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Background Physical activity is associated with reduced arterial stiffness, although such a relationship has not been reported in those with resistant hypertension. Therefore, this study aimed to determine the association between daily physical activity and arterial stiffness in patients with resistant hypertension. Methods Fifty-seven (57) patients with resistant hypertension (50.9% men), aged 58.8±9.4 years, were consecutively recruited. Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). Daily physical activity was objectively assessed with accelerometers during 7 consecutive days. Results Patients had a body mass index of 29.0±4.0 kg/m2 (84.3% overweight/obese) and were taking an average 4.5 antihypertensive medications. Overall, the cf-PWV was 9.2±2.4 m/s and the majority of participants (n=41, 71.9%) presented a cf-PWV Conclusions Higher daily levels of light-intensity and total physical activity were associated with lower arterial stiffness. Nonetheless, this association is weak and attenuated or abolished when adjusted for blood pressure and age. These results suggest that physical activity may play an important role as a lifestyle intervention for patients with resistant hypertension. Future studies with larger samples sizes are necessary to confirm this preliminary data.

Mesalazine is a widely prescribed drug, used for the treatment of ulcerative colitis to both induce and maintain remissions in disease. Mesalazine therapy has been associated with a low rate of serum enzyme elevations and a with rare instances of clinically apparent acute liver injury.A 51-year-old Caucasian woman with ulcerative colitis was treated with mesalazine. Two weeks later, the patient presented severe liver cholestatic injury. No symptoms of generalized hypersensitivity were seen. She had no history of liver disease and was known to have normal routine liver tests before starting treatment. The liver biopsy revealed mild periportal necroinflammatory lesions with no fibrosis, suggestive of drug-induced liver injury. The patient's symptoms were resolved by discontinuing the mesalazine treatment; within 6 months, all her liver panels returned to normal. After extensively excluding other potential causes of liver injury and with clinical and lab resolution after discontinuing the drug, we assumed mesalazine as the cause of hepatic toxicity.We describe a patient with ulcerative colitis who developed severe but fully reversible liver cholestatic injury following the prescription of mesalazine. This case reinforces the possibility of a causal relationship between mesalazine therapy and toxic hepatic injury without systemic hypersensitivity. Although it is a usually well-tolerated drug, clinicians should be alert and discontinue therapy when liver dysfunction occurs to avoid the development of chronic hepatitis and liver fibrosis.

Crohn disease (CD) and ulcerative colitis (UC) are considered chronic disorders of the gastrointestinal tract, lifelong medication often being necessary. Furthermore, they have significant implications on the quality of life. In the past few years, major advances have been achieved concerning the treatment of inflammatory bowel disease. These advances are expanding the possibilities for managing these patients. Janus kinase (JAK) inhibitors represent the most auspicious treatment to date because they consist of drugs that are orally administered, with a short half-life and low antigenicity. In addition, they seem to concurrently lessen various proinflammatory routes. In fact, tofacitinib has already been approved in patients with UC, both naïve and with prior exposure to tumor necrosis factor inhibitors. In CD, the results with tofacitinib have been less impressive. Several other JAK inhibitors are currently being investigated. However, given the wide spectrum of immunosuppressive effects, special attention has been given to the safety profile of these drugs, namely with regard to the occurrence of thromboembolic events, opportunistic infections, and malignancy. In this article, we review key evidence on the efficacy and safety of JAK inhibitors concerning both UC and CD.

Reports suggest that the blood pressure (BP) response to an acute bout of exercise is associated with the BP response to aerobic training in participants with elevated BP. These associations have not been tested among patients with resistant hypertension. This study aimed to determine whether the BP response to acute exercise predicts the 24-h ambulatory BP response to a 12-week exercise training program in patients with resistant hypertension (n = 26, aged 59.3 ± 8.2 years, 24-h ambulatory BP 127.4 ± 12.2/75.6 ± 7.8 mm Hg) who completed the exercise arm of the EnRicH trial. Ambulatory BP measurements were obtained before and after the exercise program to assess the chronic BP response. To assess acute BP changes, resting BP was measured before and 10 min after three exercise sessions in the third week of training and averaged. The resting systolic (9.4 ± 6.7, p 0.001) and diastolic BP (1.9 ± 3.2, p = 0.005) were reduced after acute exercise. The 24-h systolic (6.2 ± 12.2, p = 0.015) and diastolic BP (4.4 ± 6.1, p = 0.001) were decreased after exercise training. The reductions in systolic BP after acute exercise were associated with the reductions in 24-h systolic BP after exercise training (ß = 0.538, adjusted r

The clinical implications of the biopsy findings in cases of drug-induced liver injury (DILI) are not fully elucidated. The aim of this study was to evaluate the histopathological findings of cases diagnosed as DILI and to correlate them with clinical and biochemical findings (such as causality assessment algorithms). We searched our department database for all cases of liver biopsy with findings consistent with toxic liver disease and selected those with a clinical diagnosis of DILI. The causative relationships were established according to Roussel Uclaf Causality Assessment Method (RUCAM). A total of 53 cases of DILI were reviewed, most of them diagnosed in hospitalized patients (83%). The analytical toxicity profile was hepatocellular (R > 5) in 60% of the cases and cholestatic (R

