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- Recurrence Patterns and Timing Courses Following Curative-Intent Resection for Intrahepatic CholangiocarcinomaPublication . Hu, LS; Zhang, XF; Weiss, M; Popescu, I; Pinto Marques, H; Aldrighetti, L; Maithel, S; Pulitano, C; Bauer, T; Shen, F; Poultsides, GA; Soubrane, O; Martel, G; Koerkamp, B; Itaru, E; Pawlik, TBackground: Recurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common. Objective: The aim of this study was to investigate the patterns, timing and risk factors of disease recurrence after curative-intent resection for ICC. Methods: Patients undergoing curative resection for ICC were identified from a multi-institutional database. Data on clinicopathological and initial operation information, timing and first sites of recurrence, recurrence management, and long-term outcomes were analyzed. Results: A total of 920 patients were included. With a median follow-up of 38 months, 607 patients (66.0%) experienced ICC recurrence. In the cohort, 145 patients (23.9%) recurred at the surgical margin, 178 (29.3%) recurred within the liver away from the surgical margin, 90 (14.8%) recurred at extraheptatic sites, and 194 (32.0%) developed both intrahepatic and extrahepatic recurrence. Intrahepatic margin recurrence (median 6.0 m) and extrahepatic-only recurrence (median 8.0 m) tended to occur early, while intrahepatic recurrence at non-margin sites occurred later (median 14.0 m; p < 0.05). On multivariate analysis, surgical margin < 10 mm was associated with increased margin recurrence (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.11-2.60; p = 0.014), whereas female sex (HR 2.12, 95% CI 1.40-3.22; p < 0.001) and liver cirrhosis (HR 2.36, 95% CI 1.31-4.25; p = 0.004) were both associated with an increased risk of intrahepatic recurrence at other sites. Median survival after recurrence was better among patients who underwent repeat curative-intent surgery (48.7 months) versus other treatments (9.7 months) [p < 0.001]. Conclusions: Different recurrence patterns and timing of recurrence suggest biological heterogeneity of ICC tumor recurrence. Understanding timing and risk factors associated with different types of recurrence can hopefully inform discussions around adjuvant therapy, surveillance, and treatment of recurrent disease.
- Bacterial Infections in Patients with Cirrhosis Admitted to the HospitalPublication . Sousa Cardoso, FS
- High-Intensity Interval Training in Cardiac Resynchronization Therapy: a Randomized Control TrialPublication . Santa-Clara, H; Abreu, A; Melo, X; Santos, V; Silva Cunha, P; Oliveira, MM; Pinto, R; Mota Carmo, M; Fernhall, BAIMS: To determine the effects of high-intensity interval training (HIIT) following cardiac resynchronization therapy (CRT) implantation in patients with chronic heart failure (CHF), on noninvasive estimates of systolic ventricular function, exercise performance, severity of symptoms and quality of life. METHODS: Cardiopulmonary exercise testing, resting transthoracic echocardiogram and health-related quality of life assessment were obtained before and at 6 months after CRT implantation in 37 patients with moderate-to-severe CHF. Patients were randomized after CRT to either a 24-week HIIT group (90-95% peak heart rate, 2 days per week) or to a usual care group (CON). Mixed design 2 × 2 repeated measures ANOVA were used to test for differences within and in-between groups. RESULTS: Improvements in health-related quality of life (HIIT = 98.54%, CON = 123.47%), NYHA class (HIIT = 43.44%, CON = 38.30%) HR recovery at minute 1 (HIIT = 32.32%, CON = 42.94%), pulse pressure at peak effort (HIIT = 14.06%, CON = 9.52%, LVEF (HIIT = 42.17%, CON = 51.10%) and LV Mass (HIIT = 13.26%, CON = 11.88%) were similar in both groups (p > 0.05). Significant increases in CPET duration in the HIIT group (25.94%), and increases in peak VO2 (HIIT = 8.64%, CON = 4.85%) and percent-predicted VO2 (HIIT = 10.57%, CON = 4.26%) in both groups, were observed in the intention-to-treat analysis. CONCLUSION: Six months of HIIT in patients in CRT did not further improved indices of functional capacity and health-related quality of life, and LV structure and function, compared to CRT alone. However, HIIT led to further improvements in exercise performance. It remains unclear whether HIIT benefits patients in CRT to a similar degree as more conventional forms of exercise training previously shown to maximize benefits in CRT.
