Postconditioning protects against endothelial ischemia-reperfusion injury in the human forearm

Background: Hypoxic cell death follows interruption of blood supply to tissues. Although successful restoration of blood flow is mandatory for salvage of ischemic tissues, reperfusion can paradoxically place tissues at risk of further injury. Brief periods of ischemia applied at the onset of reperfusion have been shown to reduce ischemia-reperfusion (IR) injury, a phenomenon called postconditioning. The aim of this study was to determine whether postconditioning protects against endothelial IR injury in humans, in vivo. Methods and Results: Brachial artery endothelial function was assessed by vascular ultrasound to measure flow-mediated dilation (FMD) in response to forearm reactive hyperemia. FMD was measured before and after IR (20 minutes of arm ischemia followed by 20 minutes of reperfusion) in healthy volunteers. To test the protective effects of postconditioning, 3 cycles of reperfusion followed by ischemia (each lasting 10 or 30 seconds) were applied immediately after 20 minutes of arm ischemia. To determine whether postconditioning needs to be applied at the onset of reperfusion, a 1-minute period of arm reperfusion was allowed before the application of the 10-second postconditioning stimulus. IR caused endothelial dysfunction (FMD 9.1±1.2% pre-IR, 3.6±0.7% post-IR, P<0.001; n=11), which was prevented by postconditioning applied as 10-second cycles of reperfusion/ischemia (FMD 9.9±1.7% pre-IR, 8.3±1.4% post-IR, P=NS; n=11) and 30-second cycles of reperfusion/ischemia (FMD 10.8±1.7% pre-IR, 9.5±1.5% post-IR, P=NS; n=10) immediately at the onset of reperfusion. No protection was observed when the application of the 10-second postconditioning stimulus was delayed for 1 minute after the onset of reperfusion (FMD 9.8±1.2% pre-IR, 4.0±0.9% post-IR, P<0.001; n=8). Conclusions: This study demonstrates for the first time that postconditioning can protect against endothelial IR injury in humans. Postconditioning might reduce tissue injury when applied at the onset of reperfusion by modifying the reperfusion phase of IR

Prolonged low flow reduces reactive hyperemia and augments low flow mediated constriction in the brachial artery independent of the menstrual cycle

© 2013 Rakobowchuk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Non-invasive forearm ischemia-reperfusion injury and low flow induced vascular dysfunction models provide methods to evaluate vascular function. The role of oestrogen, an endogenous anti-oxidant on recovery from ischemia-reperfusion injury has not been evaluated nor has the impact of prolonged low flow on vascular function been established. Eight healthy women (33610 yr) attended the lab during the follicular, ovulatory and mid-luteal phases of their menstrual cycles. After 30 minutes of rest, brachial artery vascular function was assessed by ultrasound measurements of diameter changes during 5 minutes of forearm ischemia and 3 minutes after. Subsequently, a 20-minute forearm ischemia period was completed. Further, vascular function assessments were completed 15, 30 and 45 minutes into recovery. Flow-mediated dilation, lowflow-mediated constriction, and reactive hyperaemia proximal to the area of ischemia were determined. Flow-mediated dilation was reduced at 15 minutes of recovery but recovered at 30 and 45 minutes (PRE: 7.161.0%, POST15:4.560.6%, POST30:5. 560.7% POST45:5.960.4%, p,0.01). Conversely, low-flow mediated constriction increased (PRE: 21.360.4%, POST15: 23.360.6%, POST30: 22.560.5% POST45: 21.560.12%, p,0.01). Reactive hyperaemia was reduced throughout recovery (p,0.05). Data were unaffected by menstrual phase. Prolonged low flow altered vascular function and may relate as much to increased vasoconstriction as with decreased vasodilation. Reductions in anterograde shear and greater retrograde shear likely modulate the brachial artery response, but the reduced total shear also plays an important role. The data suggest substantial alterations in vascular function proximal to areas of ischemia with potential clinical implications following reperfusion.British Heart Foundation (PG/08/060/25340),a Physiological Society summer studentship to SG, and a Wellcome Trust Vacation Studentship to EP

Indocyanine Green-Based Fluorescence-Guided Surgery in a Male Infant with Anorectal Malformation

Reconstructive techniques for complex anorectal malformations (ARMs) require intestinal pull-through on vascular pedicles. Traditionally, the visual inspection of the intestinal perfusion is the sole modality adopted to assess tissue viability. In this article, we report the case of a child with a rectourethral prostatic fistula, who had a Peña's descending colostomy with distal mucous fistula in the neonatal period and a posterior sagittal anorectoplasty at 6 months of life. The ARM repair was guided by indocyanine green (ICG), which was intravenously administered to evaluate the blood flow of the intestinal pull-through using the EleVision IR system (Medtronic Ltd, U.K.). ICG-based fluorescence-guided surgery helped to define the proximal resection margin, impacting intraoperative decision making, and no postoperative complications occurred. We envisage that this technology will become part of the armory of pediatric surgeons soon, by reducing the risk of intra- and postoperative complications