Summary Background & Aims Inflammatory bowel diseases (IBD) are associated with various hepatobiliary disorders. There is a strong association for primary sclerosing cholangitis (PSC). Primary biliary cholangitis (PBC), another autoimmune cholestatic liver disease, is not usually associated with IBD. The aim of this study is to report cases of PBC-associated IBD, their clinical features, response to therapy, and long-term outcome. Methods Retrospective analysis of a prospectively collated database identified patients presenting with PBC-associated IBD from 2006 to 2016. PBC has been diagnosed according to accepted criteria, and staged according to Ludwig classification. A magnetic resonance cholangiopancreatography (MRCP) was performed to rule out PSC. Response to ursodeoxycholic acid (UDCA) therapy has been assessed by using the Paris II criteria. Results A total of six patients (five females) with PBC-associated IBD were identified. Median age at IBD diagnosis was 44.7 years (range 22.5–48.8). Three had Crohn's disease and three ulcerative colitis. PBC was diagnosed in all after IBD had been diagnosed. All patients presented with cholestasis, all were positive for anti-mitochondrial antibodies. MRCP was normal in all. Liver biopsy was consistent with PBC (stage I in one, stage II in five). One year after initiation of UDCA, all patients responded to therapy. Conclusion Herein we describe the largest series reported to date of PBC-associated IBD. Although the coexistence of the two conditions is rare, PBC should be considered during the work-up of abnormal liver function tests in patients with IBD.

The therapeutic potential of exercise training in the mobilization of endothelial progenitor cells (EPCs) into the peripheral blood in patients with cardiovascular disease is not yet clear. A systematic review and meta-analysis was performed in order to assess the effectiveness of exercise training in increasing the number of circulating EPCs in patients with cardiovascular disease. A literature search was conducted across the PubMed, Scopus, Web of Science and EBSCO databases, including the reference lists of relevant papers. The quality of randomized clinical trials was evaluated using the PEDro scale. The primary outcome data were circulating EPC levels. Six studies (236 participants) – three on heart failure (n=111), one on peripheral arterial disease (n=40) and two on coronary artery disease (n=85) – were included. There was an increase in EPC levels in the exercise training groups (effect size [ES]=0.57; 95% CI: 0.01-1.12), with considerable heterogeneity (I2=75.6%; p

Background Augmented arterial stiffness and reduced cardiorespiratory fitness are associated with increased morbidity and mortality from coronary artery disease (CAD). The relationship between exercise capacity and arterial stiffness is independent of known influencing variables in CAD. This study aimed to analyse the interaction between exercise capacity, arterial stiffness and early vascular ageing in patients with CAD. Methods This cross-sectional study included 96 CAD patients with myocardial infarction (55.9 ± 10.9 years, 81 men) referred to cardiac rehabilitation. Arterial stiffness was assessed using carotid-femoral pulse wave velocity (cf-PWV). Cardiopulmonary exercise test was performed to measure VO2peak. Comparisons of VO2peak across cf-PWV risk threshold values (high-risk cf-PWV ≥ 10 m/s) and tertile groups, and across cf-PWV threshold values and age groups (younger group Results Patients with high-risk cf-PWV had lower VO2peak than those with low-risk cf-PWV (p Conclusions Arterial stiffening is associated with lower cardiorespiratory fitness in CAD patients with myocardial infarction. When its values are above risk threshold, exercise capacity is impaired regardless of the relationship between age and arterial stiffness.

Introduction Resistant Hypertension (RH) defined by Ambulatory blood pressure monitoring (ABPM) isn't so common. Prognostic CV by ABPM of RH is uncertain. Objective RH Population defined by ABPM, followed 5.9±5.0 years and prognostic value of ABPM for new CV events (CVe). Design and method ABPM-collected 1999–2019. Identified RH patients by ABPM. Obtained anthropometric, clinic, laboratorial data from the patient and clinical records. CVe defined by: stroke (ST) (Ischemic (STisq), haemorrhagic (SThs)), Coronary Event (CD), Other CV events (OCV) (acute heart failure (HF), peripheral arterial disease (PAD). Follow-up finished with event, last evaluation of the patient or death. Results 258 patients, follow-up – 5.9±5.0 years,158 males, mean age – 60.4±11 years. Diabetes Mellitus (DM) 45.3%, Dyslipidaemia 74.4%, Obesity 45.3%, Chronic Kidney Disease 37.2%, previous CVe (PCVe) 34.5%. Observed 68 CVe: 26 ST (21 STisq, 5 SThs), 21 CD, 21 OCV (15 HF, 6 PAD). 18 death (8 unknown, 1 infection, 2 cancer, 1 sudden death, 2 STisq, 1 CD, 3 HF). When compared those with event vs no-event (fig. 1), in T student to independent samples, those with event had larger left atrium (42.6±5.7 vs 40.2±4.7, p Conclusion In our sample of RH the definition by ABPM is essential. PP is the key prognosis for future CVe, special if analysed by the cut of PP-60 mmHg. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier survival curves

Since the beginning of the pandemic, patients with inflammatory bowel diseases (IBD) have been considered at high-risk for infection and complications of COVID-19. However, IBD patients and patients taking immunosuppressive therapy were excluded from clinical phase III vaccine trials, complicating the assessment of effectiveness of these new vaccines. From past experience we know that adapted vaccination strategies may be appropriate in some IBD patients to optimize immunogenicity. We review current evidence on SARS-CoV-2 vaccination relevant to IBD patients, including immune responses from humoral to cellular, emerging data on new variants and off-label vaccination schemes. We also identify clinical and scientific knowledge gaps that can be translated into both large-scale population-based studies and targeted vaccine studies to describe the precise immune responses induced by SARS-CoV-2 vaccines in IBD patients. We strongly endorse the recommendation of vaccinating IBD patients to ensure maximal protection from COVID-19 both for the individual and the community.

