Mortality and Long-Term Outcome of Neonates with Congenital Heart Disease and Acute Perinatal Stroke: A Population-Based Case-Control Study

Objective: Neonates with congenital heart disease (CHD) and perinatal stroke have high mortality and survivors are at risk for poor long-term neurodevelopmental outcome. The aim of this study was to assess the risk factors and outcome of neonates with both CHD and MRI-confirmed perinatal stroke (Study Group) and compare those to the risk factors and outcome of infants matched for CHD without stroke (Control-1) and of infants matched for MRI-confirmed stroke without CHD (Control-2). Methods: We conducted a population-based case-control study enrolling 28 term neonates with CHD and MRI-confirmed acute perinatal stroke born between 2007–2017 in the Central-Hungarian Region. Each of the control groups included 56 infants. The Bayley Scales of Infant Development-II, the Brunet-Lézine test and the Binet Intelligence scales-V were used for neurodevelopmental follow-up at a median age of 61 months. Results: Mortality was highest in the Study Group (25% compared to 5% and 2%, respectively, p = 0.001). Adverse neurodevelopmental outcome was prevalent in the Study (53%) and Control-2 Groups (52%, p = 0.03). Significantly different parameters among the three groups included Apgar scores, mode of delivery, gestational age at birth, cardiac interventions and twin pregnancy. In a multivariable regression analysis adjusted for clinically relevant parameters, patients in the Study Group had significantly higher odds for mortality compared to patients in the Control-1 Group (OR: 6.5 95% CI: 1.1–39.4). Conclusions: Neonates with perinatal stroke and CHD are at a higher risk for dying compared to neonates with CHD without stroke. In addition, the stroke-associated direct insult to the brain likely plays an important role in the development of neurodevelopmental morbidity in these patients.     

Network meta-analysis of prophylactic pancreatic stents and non-steroidal anti-inflammatory drugs in the prevention of moderate-to-severe post-ERCP pancreatitis

BackgroundThere is an ongoing debate that non-steroidal anti-inflammatory drugs (NSAID) or prophylactic pancreatic stents (PPS) are more beneficial in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). In our present network meta-analysis, we aimed to compare PPSs to rectal NSAIDs in the prevention of moderate and severe PEP in average- and high-risk patients.MethodsWe performed a systematic search for randomized controlled trials (RCT) from MEDLINE (via PubMed), Embase and Cochrane Central databases. RCTs using prophylactic rectal NSAIDs or PPSs in patients subjected to ERCP at average- and high-risk population were included. The main outcome was moderate and severe PEP defined by the Cotton criteria. Pairwise Bayesian network meta-analysis was performed, and interventions were ranked based on surface under cumulative ranking (SUCRA) values.ResultsSeven NSAID RCTs (2593 patients), and 2 PPS RCTs (265 patients) in the average-risk, while 5 NSAID RCTs (1703 patients), and 8 PPS RCTs (974 patients) in the high-risk group were included in the final analysis. Compared to placebo, only PPS placement reduced the risk of moderate and severe PEP in both patient groups (average-risk: RR = 0.07, 95% CI [0.002–0.58], high-risk: RR = 0.20, 95% CI [0.051–0.56]) significantly. Rectal NSAID also reduced the risk, but this effect was not significant (average-risk: RR = 0.58, 95% CI [0.22–1.3], high-risk: RR = 0.58, 95% CI [0.18–2.3]). Based on SUCRA, PPS placement was ranked as the best preventive method.ConclusionProphylactic pancreatic stent placement but not rectal NSAID seems to prevent moderate-to-severe PEP better both, in average- and high-risk patients.     

Evidence for a lipochaperonin: Association of active proteinfolding GroESL oligomers with lipids can stabilize membranes under heat shock conditions

During heat shock, structural changes in proteins and membranes may lead to cell death. While GroE and other chaperone proteins are involved in the prevention of stress-induced protein aggregation and in the recovery of protein structures, a mechanism for short-term membrane stabilization during stress remains to be established. We found that GroEL chaperonin can associate with model lipid membranes. Binding was apparently governed by the composition and the physical state of the host bilayer. Limited proteolysis of GroEL oligomers by proteinase K, which removes selectively the conserved glycine- and methionine-rich C terminus, leaving the chaperonin oligomer intact, prevented chaperonin association with lipid membranes. GroEL increased the lipid order in the liquid crystalline state, yet remained functional as a protein-folding chaperonin. This suggests that, during stress, chaperonins can assume the functions of assisting the folding of both soluble and membrane-associated proteins while concomitantly stabilizing lipid membranes.     