- Prognostic Utility of Albumin-Bilirubin Grade for Short- and Long-Term Outcomes Following Hepatic Resection for Intrahepatic Cholangiocarcinoma: a Multi-Institutional Analysis of 706 PatientsPublication . Tsilimigras, D; Hyer, J; Moris, D; Sahara, K; Bagante, F; Guglielmi, A; Aldrighetti, L; Alexandrescu, S; Pinto Marques, H; Shen, F; Koerkamp, B; Endo, I; Pawlik, TBackground: The objective of the current study was to define the impact of albumin-bilirubin (ALBI) grade on short- as well as long-term outcomes among patients with intrahepatic cholangiocarcinoma (ICC). Methods: Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified using an international multi-institutional database. Clinicopathologic factors including ALBI score were assessed using bivariate and multivariable analyses, as well as standard survival analyses. Results: Among 706 patients, 453 (64.2%) patients had ALBI grade 1, 231 (32.7%) ALBI grade 2, and 22 (3.1%) had ALBI grade 3. After adjusting for all competing factors, patients with ALBI grade 2/3 had higher odds of a prolonged length-of-stay (>10 days, odds ratio [OR] = 2.37, 95% confidence interval [CI]:1.47-3.80), perioperative transfusion (OR = 2.15, 95% CI:1.45-3.18) and 90-day mortality (OR = 2.50, 95% CI:1.16-5.38). Median and 5-year overall survival (OS) for the entire cohort was 41.5 months (IQR:15.7-107.8) and 39.8%, respectively. Of note, median OS incrementally worsened with increased ALBI grade: grade 1, 49.6 months (IQR:18.3-NR) vs grade 2, 29.6 months (IQR:12.6-98.4) vs grade 3, 16.9 months (IQR:6.5-32.4; P < 0.001). On multivariable analysis, higher ALBI grade remained associated with higher hazards of death (grade 2/3: hazard ratio = 1.36, 95% CI:1.04-1.78). Conclusion: The ALBI score was associated with both short- and long-term outcomes following resection for ICC and could prove a useful surrogate marker to identify patients at risk for adverse outcomes.
- CODAP: a Multidisciplinary Consensus Among Portuguese Experts on the Definition, Detection and Management of Atherogenic DyslipidemiaPublication . Mello e Silva, A; Aguiar, C; Sequeira Duarte, J; Couto, L; Teixeira Veríssimo, M; Marques da Silva, PIntroduction and aims: Atherogenic dyslipidemia is an important contributor to residual cardiovascular (CV) risk, but it is underdiagnosed and undertreated. This study aimed to assess the opinion of Portuguese experts to generate a consensus concerning the diagnosis and treatment of atherogenic dyslipidemia, as well as to contribute toward standardization of clinical practice in this disorder. Methods: The study consisted in the application of a questionnaire to an expert panel, following a modified Delphi methodology. Results: The majority (88.4%) of the proposed items were found to be consensual. The expert panel recognized the importance of the atherogenic dyslipidemia phenotype, the role played by low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol as risk markers and therapeutic targets, the choice of statins as first-line lipid-lowering drugs, and the value of associating statins with fenofibrate as a means to reduce residual CV risk. However, the role played by triglycerides in CV risk and the therapeutic value of fibrates lacked consensus. Taking into consideration the state of the art and the opinions expressed in this study, the scientific committee developed a treatment algorithm aimed to improve the perception and treatment of atherogenic dyslipidemia. Conclusions: The experts involved in this study were shown to be familiar with the concept and the importance of atherogenic dyslipidemia. The few situations in which a consensus could not be found were mainly related to the interpretation and/or relevance of the available evidence.
- A Post Hoc Analysis on Rhythm and High Intensity Interval Training in Cardiac Resynchronization TherapyPublication . Melo, X; Abreu, A; Santos, V; Silva Cunha, P; Oliveira, MM; Pinto, R; Mota Carmo, M; Fernhall, B; Santa-Clara, HObjectives. Evaluate the effects of a 6-month High Intensity Interval Training (HIIT) program on (1) functional capacity and health-related quality of life, (2) multiple blood biomarkers, (3) echocardiographic parameters, and (4) exercise performance, in patients in cardiac resynchronization therapy (CRT) stratified by the presence of atrial fibrillation (AF), targeting the following questions: (1) Does CRT provide similar benefits in patients in AF and sinus rhythm (SR)?; and (2) Does HIIT provides similar benefits in patients in AF and SR? Design. Estimates were available at baseline and 6 months after CRT implantation in 37 patients with heart failure. Patients were randomized after CRT to a 24-week HIIT group or to a usual care group (CON). In this sub-analysis, HIIT (AF = 7; SR = 11) and CON (AF = 9; SR = 10) were stratified by the presence of AF. Results. Patients in AF benefitted to a lesser degree from CRT in functional status than patients in SR (23.8-46.0%). However, HIIT induced superior improvements in patients in AF compared to CON (23.9-61.0%). Decreases in TNF-α (8.5-42.9%), BNP (15.3-34.6%) and left ventricular mass (9.6-26.2%) were only observed in patients in SR, whereas increases in peak oxygen uptake were only observed in patients in AF (19.5-23.2%). HIIT improved exercise capacity (8.8-59.4%) in patients in SR. Conclusions. Patients in AF or SR undergoing CRT demonstrated distinct benefits from device implantation and from HIIT as an adjunctive therapeutic strategy. This suggests that both mainstay and adjunctive therapeutics may need to be managed differently in patients in AF and SR.