Introduction Resistant hypertension is a major challenge of modern cardiovascular medicine, as it is a puzzling problem without a clear solution. Exercise training clearly reduces blood pressure (BP) and oxidative stress in patients with hypertension, however evidence is limited regarding resistant hypertension. Purpose To determine the effect of an aerobic exercise training program in BP, angiotensin II and oxidative stress in patients with resistant hypertension. Methods EnRicH is a prospective, two-center, single-blinded, randomized controlled trial with a parallel two-arm group. Sixty patients with resistant hypertension were randomly assigned in a 1:1 ratio to undergo a 12-week aerobic exercise training program (exercise) or usual care (control). The powered primary efficacy measure was 24-hour ambulatory systolic BP change from baseline. Secondary outcome measures included daytime and nighttime ambulatory BP, office BP, cardiorespiratory fitness, and oxidative stress and inflammatory biomarkers: Interferon-gamma (IFN-y), Angiotensin II, vascular endothelial growth factor (VEGF), and superoxide dismutase (SOD). Results Fifty-three patients (exercise n=26, control n=27) completed the study. Patients were mainly women (54.7%), with an office BP of 140.7±15.9/84.2±9.4 mm Hg and taking an average of 4.6 antihypertensive medications (median, 5; range, 3 to 7). At baseline, no differences were found between groups for the study outcomes and patient characteristics. Ambulatory systolic BP was reduced −7.1 mm Hg (95% CI, −12.8 to −1.4; P=0.015) in the exercise group (127.4±12.2 to 121.2±12.2, p=0.007) compared to control group (126.1±17.2 to 126.9±15.2, p=514) over 24-hour. In addition, 24-hour ambulatory diastolic BP (−5.1 mm Hg, −7.9 to −2.3, P=0.001), daytime ambulatory systolic (−8.4 mm Hg, −14.3 to −2.5, P=0.006), and diastolic BP (−5.7 mm Hg, −9.0 to −2.4, P=0.001) were also reduced in the exercise group compared to the control group. There were no differences in the change of nighttime ambulatory BP between groups. Cardiorespiratory fitness improved in the exercise group by 14% (4.7 ml.kg-1.min-1, P Conclusions A 12-week moderate intensity aerobic exercise program reduced ambulatory BP, angiotensin II and oxidative stress in patients with resistant hypertension. The antihypertensive effects of exercise in patients with resistant hypertension may be mediated by positive changes in oxidative stress and inflammatory biomarkers. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): European Union through European Regional Development Fund – Operational Competitiveness Factors Program (COMPETE)Portuguese Government through FCT - Foundation for Science and Technology

BACKGROUND AND AIMS Pancreatic ductal adenocarcinoma (PDAC) diagnosis can be difficult in a chronic pancreatitis (CP) background, especially in its mass forming presentation. We aimed to assess the accuracy of glypican-1-positive circulating exosomes (GPC1+crExos) to distinguish PDAC from CP versus the state-of-the-art CA 19-9 biomarker. METHODS This was a unicentric prospective cohort. Endoscopic ultrasound with fine-needle aspiration or biopsy and blood tests (GPC1+crExos and serum CA 19-9) were performed. RESULTS The cohort comprised 60 PDAC and 29 CP (7 of which mass forming - MF) patients. Median levels of GPC1+crExos were significantly higher in PDAC (99.7%) versus CP (28.4%; p

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Portuguese Foundation for Science and Technology (FCT) European Regional Development Fund – Operational Competitiveness Factors Program (COMPETE) Background Physical activity has been associated with reduced arterial stiffness in patients with hypertension. However, in resistant hypertension, a specific population with an increased risk for target organ damage, cardiovascular morbidity, and mortality, the evidence is sparse. Purpose The present study aimed to determine the association between daily physical activity and arterial stiffness in patients with resistant hypertension. Methods Fifty-seven patients with resistant hypertension were recruited. Physical activity was objectively assessed during 7 consecutive days with accelerometers. Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV) . Results Participants (50.9% men), aged 58.8 ± 9.4 years, were mainly overweight and were taking in average 4.5 antihypertensive medications. The cf-PWV showed an inverse correlation with light-intensity physical activity (r = -0.290, p = 0.029) and total daily physical activity (r = -0.287, p = 0.030). Additionally, cf-PWV tended to be inversely associated with the number of steps per day (r = -0.242, p = 0.069). Patients with higher risk of cardiovascular events (cf-PWV ≥ 10 m/s) tended to spend less time in light-intensity physical activity (324.0 ± 129.4 vs. 380.5 ± 103.1 min/day, p = 0.090) and to perform less total daily physical activity (351.5 ± 141.7 vs. 411.7 ± 109.1 min/day, p = 0.091) than participants with cf-PWV below the risk threshold value. Conclusions Higher levels of total physical activity and daily levels of light-intensity were associated to lower arterial stiffness. These results emphasize the importance of physical activity as a nonpharmacological tool for patients with resistant hypertension.

