Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.

BACKGROUND: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. METHODS: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. RESULTS: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1 -q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11). CONCLUSIONS: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.

Prevalence and predictors of arthralgia after initiation of vedolizumab in patients with inflammatory bowel disease: a retrospective cohort study.

OBJECTIVES: Vedolizumab is a mAb used for the treatment of moderate to severe ulcerative colitis and Crohn's disease. There is evidence that administration of vedolizumab has been associated with either new onset or reactivation of extra-intestinal manifestations, among which arthralgia is the most prominent. We aimed to study the incidence, characteristics and predictors for the occurrence of arthralgias in patients with inflammatory bowel disease (IBD) who receive vedolizumab. METHODS: A retrospective cohort study was implemented in patients with IBD. The occurrence of new-onset and recurrent arthralgias were recorded. Multivariate Cox proportional-hazards models were used to identify factors associated with the endpoints of interest. RESULTS: A total of 115 vedolizumab-treated IBD patients (male = 50.4%; ulcerative colitis = 70.4%; median follow-up = 12.7 months) participated. New-onset arthralgia occurred in 20.9%, and recurrent in 46.7% (45 patients at risk). Among patients with ulcerative colitis, multivariate Cox's proportional-hazards models showed, that new onset arthralgia was significantly associated with extensive colitis (hazard ratio = 2.91; 95% confidence interval, 1.04-8.12). Of 15 patients with concomitant treatment of azathioprine, no one manifested new-onset arthralgia (X2P = 0.03; Fisher's exact test P = 0.038). No predictors were identified for recurrent arthralgia. CONCLUSION: Arthralgias is a common manifestation of vedolizumab treatment. Patients with extensive ulcerative colitis demonstrate a higher risk for new-onset arthralgia, whereas, concomitant treatment with azathioprine appears to be protective. These associations may be mediated by re-directed lymphocyte trafficking and may support concomitant immunomodulator administration in specific patient subpopulations who commence treatment with vedolizumab.

Patients With Inflammatory Bowel Diseases Have Impaired Antibody Production After Anti-SARS-CoV-2 Vaccination: Results From a Panhellenic Registry.

BACKGROUND: Four EMA-approved vaccines against SARS-CoV-2 are currently available. Data regarding antibody responses to initial vaccination regimens in patients with inflammatory bowel diseases (IBD) are limited. METHODS: We conducted a prospective, controlled, multicenter study in tertiary Greek IBD centers. Participating patients had completed the initial vaccination regimens (1 or 2 doses, depending on the type of COVID-19 vaccine) at least 2 weeks before study enrolment. Anti-S1 IgG antibody levels were measured. Demographic and adverse events data were collected. RESULTS: We tested 403 patients (Crohn's disease, 58.9%; male, 53.4%; median age, 45 years) and 124 healthy controls (HCs). Following full vaccination, 98% of patients seroconverted, with mRNA vaccines inducing higher seroconversion rates than viral vector vaccines (P = .021). In total, IBD patients had lower anti-S1 levels than HCs (P < .001). In the multivariate analysis, viral vector vaccines (P < .001), longer time to antibody testing (P < .001), anti-TNFα treatment (P = .013), and age (P = .016) were independently associated with lower anti-S1 titers. Vedolizumab monotherapy was associated with higher antibody levels than anti-TNFα or anti-interleukin-12/IL-23 monotherapy (P = .023 and P = .032). All anti- SARS-CoV-2 vaccines were safe. CONCLUSIONS: Patients with IBD have impaired antibody responses to anti-SARS-CoV-2 vaccination, particularly those receiving viral vector vaccines and those on anti-TNFα treatment. Older age also hampers antibody production after vaccination. For those low-response groups, administration of accelerated or prioritized booster vaccination may be considered.

Thisis a multicenter study on IBD patients after COVID-19 vaccination and anti-S1 IgG antibody levels measurement. Patients with IBD have lower antibody responses than healthy controls, particularly those receiving viral vector vaccines and those on anti-TNFα or combination treatment.

