Cross-reactivity patterns of T cells specific for iodinated contrast media

BACKGROUND: Approximately 3% of patients exposed to iodinated contrast media develop delayed hypersensitivity reactions. OBJECTIVE: We wanted to better understand the molecular basis of contrast media cross-reactivity. METHODS: Cross-reactivity was assessed by skin testing and measurement of T-cell activation (CD69 upregulation) and proliferation ((3)H-thymidine uptake, 5,6-carboxyfluorescein diacetate succinimidyl ester staining) of PBMCs, T-cell lines, and T-cell clones of 2 patients with delayed hypersensitivity reactions to iohexol and iomeprol, respectively. Thirteen different contrast media and potassium iodide were compared. RESULTS: Skin testing and analyses of PBMCs, T-cell lines, and clones showed broad cross-reactivity in both patients. Broad as well as more restricted cross-reactivity patterns were found in iohexol-specific and iomeprol-specific CD4(+) T-cell clones, whereas 1 iomeprol-specific CD8(+) T-cell clone showed no cross-reactivity at all. The reactivity to equimolar concentrations of iohexol and its dimer iodixanol was very similar, suggesting that the dimer was not more stimulatory than its monomer. Consistently low reactivity to iobitridol was found in both patients, but never to iodide. A frequency analysis of contrast medium-specific peripheral T cells gave values between 0.6 % (iomeprol) and 0.05 % (iobitridol). CONCLUSION: Clinically observed cross-reactivity between different contrast media is a result of the presence of contrast media-specific T cells, some of which show a broad cross-reactivity pattern. Iodide ions, known to be present at low concentration in contrast media solutions, do not seem to be the causative moiety. CLINICAL IMPLICATIONS: Detailed in vitro analysis might help identify noncross-reactive contrast media.     

Clinical and pharmacokinetic comparison of 2 oral preparations of nifedipine: 10 mg capsules and 20 mg delayed-release tablets

The effects and pharmacokinetic parameters of two oral formulations of nifedipine, 10 mg capsule (Adaltat) and 20 mg slow release tablet (Adalat a.p.). With the 10 mg capsule nifedipine was rapidly absorbed, reaching a maximum concentration of 120 +/- 39 ng/ml in 0.52 +/- 0.07 h, and also rapidly eliminated with an apparent halflife of 5.51 +/- 0.64 h. A fall in blood pressure and a raise in heart rate, that significantly correlated with plasma levels, were observed. 83% of the subjects reported headache, that was probably due to the sudden increase in plasma levels. With the 20 mg slow release tablet nifedipine absorption was slower, reaching a maximum concentration of 39 +/- 7 ng/ml in 1.82 +/- 0.43 h, and the apparent half-life (16.89 +/- 3.14 h) was longer than with the capsule. A fall in blood pressure was observed that significantly correlated with plasma levels; however, there was no significant correlation between these and changes in heart rate. Only 17% of the subjects reported headache. Pharmacokinetic data indicate that, in most subjects, nifedipine therapeutics plasma levels (over 15 ng/ml) can be maintained with the administration of a 20 mg slow release tablet every 12 hours. This, joined to the reduction in side effects, suggest that this formulation is the adequate alternative in chronic treatments with nifedipine, such as arterial hypertension.     

Bilateral pectoralis muscle advancement flap in the management of deep sternal wound infection: a single clinic study of clinical outcome and postoperative quality of life

Background

Poststernotomy mediastinitis is a serious complication after open heart surgery. There are currently no specific guidelines with regards to standard treatment.

Methods

This is a prospective cohort study using a source population of 7842 patients who underwent open heart surgery. Between 1999 and 2010, 83 patients were diagnosed with mediastinitis, of which 24 patients underwent reconstruction with bilateral pectoralis major advancement flap. All surviving patients were seen at follow-up, and postoperative functional level was examined. The closing date was October 1, 2011.