Crohn’s disease (CD) is a complex disorder with variable age of onset, disease location and behavior. It is characterized by a transmural inflammation that may involve any portion of the gastrointestinal tract. Ileocolonoscopy with biopsy is established as the first-line investigation for suspected CD. However, small bowel involvement is more difficult to assess by conventional endoscopy. Therefore, radiological imaging should also be performed to complement ileocolonoscopy in all patients with suspected CD. Recently, video capsule endoscopy and device-assisted enteroscopy have revolutionized the management of small bowel CD. In fact, video capsule endoscopy is a non-invasive test that provides the visualization of the entire small bowel mucosa, which can assist in the diagnosis of CD and assess the therapeutic response. On the other hand, device-assisted enteroscopy enables direct tissue sampling for histopathology confirmation when traditional endoscopy, video capsule endoscopy and cross-sectional imaging are inconclusive. Moreover, it allows therapeutic interventions such as balloon stricture dilation. In this chapter, we review the role of endoscopy in the diagnosis and management of patients with small bowel CD.

Background The current standard of treatment in primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), although a considerable proportion of patients show incomplete response resulting in disease progression. Objective This study aimed to assess the prevalence of incomplete response to UDCA and determine associated patients' characteristics. Methods Patients with PBC as main diagnosis were included from a national multicentric patient registry—Liver.pt. Main endpoints included incomplete response to UDCA treatment according to Barcelona, Paris I and Paris II criteria, Globe and UK PBC scores and the association between baseline characteristics and incomplete response according to Paris II criteria. Results A total of 434 PBC patients were identified, with a mean age of 55 years and 89.2% females. Nearly half of patients were asymptomatic at diagnosis and 93.2% had positive anti‐mitochondrial antibodies. Almost all patients (95.6%) had been prescribed at least one drug for PBC treatment. At the last follow‐up visit, 93.3% were under treatment of which 99.8% received UDCA. Incomplete response to UDCA was observed in 30.7%, 35.3%, 53.7% and 36.4% of patients according to Barcelona, Paris I, Paris II criteria and Globe score, respectively. After adjusting for age and sex, and accordingly to Paris II criteria, the risk for incomplete biochemical response was 25% higher for patients with cirrhosis at diagnosis (odds ratio [OR] = 1.25; 95% confidence interval [95%CI]: 1.02–1.54; p = 0.033) and 35% (95%CI:1.06–1.72; p = 0.016) and 5% (OR = 1.05; 95%CI:1.01–1.10; p = 0.013) for those with elevated gamma‐glutamyl transferase (GGT) and alkaline phosphatase (ALP). Conclusion A considerable proportion of patients showed incomplete biochemical response to UDCA treatment according to Paris II criteria. Cirrhosis, elevated GGT and ALP at diagnosis were identified as associated risk factors for incomplete response. Early identification of patients at risk of incomplete response could improve treatment care and guide clinical decision to a more careful patient monitorization., Key summary Summarise the established knowledge on this subject Primary biliary cholangitis is a liver disease that can progress to end‐stage liver disease, with premature death or need for liver transplantation.Treatment with ursodeoxycholic acid (UDCA) significantly increases liver transplant‐free survival. However, incomplete response to UDCA reduces this beneficial effect. What are the significant and/or new findings of this study? By evaluating prevalence and risk factors for UDCA incomplete response through a large multicentric national registry it was found that 53.7% of patients were incomplete responders, according to Paris II criteria, with cirrhosis, elevated gamma‐glutamyl transferase and alkaline phosphatase at diagnosis as the main risk factors.These findings suggest that patients diagnosed at an advanced stage should be closely monitored and might benefit from novel therapies to improve outcomes if incomplete response is present.

Background & Aims In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid. Methods We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs. Results Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P 2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158–3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139–3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269–4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 μg/g. Conclusions We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy.

Summary Background Most patients with autoimmune hepatitis (AIH) respond to a combination of prednisolone and azathioprine. For patients who are intolerant or refractory to azathioprine, proposed alternative therapies are based on scarce data, limited to transplant centres and with short-term follow-up periods. Objective To evaluate the long-term efficacy and safety of MMF as a second-line therapy in patients with AIH managed at a tertiary non-transplant centre. Methods Retrospective analysis of a prospectively collated database identified AIH patients who received MMF from 2006 to 2015. Clinical, biochemical and immunological parameters were assessed at 3-, 6- and 12-months, and at last follow-up. Biochemical response (BR) was defined as improvement of transaminases, complete remission (CR) as normalisation of transaminases and IgG, while others were considered non-responders (NR). Results Eighteen out of 151 (12%) AIH patients received MMF. Nine received MMF due to azathioprine-intolerance (group 1), while nine due to refractory disease (group 2). In group 1, CR and BR was achieved in six (67%) and two (22%) patients respectively. In group 2, CR and BR was achieved in one (11%) and five (56%) patients respectively. Adverse events occurred in eight patients (44%), with one patient requiring drug discontinuation. After a medium follow-up of 78 (31–116) months, there was a significant decrease in transaminase levels, mirrored by decrease in prednisolone dose from 25 to 6.25 mg/day (P Conclusion Long-term therapy with MMF is safe and effective in AIH patients requiring second-line therapies, and these patients can be effectively managed at tertiary non-liver transplant centres.