Real-World Use and Adverse Events of SARS-CoV-2 Vaccination in Greek Patients with Inflammatory Bowel Disease.

Since inflammatory bowel disease (IBD) patients were excluded from vaccine authorization studies, limited knowledge exists regarding perceptions and unfavorable effects of COVID-19 vaccination in this group. We aimed to investigate the real-world use and adverse events (AEs) of COVID-19 vaccines in Greek IBD patients. Fully vaccinated IBD patients followed in Greek centers were invited to participate. All patients filled out an anonymous online survey concerning the vaccination program, which included information regarding demographics, clinical characteristics, treatment, vaccination perceptions and potential AEs. Overall, 1007 IBD patients were included. Vaccine hesitancy was reported by 49%. Total AEs to vaccination were reported by 81% after dose 1 (D1) and 76% after dose 2 (D2), including isolated injection site reactions (36% and 24% respectively). Systemic AEs were more common after D2 (51%, D2 vs. 44%, D1, p < 0.0001). Very few patients reported new onset abdominal symptoms (abdominal pain 4% (D1), 6% (D2) and diarrhea 5% (D1), 7% (D2)). There were no serious AEs leading to emergency room visit or hospitalization. In multivariate analysis, AEs occurrence was positively associated with young age and female gender (p < 0.0005 for both doses), whereas inactive disease was negatively associated with AE in D1 (p = 0.044). SARS-CoV-2 vaccination in Greek IBD patients demonstrated a favorable and reassuring safety profile.

Health-Related Quality of Life and Cosmesis After Thyroidectomy: Long-Term Outcomes.

BACKGROUND: Health-related quality of life (HRQoL) after thyroidectomy has been recently reported with conflicting conclusions. In this study, we assess HRQoL and neck scar cosmesis of thyroid patients several years after thyroidectomy for benign and malignant pathology. METHODS: Three hundred and thirty patients who underwent thyroidectomy between 2000 and 2010 answered the SF-36 Health Survey and Patient Scar Assessment Questionnaire (PSAQ) in 2010 and at the end of 2018. Changes in the SF-36 and PSAQ scores were analyzed taking into account various demographic, surgical and medical characteristics of the patients. RESULTS: Patients reported worse SF-36 scores after 8.5 years, in scales of physical functioning (p < 0.001), social role functioning (p = 0.002), bodily pain (p = 0.001) and general health perceptions (p < 0.001). Interestingly enough, there were no significant changes in scales of physical role functioning (p = 0.304), mental health (p = 0.681), emotional role functioning (p = 0.903) and vitality (p = 0.121). Multivariate analysis showed that several chronic diseases were related to worse HRQoL scores. On the other hand, PSAQ appearance, symptoms and consciousness scores improved during this period (p < 0.001). CONCLUSIONS: In the long term, patients undergoing thyroidectomy do not show worse HRQoL outcomes in terms of mental health, emotional functioning and vitality, whereas scar cosmesis perception is improved. They show deteriorated outcomes in terms of physical, social functioning and bodily pain, which is mainly related to specific chronic diseases that are common to the aging person.

Factors influencing arrival of patients with acute myocardial infarction at emergency departments: implications for community nursing interventions.