Congenital diaphragmatic hernia subtypes: Comparing birth prevalence, occurrence by maternal age, and mortality in a national birth cohort

BACKGROUND: Population-based administrative data have rarely been used to compare the birth prevalence, risk factors for occurrence, and mortality of congenital diaphragmatic hernia (CDH) subtypes. OBJECTIVES: We used a national birth cohort to identify CDH subtypes and compared their birth prevalence, relationship with maternal age after accounting for sociodemographic factors, and 1-year mortality rates. METHODS: Linked hospital admission and death records were used to identify isolated and complex CDH cases (involving additional anomalies) among singleton livebirths in England between 2002 and 2018. The prevalence of each CDH subtype per 10,000 livebirths was estimated overall and by infant, birth and maternal characteristics. The relationship between maternal age and each subtype relative to no CDH was examined using multivariable log-binomial regression to estimate risk ratios (RRs). One-year mortality rates were examined using Kaplan-Meier curves and the hazard ratio (HR) of complex versus isolated CDH was calculated using Cox regression. RESULTS: Among 9.5 million livebirths, we identified 1285 with isolated CDH and 1150 with complex CDH. The overall prevalence of isolated and complex CDH was 1.4 (95% confidence interval [CI] 1.3, 1.4) and 1.2 (95% CI 1.1, 1.3) per 10,000 livebirths, respectively. Only complex CDH was associated with maternal age. Compared with maternal age 25-34 years, complex CDH risk was elevated for maternal age < 20 years (RR 1.31, 95% CI 1.00, 1.72). Risk was highest for maternal age ≥ 40 years (RR 1.61, 95% CI 1.21, 2.15) although accounting for chromosomal anomalies attenuated the risk (RR 1.39, 95% CI 1.00, 1.92). The 1-year mortality rate for complex CDH (33.1%, 95% CI 30.5, 35.9) was slightly higher than for isolated CDH (29.7%, 95% CI 27.3, 32.3) (HR 1.10, 95% CI 0.96, 1.27). CONCLUSIONS: Mechanisms of occurrence differed between and within CDH subtypes and 1-year mortality of complex CDH was slightly higher than for isolated CDH

Variability and reproducibility of flow-mediated dilatation in a multicentre clinical trial

Aims The aim of this study was to assess the reproducibility of flow-mediated dilatation (FMD) in a multicentre setting. Methods and results This study was performed as part of the dal-VESSEL trial in which FMD was measured in 19 vascular imaging centres in six European countries. A subgroup of patients who were allocated in the placebo group and scanned twice at each trial time point (substudy) was analysed. Intra-sonographer variability was calculated from FMD measurements 48 h apart. Centre variability and short-, medium-, and long-term reproducibility of FMD were calculated at 48 h and at 3 and 9 months intervals, respectively. Intra- and inter-reader variability was assessed by re-analysing the FMD images by three certified readers at two time intervals, 7 days apart. Sixty-seven patients were included. Variability between centres was comparable at 48 h and 3 months interval but almost doubled at 9 months. The mean absolute difference in %FMD was 1.04, 0.99, and 1.45% at the three time intervals, respectively. Curves were generated to indicate the number of patients required for adequate power in crossover and parallel study designs. Conclusion This study demonstrates for the first time that in a multicentre setting reproducible FMD measurements can be achieved for short- and medium-term evaluation, which are comparable with those reported from specialized laboratories. These findings justify the use of FMD as an outcome measure for short- and medium-term assessment of pharmacological intervention

Maintaining a minimally invasive surgical service during a pandemic

PURPOSE: The safety of minimally invasive surgery (MIS) was questioned in the COVID-19 pandemic due to concern regarding disease spread. We continued MIS during the pandemic with appropriate protective measures. This study aims to assess the safety of MIS compared to Open Surgery (OS) in this setting. METHODS: Operations performed during 2020 lockdown were compared with operations from the same time-period in 2019 and 2021. Outcomes reviewed included all complications, respiratory complications, length of stay (LOS) and operating surgeon COVID-19 infections (OSI). RESULTS: In 2020, MIS comprised 52% of procedures. 29% of MIS 2020 had complications (2019: 24%, 2021: 15%; p = 0.08) vs 47% in OS 2020 (p = 0.04 vs MIS). 8.5% of MIS 2020 had respiratory complications (2019: 7.7%, 2021: 6.9%; p = 0.9) vs 10.5% in OS 2020 (p = 0.8 vs MIS). Median LOS[IQR] for MIS 2020 was 2.5[6] days vs 5[23] days in OS 2020 (p = 0.06). In 2020, 2 patients (1.2%) were COVID-19 positive (MIS: 1, OS: 1) and there were no OSI. CONCLUSION: Despite extensive use of MIS during the pandemic, there was no associated increase in respiratory or other complications, and no OSI. Our study suggests that, with appropriate protective measures, MIS can be performed safely despite high levels of COVID-19 in the population