Background: videocapsule endoscopy (VCE) is currently the most sensitive diagnostic tool to detect early small bowel inflammation. A Lewis score (LS) of ≥ 135 as the cutoff value for the presence of significant inflammatory activity in patients undergoing VCE for suspected Crohn’s disease (CD) has been suggested as a useful tool for the diagnosis of CD. The aim of this study was to evaluate the diagnostic and prognostic accuracy of the LS in patients with suspected CD undergoing VCE. Methods: a retrospective single-center study was performed that included patients who underwent VCE for suspected CD between January 2010 and December 2015. Inflammatory activity was assessed with the LS. Patients were grouped according to the criteria of the International Conference on Capsule Endoscopy (ICCE) for the definition of suspected CD; group 1: patients not fulfilling ICCE and group 2: patients with ≥ 2 ICCE criteria. Results: one hundred and ninety-one patients were included, 61% were female and the mean age was 39 ± 14 years. VCE detected significant inflammatory activity (LS ≥ 135) in 81 patients (42%); 24 patients from group 1 (32%) and 57 patients from group 2 (50%) (p = 0.014). During a mean follow-up period of 41 ± 21 months (12-79), a CD diagnosis was determined in 60 patients (31%); 55 patients with LS ≥ 135 (92%) and five patients with LS < 135 (5%) (p < 0.001). The LS showed a good diagnostic accuracy with an AUROC of 0.93 (p < 0.001). During the first year after diagnosis, there was a significant association between a higher LS and the need for immunomodulatory therapy, biological therapy, bowel resection surgery or hospital admission due to a CD flare-up. Conclusions: the LS (cutoff ≥ 135) is very useful in the diagnosis of CD in patients undergoing VCE. Moreover, higher values of this score was associated with prognostic variables.

Although there has been an observed progress in the treatment of hypertension, its prevalence remains elevated and constitutes a leading cause of cardiovascular disease development. Resistant hypertension is a challenge for clinicians, as the available treatment options have reduced success. Physical activity and exercise training play an important role in the management of blood pressure. The importance of physical activity and exercise training as part of a comprehensive lifestyle intervention is acknowledged by several professional organizations in their recommendations/guidelines for the management of arterial hypertension. Aerobic exercise, dynamic resistance exercise, and concurrent training - the combination of dynamic resistance and aerobic exercise training in the same exercise session or on separate days - has been demonstrated to reduce blood pressure and help in the management of hypertension. The present review draws attention to the importance of exercise training in the management of blood pressure in both hypertension and resistant hypertension individuals. This work is financed by FEDER funds through the Operational Competitiveness Factors Program – COMPETE and by National Funds through FCT – Foundation for Science and Technology within the project “P2020-PTDC/DTPDES/1725/2014.” iBiMED is a research unit supported by the Portuguese Foundation for Science and Technology (FCT) (Ref: UID/BIM/04501/2013) and POCI-01–0145-FEDER-007628 funds. CIDESD is a research unit supported by FCT (UID/DTP/04045/2013) and by the European Regional Development Fund, through COMPETE 2020 (POCI-01–0145-FEDER-006969). Susana Lopes received a PhD grant from the Foundation for Science and Technology (SFRH/BD/129454/2017). published

Background and Aims Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters. Methods This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naïve to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6. Results A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 μg/mL vs 1.3 μg/mL, p = 0.0013; and 3.1 μg/mL vs 1.7 μg/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 μg/mL vs 1.7 μg/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044]. Conclusions A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6.

The broader use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) has been associated with a high rate of adverse reactions. Dermatological complications are among the most common adverse events. We assessed the incidence, risk factors, management, and outcome of anti-TNF-induced dermatological complications in a large cohort of IBD patients. This was an observational retrospective study at a single tertiary referral center. All consecutive adult IBD patients treated with anti-TNF agents between 2005 and 2015 were identified. Patients who developed at least one dermatological complication while on anti-TNF therapy were included. From the 732 patients treated with anti-TNF agents, 211 (29%) developed at least one dermatological complication: 52% women (mean age of 42 ± 13 years), 85% with Crohn’s disease, 67% were under infliximab. Median follow-up time under anti-TNF therapy was 53 (27–77) months. Dermatological complications recorded were: infections (13.5%), psoriasiform lesions (5.3%), injection/infusion reactions (3.8%), skin cancer (0.5%), and miscellaneous (5.6%). Overall, female gender (OR = 1.658, p = 0.029), smoking (OR = 2.021, p = 0.003), and treatment with an infliximab dose of 10 mg/kg (OR = 2.012, p = 0.007) were independent risk factors for dermatological complications in multivariable analysis. Female gender (OR = 3.63, p = 0.017), smoking (OR = 2.846, p = 0.041), and treatment with adalimumab (OR = 8.894, p

IMPORTANCE: Limited evidence suggests exercise reduces blood pressure (BP) in individuals with resistant hypertension, a clinical population with low responsiveness to drug therapy. OBJECTIVE: To determine whether an aerobic exercise training intervention reduces ambulatory BP among patients with resistant hypertension. DESIGN, SETTINGS, AND PARTICIPANTS: The Exercise Training in the Treatment of Resistant Hypertension (EnRicH) trial is a prospective, 2-center, single-blinded randomized clinical trial performed at 2 hospital centers in Portugal from March 2017 to December 2019. A total of 60 patients with a diagnosis of resistant hypertension aged 40 to 75 years were prospectively enrolled and observed at the hospitals’ hypertension outpatient clinic. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to a 12-week moderate-intensity aerobic exercise training program (exercise group) or a usual care control group. The exercise group performed three 40-minute supervised sessions per week in addition to usual care. MAIN OUTCOMES AND MEASURES: The powered primary efficacy measure was 24-hour ambulatory systolic BP change from baseline. Secondary outcomes included daytime and nighttime ambulatory BP, office BP, and cardiorespiratory fitness. RESULTS: A total of 53 patients completed the study, including 26 in the exercise group and 27 in the control group. Of these, 24 (45%) were women, and the mean (SD) age was 60.1 (8.7) years. Compared with the control group, among those in the exercise group, 24-hour ambulatory systolic BP was reduced by 7.1 mm Hg (95% CI, −12.8 to −1.4; P = .02). Additionally, 24-hour ambulatory diastolic BP (−5.1 mm Hg; 95% CI, −7.9 to −2.3; P = .001), daytime systolic BP (−8.4 mm Hg; 95% CI, −14.3 to −2.5; P = .006), and daytime diastolic BP (−5.7 mm Hg; 95% CI, −9.0 to −2.4; P = .001) were reduced in the exercise group compared with the control group. Office systolic BP (−10.0 mm Hg; 95% CI, −17.6 to −2.5; P = .01) and cardiorespiratory fitness (5.05 mL/kg per minute of oxygen consumption; 95% CI, 3.5 to 6.6; P

