus increases with vulnerability associated to social and economic conditions in the area of residence, and is significant in the last two periods (relative risk: 1.00; IC95%: 0.98-1.02).Diabetes Mellitus presents a geographic pattern marked by coastal-inland and urban-rural asymmetry. However, this has been altering over the last twenty years. 48% of the population reside in municipalities where the smooth standardized mortality ratio has increased in the last twenty years, particularly in the rural areas of inland Portugal.The highest smooth standardized mortality ratio are currently found in rural municipalities with the highest index of sociomaterial deprivation.Introdução: A Diabetes Mellitus é um problema de saúde pública em crescimento em todo o mundo e também em Portugal. Pretendemos identificar a evolução do padrão geográfico desta causa de morte e a associação com a privação sociomaterial, em Portugal. Material e Métodos: Estudo ecológico transversal dos óbitos por Diabetes Mellitus ocorridos nos municípios portugueses em três períodos (1989-1993, 1999-2003 e 2006-2010). Aplicámos um modelo hierárquico bayesiano, de modo a obter a Razão Padronizada de Mortalidade Suavizada e o Risco Relativo, de mortalidade por diabetes associado à privação sociomaterial. Resultados: Observámos os valores da Razão Padronizada de Mortalidade Suavizada mais elevados, em 1989-1993, nos municípios urbanos do litoral (80% dos municípios com Razão Padronizada de Mortalidade Suavizada ≥ 161, sendo 60% urbanos); em 2006-2010 verificámos o oposto, destacando-se, pelos valores de Razão Padronizada de Mortalidade Suavizada elevados, as áreas rurais localizadas no interior sul do país (76,9% dos municípios com Razão Padronizada de Mortalidade Suavizada ≥ 161 sendo 69,2% rurais), principalmente no Alentejo. O Risco Relativo de mortalidade por Diabetes Mellitus aumenta com o aumento da vulnerabilidade associada às condições sociais e económicas da área de residência, principalmente nos dois últimos períodos (Risco Relativo: 1,00; IC95%: 0,98-1,02). Discussão: A Diabetes Mellitus apresenta um padrão geográfico marcado pela assimetria litoral-interior e urbano-rural, que tem vindo a alterar-se ao longo dos últimos vinte anos, verificando-se uma transição geográfica: 48% da população reside em municípios em que a Razão Padronizada de Mortalidade Suavizada aumentou nos últimos vinte anos, com destaque para as áreas rurais do interior de Portugal. Conclusão: As Razões Padronizadas de Mortalidade Suavizada mais elevadas verificam-se, actualmente, em municípios rurais, com índice de privação sociomaterial mais elevado. Palavras-chave: Demografia; Diabetes Mellitus/epidemiologia; Diabetes Mellitus/mortalidade; Factores Socioeconómicos; Portugal.

Diabetic retinopathy is the leading cause of blindness in adults in Western countries. There are few studies about this microvascular complication in the Portuguese population. The aim of the present study is to establish the relationship between diabetic retinopathy, risk factors and associated conditions, in a group of patients with type 2 diabetes mellitus.We performed a descriptive, transversal and case-control study that included 874 patients - 437 with and 437 without diabetic retinopathy, respectively. Data were collected from electronic medical records, in the Portuguese Diabetes Association with a first consult of Diabetology.The group with retinopathy had significantly higher values of HbA1c, systolic blood pressure and years of diagnosis, compared with the group without retinopathy (p0.05). Regarding the levels of HbA1c, both groups showed more than 70% of patients outside the target value (HbA1c6.5%) but in the subgroup with retinopathy, the percentage of patients in these conditions was higher (91.3%) compared to control group (73.2%) (p0.05). The prevalence of hypertension in the sample was 73%. It was found that the group with retinopathy had a significantly higher prevalence of hypertensive patients (79.6% versus 66.4%) (p0.05). The prevalence of nephropathy was higher in the group with retinopathy (35.6% versus 0.8%) (p0.05).There is a positive correlation between retinopathy and hypertension, glycaemic control and nephropathy. Thus, it is extremely important to control blood pressure and to educate patients about the benefits of a good glycaemic level.

The presence of granulomas in the skin of T-cell lymphoma patients is a rare but well-known phenomenon. The authors present the case of a 44-year-old Caucasian male, with a previously treated peripheral T-cell lymphoma, with cutaneous infiltration and extensive dyschromia on his lower limbs. Skin biopsies revealed the presence of sarcoid granulomas associated with the recurrence of the lymphoma, confirmed by immunostaining and molecular analysis. Although a new scheme of chemotherapy was started, he died 18 months later. There are two different patterns of skin granulomas associated with lymphoma: granulomatous infiltrates admixed with neoplastic cells and cutaneous granulomas constituting a nonspecific manifestation of the underlying lymphoma, but presently there is no evidence supporting their relationship with lymphoma prognosis.

The association between hepatitis C and B-cell non-Hodgkin lymphoma (NHL) has been suggested by several studies. We report the case of a 70 year-old patient with the diagnosis of chronic hepatitis C and splenic lymphoma with villous lymphocytes, who had undergone splenectomy and chemotherapy with fludarabine, with transient effectiveness. He was sent to our Hepatology Clinic for the treatment of hepatitis C, and Pegylated Interferon and Ribavirin were started. He had virological and hematological response (63% of villous lymphocytes in the peripheral blood at the beginning of therapy and 0% at the end). With the suspension of antiviral therapy, recurrence of HCV infection and reappearance of atypical lymphocytes (24%) were observed, and Pegylated Interferon was restarted, with good response. The relationship between viral and hematologic response (remission and relapse) supports the hypothesis that hepatitis C virus has an active role in the pathogenesis of splenic lymphoma with villous lymphocytes. publishersversion published

Aim: To compare the efficacy and safety of sitagliptin vs. glipizide in patients with type 2 diabetes and inadequate glycaemic control [haemoglobin A1c (HbA1c) ≥ 6.5 and ≤10%] on metformin monotherapy. Methods: After a metformin dose titration/stabilization period (≥1500 mg/day), 1172 patients were randomized to the addition of sitagliptin 100 mg q.d. (N = 588) or glipizide 5 mg/day (uptitrated to a potential maximum 20 mg/day) (N = 584) for 52 weeks. The primary analysis assessed whether sitagliptin was non-inferior to glipizide regarding HbA1c changes from baseline at Week 52 using a per-protocol approach. Results: From a mean baseline of 7.5%, HbA1c changes from baseline were −0.67% at Week 52 in both groups, confirming non-inferiority. The proportions achieving an HbA1c < 7% were 63% (sitagliptin) and 59% (glipizide). Fasting plasma glucose changes from baseline were −0.56 mmol/l (−10.0 mg/dl) and −0.42 mmol/l (−7.5 mg/dl) for sitagliptin and glipizide, respectively. The proportion of patients experiencing hypoglycaemia episodes was significantly (p < 0.001) higher with glipizide (32%) than with sitagliptin (5%), with 657 events in glipizide-treated patients compared with 50 events in sitagliptin-treated patients. Sitagliptin led to weight loss (change from baseline =−1.5 kg) compared with weight gain (+1.1 kg) with glipizide [between-treatment difference (95% confidence interval) =−2.5 kg (−3.1, −2.0); p < 0.001]. Conclusions: In this study, the addition of sitagliptin compared with glipizide provided similar HbA1c-lowering efficacy over 52 weeks in patients on ongoing metformin therapy. Sitagliptin was generally well tolerated, with a lower risk of hypoglycaemia relative to glipizide and with weight loss compared with weight gain with glipizide.