Effect of inhibitors of myeloperoxidase on the development of aortic atherosclerosis in an animal model

Our earlier studies have shown that some steroids increase myeloperoxidase enzyme (MPO) release from human granulocytes, and that MPO plasma levels are significantly lower in postclimacteric people. Moreover, we have proven that MPO inhibits production of atherogenic free radical superoxide anion and MPO-inhibitors increase superoxide release. The aim of the present study was to investigate the effect of MPO-inhibitors on the early phase of aortic atherosclerosis, namely the extent of intimal plaques and the thickening of the medial layer. Adult male rabbits were fed with lipid rich food (cholesterol: 1.3%, peanut oil: 8%) for 8 weeks. During this period MPO-inhibitors were also given (4-aminobenzoicacid-hydrazide/ABAH/-13.3 mg/kg/day or indometacin-5 mg/kg/day). All animals developed intimal lipid plaques (raised fatty streaks). The relative plaque-covered areas of the aortas were compared and the media thickness of the aorta was measured on plaque-free as well as plaque-containing areas. The medial smooth muscle density and peroxidase activity of the aortic media were also determined. The media thickness increased (p<0.05) in the cholesterol+ABAH as well as in the cholesterol+indometacin groups up to 375.7 (+/-60.5) and 442.5 (+/-123.4) microm, respectively, compared to the control group (cholesterol feeding alone) where it measured only 308.4 (+/-51.67) microm. The medial peroxidase activity decreased significantly in the indometacin treated group and showed a decreasing tendency using ABAH. In parallel to this there was a tendency of increase in the relative plaque covered areas. The smooth muscle density showed no significant modifications, while inhibitors of the MPO seemed to enhance aortic medial thickness, i.e. the grade of a pre-atherosclerotic lesion, in our animal model. Collectively, the anti-atherogenic effect of certain steroid hormones might be realized through the impact on MPO activity.     

Health outcomes of delayed union and nonunion of femoral and tibial shaft fractures

Introduction

Knowledge about the functional consequences of lower limb long bone fractures is helpful to inform patients, clinicians and employers about their recovery process and prognosis. This study aims to describe the epidemiology and health outcomes of femoral and tibial shaft fractures treated at two level I trauma centres, by comparing the differences between patients with delayed union or nonunion and patients with union.

Patients and methods

An analysis of registry data over two years, supplemented with medical record review, was conducted. Fracture healing was retrospectively assessed by clinical and radiological evidence of union, and the need for surgical intervention. SF-12 scores, and work and pain status were prospectively recorded at six and twelve months post injury.

Results

285 fractures progressed to union and 138 fractures developed delayed union or nonunion. There was a significant difference between the two cohorts with regards to the mechanism of injury, association with multi-trauma, open fractures, grade of Gustilo classification, patient fund source, smoking status and presence of comorbidities. The SF-12 physical component score was less than 50 at both six and twelve months with improvement in the union group, but not in the delayed union or nonunion group. 72% of patients with union had returned to work at one year, but 54% continued to have pain. The difference compared to patients with delayed union or nonunion was significant.

Discussion

Even patients whose fractures unite in the expectant time-frame will have residual physical disability. Patients with delayed union or nonunion have still poorer outcomes, including ongoing problems with returning to work and pain. It is important to educate patients about their injury so that they have realistic expectations. This is particularly relevant given that the patients most likely to sustain femoral or tibial shaft fractures are working-age healthy adults, and up to a third of fractures may develop delayed union or nonunion.

Conclusion

Despite modern treatment, the patient-reported outcomes of lower limb long bone shaft fractures do not return to normal at one year. Patients with delayed union or nonunion can expect poorer outcomes.