AIM To evaluate the accuracy and best cut-off value of fecal calprotectin (FC) and fecal lactoferrin (FL) to predict disease recurrence in asymptomatic patients presenting with anastomotic strictures. METHODS This was a longitudinal single tertiary center study based on prospectively collected data (recorded in a clinical database created for this purpose) performed between March 2010 and November 2014. Crohn’s disease (CD) patients with anastomotic stricture who submitted to postoperative endoscopic evaluation were included. Stools were collected on the day before bowel cleaning for FC and FL. Endoscopic balloon dilation (EBD) was performed if the patient presented an anastomotic stricture not traversed by the colonoscope, regardless of patients’ symptoms. Successful dilation was defined as passage of the colonoscope through the dilated stricture into the neotermimal ileum. Postoperative recurrence was defined as a modified Rutgeerts score of ≥ i2b. RESULTS In a total of 178 patients who underwent colonoscopy, 58 presented an anastomotic stricture, 86% were asymptomatic, and 48 (54% male; median age of 46.5 years) were successfully dilated. Immediate success rate was 92% and no complications were recorded. FC and FL levels correlated significantly with endoscopic recurrence (P < 0.001) with an optimal cut-off value of 90.85 µg/g (sensitivity of 95.5%, specificity of 69.2%, positive predictive value (PPV) of 72.4%, negative predictive value (NPV) of 94.7% and accuracy of 81%] for FC and of 5.6 µg/g (sensitivity of 77.3%, specificity of 69.2%, PPV of 68%, NPV of 78.4% and accuracy of 72.9%) for FL. CONCLUSION Fecal markers are good predictors of CD endoscopic recurrence in patients with asymptomatic anastomotic stricture. FC and FL may guide the need for EBD in this context.

Aims: The Xeltis aortic valve leaflets are made from a bioabsorbable supramolecular polymer that guides the tissue to restoring itself. It is mounted on a self-expanding nitinol frame that includes three feelers and a native leaflet clipping mechanism. We sought to investigate the acute valve performance in a preclinical setting. Methods and results: In 33 sheep, 26 mm Xeltis aortic valves were transapically implanted in a 23 mm native annulus. Aortography (analysable, n = 28) and echocardiography (analysable, n = 20) images were acquired immediately after implantation of the Xeltis aortic valve to assess the acute device performance. On echocardiography, transvalvular peak pressure gradient (PG) was 7.4 (IQR: 6.0-8.9) mmHg, mean PG was 4.0 (IQR: 3.0-5.0) mmHg, and effective orifice area was 2.2 (IQR: 1.6-2.5) cm(2). Trace (n = 6), mild (n = 2) and no (n = 12) transvalvular aortic regurgitation (AR) were seen. Likewise, no paravalvular AR was detected in 7 cases, whereas trace, mild and moderate were seen in 7, 5 and 1 cases, respectively. On quantitative videodensitometric AR (VD-AR) assessment, a median value of 6% (IQR: 1-12%) of AR was seen. Three cases had a VD-AR superior to 17%, which has a prognostic significance. Out of these three cases, two had echocardiographic assessment available, which showed mild and moderate paravalvular regurgitation due to inadequate leaflet clipping. Conclusions: In a transapical ovine model, the novel restorative transcatheter aortic valve with bioabsorbable leaflets demonstrated good haemodynamic performance comparable to commercially available devices. The highly porous polymeric leaflets demonstrated good competence immediately after implantation with no cases having > mild transvalvular AR

Background: Cholangiocarcinoma is the second most frequent primitive liver malignancy and is responsible for 3% of the malignant gastrointestinal neoplasms. The aims of this study were to determine the association of serum levels of CA 19-9 at diagnosis with other clinical data and serum liver function tests and to identify possible factors that influence the survival rates during follow-up. Methods: Retrospective observational study of 89 patients with a diagnosis of cholangiocarcinoma followed at the Department of Gastroenterology during 5 years. Statistical analyses were performed using SPSS version 20.0. Results: Patients were followed up for a median time of 127 days (IQR: 48-564), and the median age at diagnosis was 71.0 years (IQR: 62.0-77.5). The median survival rate was 14.0 months (IQR: 4.3-23.7), and the mortality rate was 79%. Patients with CA 19-9 levels ≥ 103 U/L had lower albumin levels and higher levels of alanine aminotransferase and γ-glutamyltransferase. CA 19-9 levels ≥ 103 U/L were associated with a higher probability of metastization ( p = 0.001) and lower rates of treatment with curative intent ( p = 0.024). In a multivariate analysis, CA 19-9 levels

