Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update

In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

One MAC of sevoflurane provides protection against reperfusion injury in the rat heart in vivo

Volatile anaesthetics protect the heart against reperfusion injury. We investigated whether the cardioprotection induced by sevoflurane against myocardial reperfusion injury was concentration-dependent. Fifty-eight alpha-chloralose anaesthetized rats were subjected to 25 min of coronary artery occlusion followed by 90 min of reperfusion. Sevoflurane was administered for the first 15 min of reperfusion at concentrations corresponding to 0.75 (n=11), 1.0 (n=11), 1.5 (n=13), or 2.0 MAC (n=12). Eleven rats served as untreated controls. Left ventricular peak systolic pressure (LVPSP, tipmanometer) and cardiac output (CO, flowprobe) was measured. Infarct size (IS, triphenyltetrazolium staining) was determined as percentage of the area at risk. Baseline LVPSP was 131 (126-135) mm Hg (mean (95% confidence interval)) and CO 33 (31-36) ml min(-1), similar in all groups. During early reperfusion, sevoflurane reduced LVPSP in a concentration-dependent manner to 78 (67-89)% of baseline at 0.75 MAC (not significant vs controls 99 (86-112)%), 71 (62-80)% at 1 MAC (P <0.05), 66 (49-83)% at 1.5 MAC (P <0.05) and 56 (47-65)% at 2 MAC (P <0.05). CO remained constant. While 0.75 MAC of sevoflurane had no effect on IS (34 (27-41)% of the area at risk) compared with controls (38 (31-45)%, P=0.83), 1.0 MAC reduced IS markedly to 23 (17-30)% (P <0.05). Increasing the concentration to 1.5 MAC (23 (17-30)%) and 2 MAC (23 (13-32)%, both P <0.05 vs controls) had no additional protective effect. One MAC sevoflurane protected against myocardial reperfusion injury. Increasing the sevoflurane concentration above 1 MAC resulted in no further protectio

Congenital diaphragmatic eventration and hernia sac compared to CDH with true defects: a retrospective cohort study

Contains fulltext : 220757.pdf (Publisher’s version ) (Open Access)Congenital diaphragmatic eventration (CDE) and congenital diaphragmatic hernia (CDH) with or without hernia sac are three different types of congenital diaphragmatic malformations, which this study evaluates. All surgically treated patients with CDE or Bochdalek type CDH between 2000 and 2016 were included in this retrospective analysis. Demographics, CDH-characteristics, treatment, and clinical outcome were evaluated. In total, 200 patients were included. Patients with an eventration or hernia sac had no significant differences and were compared as patients without a true defect to patients with a true defect. The 1-year survival of patients with a true defect was significantly lower than patients with no true defect (76% versus 97%, p = 0.001). CDH with no true defect had significantly better short-term outcomes than CDH with true defect requiring patch repair. However, at 30 days, they more often required oxygen supplementation (46% versus 26%, p = 0.03) and had a higher recurrence rate (8% versus 0%, p = 0.006) (three eventration and two hernia sac patients). Conclusion: Patients without a true defect seem to have a more similar clinical outcome than CDH patients with a true defect, with a better survival. However, the recurrence rate and duration of oxygen supplementation at 30 days are higher than CDH patients with a true defect.What is Known:* Congenital diaphragmatic hernia with or without hernia sac and congenital diaphragmatic eventration (incomplete muscularization) are often treated similarly.* Patients with hernia sac and eventration are thought to have a relatively good outcome, but exact numbers are not described.What is New:* Congenital diaphragmatic eventration and patients with hernia sac seem to have a more similar clinical outcome than Bochdalek type CDH with a true defect.* Patients without a true defect (eventration or hernia sac) have a high recurrence rate

The impact of prior biologic therapy on adalimumab response in patients with rheumatoid arthritis.

OBJECTIVES: The aim of this study is to use data from a non-interventional study of adalimumab in patients with rheumatoid arthritis (RA) during routine clinical practice to evaluate the impact of prior treatment with biologics on the effectiveness of current therapy. METHODS: Efficacy parameters were evaluated for all patients with values at baseline and month 12. Subgroup analyses were performed on patients with 0, 1, or ≥2 prior biologic agents. Key outcome measures included Disease Activity Score- 28 joints (DAS28) and Funktionsfragebogen Hannover (FFbH) functional ability score. RESULTS: A total of 4700 RA adalimumab-treated patients were included in this analysis. Baseline disease activity increased with an increasing number of prior biologic agents and therapeutic response diminished. After 12 months of adalimumab therapy, DAS28 and FFbH scores showed improvements in all groups, but the group with 0 prior biologic agents had the best outcomes, while the group with ≥2 prior biologic agents had the worst. Clinical response (EULAR and DAS28-dcrit) and remission rates showed a similar pattern. Nevertheless, 44% to 67% of patients treated with ≥2 prior biologic agents achieved a clinical response. Multiple regression analyses identified prior biologic therapy as a significant negative predictor for response to therapy. CONCLUSIONS: Treatment with adalimumab leads to decreases in disease activity and improvements in function. Improvements are most pronounced in patients with 0 or 1 prior biologic agent, but a substantial proportion of patients treated with ≥2 prior biologic agents experience significant benefit from adalimumab therapy

Defining outcomes following congenital diaphragmatic hernia using standardised clinical assessment and management plan (SCAMP) methodology within the CDH EURO consortium

Contains fulltext : 200036.pdf (publisher's version ) (Closed access)Treatment modalities for neonates born with congenital diaphragmatic hernia (CDH) have greatly improved in recent times with a concomitant increase in survival. In 2008, CDH EURO consortium, a collaboration of a large volume of CDH centers in Western Europe, was established with a goal to standardize management and facilitate multicenter research. However, limited knowledge on long-term outcomes restricts the identification of optimal care pathways for CDH survivors in adolescence and adulthood. This review aimed to evaluate the current practice of long-term follow-up within the CDH EURO consortium centers, and to review the literature on long-term outcomes published from 2000 onward. Apart from having disease-specific morbidities, children with CDH are at risk for impaired neurodevelopmental problems and failure of educational attainments which may affect participation in society and the quality of life in later years. Thus, there is every reason to offer them long-term multidisciplinary follow-up programs. We discuss a proposed collaborative project using standardized clinical assessment and management plan (SCAMP) methodology to obtain uniform and standardized follow-up of CDH patients at an international level