AIM: This paper identifies the characteristics of Greek patients with acute myocardial infarction who have long prehospital delays and identifies the factors that are specifically associated with these delays. BACKGROUND: The time between the first appearance of symptoms until the hospitalization of the patient with myocardial infarction correlates statistically significantly with in-hospital and long-term mortality. METHODS: The study took place in two Greek coronary care units from 1 June 2007 to 31 July 2008. From 232 consecutive patients with myocardial infarction, 160 were enrolled. Data were collected by a trained hospital staff nurse, who interviewed all patients within 48 hours of hospital admission. RESULTS: Smokers arrived statistically significantly sooner at the hospital than non-smokers [smokers' prehospital time delay: 78.9 (sd = 3.2) minutes vs. non-smokers' prehospital time delay: 98.2 (sd = 4.1) minutes, Mann-Whitney U-test, Z = -2.5, P < 0.05]. Patients with hyperlipidaemia arrived with a mean delay of 13 minutes less than normolipidaemic patients. Those with inferior ST segment elevation myocardial infarction exhibited statistically significantly shorter delay times than those with anterior or lateral (inferior vs. anterior, P = 0.003, inferior vs. lateral, P = 0.024, anova with Bonferroni-Holm post hoc test, F = 7.5, P = 0.001). CONCLUSION: Community nurses should educate all patients about myocardial infarction, not only those at high risk but also those without known risk factors for ischaemic heart disease.

Nitroglycerin and epinephrine improve coronary perfusion pressure in a porcine model of ventricular fibrillation arrest: a pilot study.

BACKGROUND: Cardiac arrest remains one of the leading causes of death worldwide. European Resuscitation Council Guidelines for Resuscitation 2005 recommend epinephrine for its treatment. OBJECTIVES: To estimate whether the administration of a vasodilatator such as nitroglycerin in combination with epinephrine during cardiopulmonary resuscitation would improve resuscitation outcome in an established model of ventricular fibrillation. DESIGN: Prospective, randomized, blinded, controlled study. SETTING: Animal research laboratory. Ventricular fibrillation was induced in 20 Landrace/Large-White pigs. It remained untreated for 8 min before attempting resuscitation precordial compressions, mechanical ventilation, and electrical defibrillation. Animals were randomized into two groups, 10 animals each. Group A received saline as placebo (10 mL dilution, bolus) and epinephrine (0.02 mg/kg). Group B received nitroglycerin (50 microg/kg) and epinephrine (0.02 mg/kg) during cardiopulmonary resuscitation. Electrical defibrillation was attempted after 10 min of ventricular fibrillation. RESULTS: Four animals in group A restored spontaneous circulation in comparison to eight in Group B. Coronary perfusion pressure (p < 0.0001) was significantly increased in Group B during cardiopulmonary resuscitation. CONCLUSION: A vasodilatator, when administered in combination with a vasopressor such as epinephrine during cardiopulmonary resuscitation, increases coronary perfusion pressure.

Vasopressin and epinephrine in the treatment of cardiac arrest: an experimental study.

BACKGROUND: Epinephrine remains the drug of choice for cardiopulmonary resuscitation. The aim of the present study is to assess whether the combination of vasopressin and epinephrine, given their different mechanisms of action, provides better results than epinephrine alone in cardiopulmonary resuscitation. METHODS: Ventricular fibrillation was induced in 22 Landrace/Large-White piglets, which were left untreated for 8 minutes before attempted resuscitation with precordial compression, mechanical ventilation and electrical defibrillation. Animals were randomized into 2 groups during cardiopulmonary resuscitation: 11 animals who received saline as placebo (20 ml dilution, bolus) + epinephrine (0.02 mg/kg) (Epi group); and 11 animals who received vasopressin (0.4 IU/kg/20 ml dilution, bolus) + epinephrine (0.02 mg/kg) (Vaso-Epi group). Electrical defibrillation was attempted after 10 minutes of ventricular fibrillation. RESULTS: Ten of 11 animals in the Vaso-Epi group restored spontaneous circulation in comparison to only 4 of 11 in the Epi group (p = 0.02). Aortic diastolic pressure, as well as, coronary perfusion pressure were significantly increased (p < 0.05) during cardiopulmonary resuscitation in the Vaso-Epi group. CONCLUSION: The administration of vasopressin in combination with epinephrine during cardiopulmonary resuscitation results in a drastic improvement in the hemodynamic parameters necessary for the return of spontaneous circulation.