Background and Aims The histological status of ulcerative colitis [UC] patients in clinical and endoscopic remission has gained space as an important prognostic marker and a key component of disease monitoring. Our main aims were to compare two histological indexes—the continuous Geboes score [GS] and the Robarts Histopathology index [RHI]—regarding their definitions of histological remission and response, and the ability of faecal calprotectin [FC] levels to discriminate between these statuses. Methods This was an analysis of three prospective cohorts including 422 patients previously enrolled in other studies. Results The two continuous scores [GS and RHI] were shown to be significantly correlated [correlation coefficient of 0.806, p < 0.001] and particularly close regarding their definition of histological response: 95% and 88% of all patients classified as having/not having [respectively] histological response according to RHI also did so according to GS. Moreover, median FC levels in patients with histological response were lower than those in patients without histological response [GS: 73.00 vs 525.00, p < 0.001; RHI: 73.50 vs 510.00, p < 0.001]; a similar trend was observed when FC levels of patients in histological remission were compared to those of patients with histological activity [GS: 76.00 vs 228.00, p < 0.001; RHI: 73.50 vs 467.00, p < 0.001]. FC levels allowed us to exclude the absence of histological remission [according to RHI] and absence of histological response [according to RHI and GS], with negative predictive values varying from 82% to 96%. However, optimization of the FC cut-off to exclude the absence of histological remission, as for the continuous GS, falls within values that resemble those of the healthy population. Conclusion The continuous GS and RHI histological scores are strongly correlated in their definitions of histological response. An absence of histological remission could only be excluded at physiological levels of FC.

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ObjectiveHistological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems—Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels.DesignBiopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients’ Mayo Endoscopic Score and FC levels.ResultGS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa.ConclusionsGS, NI and RHI histopathological scoring systems are comparable in what concerns patients’ stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.

Patients with inflammatory bowel disease present a higher risk of colorectal cancer, especially patients with a high degree of disease activity. Although rare, carcinoid tumors can also be associated with inflammatory bowel disease. Mixed adenoneuroendocrine tumor is defined as a neoplasm with dual differentiation (neuroendocrine and adenoma) with each component accounting for at least 30% of the tumor. We present a case of a mixed adenoneuroendocrine tumor in a patient with inflammatory bowel disease.

Background: Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab. Methods: We conducted an open-label single-arm multicentre prospective study. At screening/baseline, week 6 (W6) and week 16 (W16), clinical and endoscopic activity (total Mayo score), histologic activity (Geboes index) and biomarkers were evaluated. Results: From 38 patients, 34 (89.5%) completed W6 and 29 (76.3%) completed W16. Mean age (±SD) was 34.6 ± 12.6 years; 55.9% were female. At W16, 62.1% achieved clinical response. Patients with endoscopic activity at W6 ( n = 20) had higher baseline sST2 (median, 24.5 versus 18.7 ng/ml, p = 0.026) and no decrease from baseline (median change, 0.8 versus −2.7, p = 0.029). At W6, sST2 levels correlated with endoscopic activity ( rs = 0.45, p = 0.007) but not with histological activity ( rs = 0.25, p = 0.151). The best cut-offs for endoscopic activity were sST2 = 16.9 ng/ml (sensitivity = 85%; specificity = 71%) and faecal calprotectin (FC) = 353 μg/g (sensitivity = 90%, specificity = 67%). Patients with histological activity at W6 ( n = 27) had higher baseline ST2 levels (median, 23.0 versus 13.7 ng/ml, p = 0.035). sST2 did not correlate with FC or serum C-reactive protein. FC levels correlated with histological activity and baseline FC were higher when Geboes ⩾3.1 at W6. Conclusions: sST2 may be a surrogate biomarker of UC activity and therapeutic response as it correlates with endoscopic and clinical activity at W6 of golimumab treatment, and subjects with endoscopic and histological activity at W6 had higher baseline ST2 levels.

Background: Resistant Hypertension (RH) is associated with an increased risk of cardiovascular events and poor prognosis. Exercise training studies in RH patients have shown promising outcomes, nonetheless, none determine the impact of exercise on endothelial damage and repair. Circulating endothelial cells (CECs) are a reliable indicator of vascular damage and dysfunction. Recent studies in hypertension suggest that increased levels of endothelial progenitor cells (EPCs), a marker of endothelial repair, are related to increased CECs in order to compensate endothelial damage. Purpose: This study aimed to determine the effect of 12-week aerobic exercise program on the percentage of EPCs and CECs in RH patients. Methods: Patients with RH were randomized to a 12-week aerobic exercise program (3 xs/week) (n = 13) and a usual care control group (n = 8). Outcome measures included clinical data, ambulatory blood pressure data and circulating levels of EPCs, hematopoietic stem cells (HSC) and CECs, quantified by flow cytometry. (ClinicalTrials.gov: NCT03090529). Results: Baseline characteristics were similar between groups, including the number of antihypertensive drugs (5.0 ± 0.9 vs. 4.8 ± 0.7, p = 0.517). After 12 weeks, no significant changes were found in the levels of HSCs in both groups. The levels of CECs decreased in the exercise group [0.0073 (0.0016)% to 0.0058 (0.0029), p = 0.019]; no changes were observed in the control group. EPC’s decreased only in the exercise group [0.0071 (0.0027)% to 0.0052 (0.0037)%, p = 0.046]. Conclusions: Exercise training reduces endothelial injury/damage (reduced CECs levels) in RH patients, a specific group who is a challenge for clinicians as the available treatment options have reduced success.