- A Novel Online Prognostic Tool to Predict Long-Term Survival after Liver Resection for Intrahepatic Cholangiocarcinoma: The "Metro-Ticket" ParadigmPublication . Sahara, K; Tsilimigras, D; Mehta, R; Bagante, F; Guglielmi, A; Aldrighetti, L; Alexandrescu, S; Pinto Marques, H; Shen, F; Koerkamp, B; Endo, I; Pawlik, TBackground: The aim of the current study was to develop an online calculator to predict survival after liver resection for intrahepatic cholangiocarcinoma (ICC) based on the "metro-ticket" paradigm. Methods: Between 1990 and 2016, patients who underwent liver resection for ICC were identified in an international multi-institutional database. The final multivariable model of survival was used to develop an online prognostic calculator of survival. Results: Among 643 patients, actual 5-year overall survival (OS) after resection for ICC was 42.7%. On multivariable analysis, CA19-9 > 200 (hazard ratio (HR), 2.62; 95% CI, 2.01-3.42), sum of the number and largest tumor size >7 (HR, 1.88; 95% CI, 1.46-2.42), N1 disease (HR, 2.87; 95% CI, 1.98-4.16), R1 resection (HR, 1.72; 95% CI, 1.21-2.46), poor/undifferentiated tumor grade (HR, 1.74; 95% CI, 1.25-2.44), major vascular invasion (HR, 1.47; 95% CI, 1.03-2.10), and adjuvant chemotherapy (HR, 0.64; 95% CI, 0.45-0.89) were significantly associated with survival and were included in the online calculator. The predictive accuracy of the model was good to very good as the C-statistics to predict 5-year OS was 0.696 in the training dataset and 0.672 with bootstrapping resamples (n = 5000) in the test dataset. Conclusion: A novel, online calculator was developed to estimate the 5-year survival probability for patients undergoing resection for ICC. This tool could help provide useful information to guide treatment decision-making and inform conversations about prognosis.
- Cardiac Rehabilitation Availability and Density Around the GlobePublication . Turk-Adawi, K; Supervia, M; Lopez-Jimenez, F; Pesah, E; Ding, R; Britto, RR; Bjarnason-Wehrens, B; Derman, W; Abreu, A; Babu, AS; Santos, CA; Jong, SK; Cuenza, L; Yeo, TJ; Scantlebury, D; Andersen, K; Gonzalez, G; Giga, V; Vulic, Du; Vataman, E; Cliff, J; Kouidi, E; Yagci, I; Kim, C; Benaim, B; Estany, ER; Fernandez, R; Radi, B; Gaita, D; Simon, A; Chen, SY; Roxburgh, B; Martin, JC; Maskhulia, L; Burdiat, G; Salmon, R; Lomelí, H; Sadeghi, M; Sovova, E; Hautala, A; Tamuleviciute-Prasciene, E; Ambrosetti, M; Neubeck, L; Asher, E; Kemps, H; Eysymontt, Z; Farsky, S; Hayward, J; Prescott, E; Dawkes, S; Santibanez, C; Zeballos, C; Pavy, B; Kiessling, A; Sarrafzadegan, N; Baer, C; Thomas, R; Hu, D; Grace, SLBackground: Despite the epidemic of cardiovascular disease and the benefits of cardiac rehabilitation (CR), availability is known to be insufficient, although this is not quantified. This study ascertained CR availability, volumes and its drivers, and density. Methods: A survey was administered to CR programs globally. Cardiac associations and local champions facilitated program identification. Factors associated with volumes were assessed using generalized linear mixed models, and compared by World Health Organization region. Density (i.e. annual ischemic heart disease [IHD] incidence estimate from Global Burden of Disease study divided by national CR capacity) was computed. Findings: CR was available in 111/203 (54.7%) countries; data were collected in 93 (83.8% country response; N = 1082 surveys, 32.1% program response rate). Availability by region ranged from 80.7% of countries in Europe, to 17.0% in Africa (p < .001). There were 5753 programs globally that could serve 1,655,083 patients/year, despite an estimated 20,279,651 incident IHD cases globally/year. Volume was significantly greater where patients were systematically referred (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.35-1.38) and programs offered alternative models (OR = 1.05, 95%CI = 1.04-1.06), and significantly lower with private (OR = .92, 95%CI = .91-.93) or public (OR = .83, 95%CI = .82-84) funding compared to hybrid sources.Median capacity (i.e., number of patients a program could serve annually) was 246/program (Q25-Q75 = 150-390). The absolute density was one CR spot per 11 IHD cases in countries with CR, and 12 globally. Interpretation: CR is available in only half of countries globally. Where offered, capacity is grossly insufficient, such that most patients will not derive the benefits associated with participation.