Results

Median follow-up time from primary operation was 6.0 (1.6–15.5) years. Median follow-up from postsurgical mediastinitis was26 5.4 (0.4–12.4)years. There was no early mortality, and 22 patients were discharged with complete wound closure and infection control. Quality of life questionnaires revealed significant morbidity with chronic pain and reduced mobility, but despite this, patients were satisfied with their overall health outcome.

Conclusions

Mediastinitis remains a serious postoperative complication after open heart surgery accounting for significant morbidity and mortality. Treatment of deep sternal wound infection by pectoralis major flap reconstruction gives excellent wound closure. Follow-up showed that these patients were multimorbid with reduced quality of life as measured. Level of Evidence: Level IV, therapeutic study.     

Effect of different episiotomy techniques on perineal pain and sexual activity 3 months after delivery

Introduction and hypothesis

The effect of different episiotomy techniques on pain perception 3 months after delivery is unknown. Study aims were to explore the association between different episiotomy techniques and perineal pain 3 months after delivery and to assess female sexual activity in relation to episiotomy technique.

Methods

This is a prospective observational study, designed to investigate short- and long-term complications of different episiotomy techniques. All 300 participants were recruited and clinically examined during their postpartum hospital stay in order to evaluate episiotomy performance. A 3-month follow-up questionnaire addressing pain, sexual activity, and puerperal wound infection was distributed to 208 women who had scored perineal pain in a personal interview the first day after delivery.

Results

A response rate of 87.7 % was obtained. We found no difference in pain score distribution by Visual Analogue Scale (VAS) when comparing midline, mediolateral, and lateral episiotomy techniques (p?=?0.32) or between midline and lateral incision points (p?=?0.58). Dyspareunia was reported by 33 out of 179 women, but no difference between episiotomy techniques (p?=?0.90), or between episiotomy incision points (p?=?0.14), was found. Perineal wound infection was reported by 9.5 %, but there was no significant difference between episiotomy techniques (p?=?0.73).

Conclusions

No difference was found in perineal pain perception 3 months postpartum between different episiotomy techniques or when comparing midline and lateral incision points. Dyspareunia was not associated with any particular episiotomy technique or incision point.     

Bottle‐feeding an infant feeding modality: An integrative literature review

Bottle‐feeding is an infant feeding modality that has been in existence since ancient times, and currently, a significant number of infants are being fed via a bottle with either breastmilk or formula. Although research on bottle‐feeding has continued, it exists in fragmented, often small studies that focus on singular aspects of feeding an infant using a bottle, with limited information on the bottle‐feeding act. Systems theory was the approach used to define the act of bottle‐feeding and identify the parts within this act. Health databases were searched using MeSH terms. A summary of the studies are included. The findings of this review revealed that healthy term bottle‐feeding infants use similar tongue and jaw movements, can create suction and sequentially use teat compression to obtain milk, with minimal differences in oxygen saturation and SSB patterns, when compared with breastfeeding infants. Bottle and teat characteristics were revealed to affect infant feeding and milk intake. An infant's milk intake during feeding was shown to have a strong association with the interaction between the infant and parent/caregiver. With the issue of who controls the feed, mother or infant, likely to affect an infant's ability to self‐regulate their milk intake. Redefining bottle‐feeding as a holistic system identifies the interrelationship of the various parts which will improve the understanding of the reciprocal nature of infant feeding. To optimize bottle‐feeding outcomes, further research is required on parents' and health professionals' knowledge and understanding of the parts within the act of bottle‐feeding.     

Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors

This study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition. This was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD. Adverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses). Continuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested.     

Health status in patients at risk of inherited arrhythmias and sudden unexpected death compared to the general population

Background  

The possibilities in the molecular genetics of long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM) has made family screening, with diagnostic and predictive genetic testing part of the health care offer in genetic counselling of inherited arrhythmias, potentially affecting the subjective health among these individuals. The study compared health status among patients at risk of arrhythmia because of family history or clinical diagnosis of LQTS and HCM with reference health status scores of the general population.