Objective: Carotid-femoral Pulse Wave velocity (cfPWV), the gold standard for measuring stiffness, is a marker of organ damage (OLD). Even though cfPWV correlates with casual (BPc), central (CBP) and ambulatory (ABPM) blood pressure (BP), evidence is limited for resistant hypertension (RH). Method: Thirty-three patients (age, 56.1 ± 8.2 years; weight, 78.0 ± 12.4 kg; height, 1.62 ± 0.08 m) with RH participated in a cross-sectional study. Outcomes included clinical data, BPc, ABPM, and carotid-femoral, cfPWV. Correlation analysis was conducted to assess the association between variables; independent t-tests were conducted to compare variables between those participants with cfPWV < and ≥ 10 m/s. Results: Patients (20 women and 13 men) presented a peripheral systolic and diastolic BPc of 144.0 ± 3.8 mmHg and 82.0 ± 1.9 mmHg, respectively. The cfPWV correlated with age (r = 0.356, p = 0.045), 24 h systolic BP (24 h SBP) nightime pulse pressure (night PP), 24 h pulse pressure (24hPP), casual systolic (SBPc) and diastolic BP (DBPc), central systolic (CSBP), diastolic (CDBP) and central pulse pressure (CPP); controlled for age the correlation remained significant for 24h SBP (r=0.446, p=0.009) 24hPP (r=0.464, p=0.007), nightPP (r=0.365, p=0.036), SBPc (r=0.620, p

Background: The relationship between arterial stiffness, blood pressure (BP) and cardiorespiratory fitness (CRF) has been studied in healthy populations and cardiovascular patients, since all of which proved to be independent predictors of all-cause mortality. We aimed to investigate the association of CRF with arterial stiffness and peripheral and central hemodynamics, in patients with resistant hypertension (RT). Methods: In this cross-sectional study, 30 patients (13 men, 17 women; age, 57.7 ± 8.1 years; weight, 79.2 ± 11.6 kg; body mass index, 29.7 ± 4.0 kg/m2) with resistant hypertension were recruited in the Hospital Infante D. Pedro (Aveiro) and Hospital Pedro Hispano (Matosinhos). Outcome measures included CRF (VO2peak), peripheral and central BP, and carotid-femoral pulse wave velocity (cf-PWV). Correlation analysis was conducted to assess the association between variables. Results: A significant negative correlation was found between VO2peak (33.7 ± 6.2 mLO2/kg/min) and central (141.0±21.3 mmHg; r = −0.395, p = 0.031) and peripheral systolic BP (148.4 ± 21.3 mmHg; r = −0.363, p = 0.049). VO2peak was also correlated with pulse pressure (PP) amplification ratio (1.2 ± 0.1 mmHg; r = 0.361, p = 0.050). The association with central systolic BP (r = −0.403, p = 0.035) and PP amplification ratio (r = 0.408, p = 0.033) remained significant after adjusted for age. VO2peak showed no correlation with PWV (9.4 ± 2.9 m/s; r = −0.075, p = 0.694) and peripheral (88.1 ± 12.2 mmHg; r = −0.138 p = 0.467) and central diastolic BP (88.5 ± 12.7 mmHg; r = −0.133, p = 0.483). Conclusion: This study confirms the inverse relationship between CRF and central systolic BP and PP amplification ratio in RH patients, regardless of age.

BACKGROUND Endoscopic recurrence after surgery for Crohn's disease (CD) is high, and it has important prognostic value. Crohn's disease will recur in the majority of patients after surgery. Fecal calprotectin (FC) and lactoferrin (FL) have attracted interest in the postoperative setting for predicting relapse. We have evaluated the accuracy of FC and FL in diagnosing endoscopic recurrence (ER) using the modified Rutgeerts score (MRS) compared with the Rutgeerts score (RS). METHODS A series of consecutive patients who underwent ileocolonic resection for Crohn's disease were evaluated. Biomarkers, clinical indexes, and fecal markers were recorded on the day of ileocolonoscopy. ER was defined as a MRS ≥ i2b or a RS ≥ i2. RESULTS Ninety-nine patients were included in this prospective cohort. The median time between surgery and colonoscopy was 87.5 months (IQR, 31-137). FC and FL levels were higher in patients with ER than in those in remission (Median FC, 196.5 μg/g [IQR, 96-634 μg/g] versus 42.1 μg/g [IQR 19-91.60 μg/g; P < 0.001]; Median FL, 23.27 μg/g [IQR 8.9-47.8 μg/g] versus 2 μg/g [IQR 0.9-7.26 μg/g; P < 0.001]). Using the MRS, 34% of patients presented with ER compared with 76% if the RS was used. The RS performed worse than the MRS with a decrease in sensitivity (74% versus 48% for FC and 85% versus 55% for FL) and in NPV (91% versus 33% for FC, and 90% versus 37% for FL). Furthermore, the accuracy of the MRS was higher than that of the RS (75% versus 55%). CONCLUSIONS Both FC and FL proved to correlate well with endoscopic findings in the evaluation of Crohn's disease after surgery. Both markers predicted recurrence with greater accuracy when the MRS was used. Fecal markers can be used to monitor disease recurrence after intestinal resection, with patients being selected to undergo further endoscopic evaluation.