- Standardized Assessment of the Signal Intensity Increase on Unenhanced T1-Weighted Images in the Brain: the European Gadolinium Retention Evaluation Consortium (GREC) Task Force Position StatementPublication . Quattrocchi, CC; Ramalho, J; van der Molen, AJ; Rovira, À; Radbruch, AAfter the initial report in 2014 on T1-weighted (T1w) hyperintensity of deep brain nuclei following serial injections of linear gadolinium-based contrast agents (GBCAs), a multitude of studies on the potential of the marketed GBCAs to cause T1w hyperintensity in the brain have been published. The vast majority of these studies found a signal intensity (SI) increase for linear GBCAs in the brain-first and foremost in the dentate nucleus-while no SI increase was found for macrocyclic GBCAs. However, the scientific debate about this finding is kept alive by the fact that SI differences do not unequivocally represent the amount of gadolinium retained. Since the study design of the SI measurement in various brain structures is relatively simple, MRI studies investigating gadolinium-dependent T1w hyperintensity are currently conducted at multiple institutions worldwide. However, methodological mistakes may result in flawed conclusions. In this position statement, we assess the methodological basis of the published retrospective studies and define quality standards for future studies to give guidance to the scientific community and to help identify studies with potentially flawed methodology and misleading results. KEY POINTS: • A multitude of studies has been published on the potential of the marketed GBCAs to cause T1w hyperintensity in the brain. • The gadolinium-dependent T1w hyperintensity in the brain depends on patient's history, types of GBCAs used (i.e., linear vs. macrocyclic GBCAs) and MR imaging setup and protocols. • Quality standards for the design of future studies are needed to standardize methodology and avoid potentially misleading results from retrospective studies.
- Análise da Revisão Cochrane: Reabilitação Cardíaca Baseada no Exercício na Doença Arterial Coronária. Cochrane Database Syst Rev. 2016;1:CD001800Publication . Carvalheira-dos-Santos, R; Delgado, RM; Ferreira-dos-Santos, G; Vaz-Carneiro, AA doença coronária, responsável por um terço de todas as mortes, é a causa de morte mais comum em todo o mundo. Todavia, com o decréscimo das taxas de mortalidade associadas a esta patologia, observa-se um número crescente de doentes com a doença, com aumento da necessidade de gestão dos seus sintomas e prognóstico. A reabilitação cardíaca, componente essencial do tratamento contemporâneo da doença arterial coronária, é uma intervenção complexa que envolve variadas técnicas, incluindo exercício físico, correção dos fatores de risco cardiovasculares tradicionais, terapia comportamental e apoio psicológico, sendo considerada uma prioridade em países em que a prevalência da doença é elevada. Esta revisão sistemática Cochrane constitui uma atualização de uma revisão Cochrane publicada em 2011, tendo identificado 16 novos ensaios clínicos (3872 doentes), predominantemente em status pós-enfarte agudo do miocárdio e pós-cirurgia de revascularização miocárdica. Incluiu, assim, 63 ensaios clínicos aleatorizados que estudaram a eficácia e o custo-efetividade da reabilitação cardíaca baseada no exercício físico, em pacientes com doença arterial coronária. A confiança na evidência científica variou de baixa a moderada. Dos principais resultados destaca-se o efeito da reabilitação cardíaca, em comparação com a ausência de exercício físico, na redução na mortalidade cardiovascular, todavia sem redução da mortalidade total. Apesar da reabilitação cardíaca ter diminuído o risco global de internamento hospitalar, o mesmo não se verificou para o risco de enfarte, cirurgia de revascularização miocárdica ou intervenção coronária percutânea. Neste artigo sumarizam-se e discutem-se os principais resultados, conclusões e implicações desta revisão sistemática para a prática clínica.