Thoracoscopic vs open repair of congenital diaphragmatic hernia after extracorporeal membrane oxygenation: a comparison of intra-operative data

Purpose: ECMO is an escalation treatment for hypoxic respiratory failure in patients with CDH. Open repair has been advocated after ECMO indicating that physiological changes associated to thoracoscopic repair were not well tolerated. Methods: We have performed a retrospective review of all patients who underwent ECMO prior CDH repair over a 7 year period (2015–2021). Outcome measures were intra-operative Ph, PCO2, PO2 and FiO2 at 30 min, 1 h 30 min, and 2 h 30 min of surgery, operative time and recurrence rate. Data are shown in median (range). Results: Eleven patients required ECMO prior CDH repair. Six of eleven (55%) were done thoracoscopically (Group A) and five of eleven (45%) via laparotomy (Group B). Two of six (33%) patients (Group A) were converted to a laparotomy, one of six (16%) patient developed a recurrence, and there was no recurrence in Group B. Two of five (40%) patients died within the first 60 days of life, whilst there was no death in Group A. Intra-operative values are shown below. Conclusion: Whilst this is a preliminary report of a limited number of patients, there is no obvious difference of intra-operative blood gas parameters during surgical repair in patients after ECMO. Thoracoscopic CDH repair may be considered in patients after ECMO

Donor cell engineering with GSK3 inhibitor–loaded nanoparticles enhances engraftment after in utero transplantation

Host cell competition is a major barrier to engraftment after in utero hematopoietic cell transplantation (IUHCT). Here we describe a cell-engineering strategy using glycogen synthase kinase-3 (GSK3) inhibitor–loaded nanoparticles conjugated to the surface of donor hematopoietic cells to enhance their proliferation kinetics and ability to compete against their fetal host equivalents. With this approach, we achieved remarkable levels of stable, long-term hematopoietic engraftment for up to 24 weeks post-IUHCT. We also show that the salutary effects of the nanoparticle-released GSK3 inhibitor are specific to donor progenitor/stem cells and achieved by a pseudoautocrine mechanism. These results establish that IUHCT of hematopoietic cells decorated with GSK3 inhibitor–loaded nanoparticles can produce therapeutic levels of long-term engraftment and could therefore allow single-step prenatal treatment of congenital hematological disorders

Isolation of esophageal stem cells with potential for therapy.

Long-gap esophageal atresia represents a significant challenge for pediatric surgeons and current surgical approaches are associated with significant morbidity. A tissue-engineered esophagus, comprising cells seeded onto a scaffold, represents a therapeutic alternative. In this study, we aimed to determine the optimal techniques for isolation and culture of mouse esophageal epithelial cells and to isolate CD34-positive esophageal epithelial stem cells from cadaveric mouse specimens

Evaluation of short‐term safety of ultrasound‐guided foetal fluid sampling in the dog (Canis lupus familiaris)

Background: In humans, analysis of amniotic fluid is widely used for diagnostic and prognostic purposes. Amniocentesis has scarcely been used in veterinary medicine to date, despite a tremendous potential for clinical and research applications in dogs. Our study aimed to establish a safe method for foetal fluid sampling in female dogs. Methods: Two transabdominal ultrasound-guided methods were assessed: the "free hand" and the needle-guided bracket sampling. In addition, through a subsequent routinely scheduled ovariohysterectomy, fluid was directly collected. Samples from 98 conceptuses were collected at day 46.7 +/- 7.5 of pregnancy. Results: The amount of fluid retrieved varied between 0.5 and 5.0 ml per collection. Macroscopic examination of the uterus and conceptuses identified 53% of the puncture sites. Neither fluid leakage nor foetal injury was detected, and six hematomas (5.8%) were visible. Ultrasound-guided foetal fluid collection was found to be potentially safe, and it can be performed by using either transabdominal method. Conclusion: Foetal fluid collection is possible with relative ease and low short-term risk, and may open paths for diagnostic, therapeutic and research purposes in dogs. The procedure can provide new insights into prenatal clinical medicine, including diagnostics of foetal deaths, early identification of heritable diseases and so on