Ex utero intrapartum treatment with extracorporeal membrane oxygenation for severe congenital diaphragmatic hernia

Purpose

The purpose of this study was to determine whether ex utero intrapartum treatment with extracorporeal membrane oxygenation (EXIT to ECMO) is a reasonable approach for managing patients antenatally diagnosed with severe congenital diaphragmatic hernia (CDH).

Methods

A 6-year retrospective review was performed on fetuses with severe CDH (liver herniation and a lung/head ratio <1.4, percentage of predicted lung volume <15, and/or congenital heart disease). Fourteen of the patients underwent EXIT with a trial of ventilation. Fetuses with poor preductal oxygen saturations despite mechanical ventilation received ECMO before their delivery. Maternal-fetal outcomes were analyzed.

Results

There were no maternal-reported complications. Three babies passed the ventilation trial and survived, but 2 of them required ECMO within 48 hours. The remaining 11 fetuses received ECMO before their delivery. Overall survival after EXIT-to-ECMO was 64%. At 1-year follow-up, all survivors had weaned off supplemental oxygen, but 57% required diuretics and/or bronchodilators.

Conclusion

This is the largest reported experience using EXIT to ECMO in the management of severe CDH. The EXIT-to-ECMO procedure is associated with favorable survival rates and acceptable pulmonary morbidity in fetuses expected to have a poor prognosis under conventional management.     

Cytokine Response to Ischemia/Reperfusion Injury in an Ex Vivo Perfused Porcine Liver Model

Background

We evaluated the degree of inflammatory response after ischemia/reperfusion injury by an extracorporeal normothermic autologous hemoperfusion of porcine livers.

Materials and Methods

Livers explanted from 7 pigs were perfused extracorporeally at 39°C with autologous blood. Serum samples were obtained hourly until 6 hours from the beginning of reperfusion and assayed for 9 different cytokines.

Results

Significant elevations in interleukin 6 (IL-6) and IL-8 were noted following reperfusion (P < .001), with both demonstrating an increase which followed a sigmoid curve; other cytokines that were assessed showed no significant change.

Conclusions

The ex vivo model excludes the liver from the influence of external systemic factors such as hormones, the autonomic nervous system, and other regulatory molecules produced elsewhere in the body, allowing the response to the ischemia/reperfusion injury to be studied in isolation and in considerable detail. Although this study examined a relatively short period, the increases in only IL-6 and IL-8 suggested that these are important molecules in the early phase after reperfusion.     

Influence of interleukin-6 promoter polymorphism -174 g/c on kidney graft outcome

Background

The cytokine interleukin-6 (IL-6) is important in both immune responses and cardiovascular diseases. The IL-6 promoter polymorphism −174 G/C is associated with increased plasma concentrations of IL-6. The relationship between IL-6 polymorphisms and graft survival, cardiovascular events, and new-onset diabetes mellitus after kidney transplantation is controversial.

Objective

To analyze whether IL-6 (−174 G/C) polymorphism influences kidney graft survival or development of chronic allograft nephropathy, cardiovascular events, or new- onset diabetes.

Methods

The IL-6 promoter polymorphism (−174 G/C) was analyzed using the polymerase chain reaction with sequence-specific primers in 335 kidney transplant recipients. Data for graft survival, chronic graft nephropathy, cardiovascular events, and new-onset diabetes were obtained retrospectively from clinical records. Categorical variables were compared between individuals with CC, GG, and GC genotypes using χ² tests. Survival analysis was performed using the Kaplan-Meier method, comparing groups using the log-rank test.

Results

No significant differences were observed in 5-year graft survival between individuals with CC and GC/GG genotypes (85.3% vs 77.1%; P = .22). Nor were significant differences noted in the rates of chronic allograft nephropathy (37.5% vs 33.8%; P = .48), cardiovascular events (10.0% vs 23.0%; P = .10), or new-onset diabetes (7.5% vs 11.8%; P = .28).

Conclusion

There is no association between IL-6 (−174 G/C) polymorphism and graft survival or development of chronic allograft nephropathy, cardiovascular events, or new- onset diabetes.     

Medical students' knowledge about organ transplantation: a South African perspective

Background

Educating physicians about transplantation during undergraduate training can improve organ procurement rates. The aim of this study was to evaluate and analyze the knowledge of medical students regarding transplantation.

Methods

A previously validated self-administered anonymous questionnaire was distributed to all medical students.

Results

Of the 346 participants, 217 (63%) were preclinical students. Their mean age was 21 years (range, 18-33) and 62% were women. Twenty-nine (8%) students were registered as organ donors. One third of all study participants received formal transplantation teaching; a greater proportion of clinical students received teaching compared with the preclinical group (52% vs 22%, P < .05). Knowledge was frequently reported for kidney (88%), liver (81%), bone marrow (78%), and heart (76%) transplantation. Small Intestine (13%), pancreas (9%), and pancreatic islets (4%) were the least recognized organs/tissues. Ninety-six percent and 62% of respondents were aware of kidney and liver living-donor transplants, respectively; the 27% of students with an interest in a surgical career had better knowledge of living-donor transplantation (P < .05). Only 22 (6%) students knew which solid organ transplants were performed in South Africa.

Conclusion

Medical students have limited knowledge about organ transplantation; there is a need for educational intervention early in the medical curriculum.     

Adrenal cortical cell transplantation

Purpose

The adrenal cortex is a critical component of the hypothalamic-pituitary-adrenal/gonadal axis that coordinates the stress response and maintains homeostasis. The authors hypothesize that adrenal cortical cells can be transplanted in adrenal insufficiency states to regenerate the adrenal cortex.

Methods

Murine adrenal glands were dissociated into adrenal cortical cells. Cells cultured in a collagen matrix were transplanted under the renal capsule. The implants were retrieved 1, 2, 4, and 8 weeks later. Total RNA was extracted from the retrieved specimens and was analyzed by real-time polymerase chain reaction.

Results

All animals survived the surgical procedure. At implant retrieval, a distinct organoid could be visualized under the renal capsule. The expressions of adrenal-specific markers including Sf1, Dax1, Star, Cyp11a, Cyp11b1, and Cyp21 were detectable in the retrieved specimens up to 8 weeks posttransplantation.

Conclusion

Primary adrenal cortical cells retained their gene expressions after heterotopic transplantation. Ex vivo gene transfer followed by adrenal cortical cell transplantation may lead to curative therapy for patients with adrenal insufficiency.     

Recombinant Human Erythropoietin Pretreatment Attenuates Heart Ischemia-Reperfusion Injury in Rats by Suppressing the Systemic Inflammatory Response

Background

Ischemia-reperfusion (I/R) injury may influence graft function after transplantation. Erythropoietin (EPO) attenuates I/R injury in various animal organs such as intestine, brain, and kidney.

Objective

To evaluate the effects of pretreatment with recombinant human EPO (rhEPO) on I/R-induced heart injury.

Materials and Methods

A rat model of I/R injury was established by ligating the left descending coronary artery for 30 minutes, followed by reperfusion for 4 hours. Fifty Sprague-Dawley rats were divided into 5 groups: sham operation; I/R; I/R+rhEPO, 100 U/kg; I/R+rhEPO, 1000 U/kg; and I/R+rhEPO, 5000 U/kg. Electrocardiograms were assessed continuously to note arrhythmia caused by reperfusion. Serum concentrations of interleukin (IL)-6 and IL-8, and tumor necrosis factor-α were measured at 2 and 4 hours after reperfusion.

Results

The rhEPO-treated animals exhibited dosage-dependent significant reduction in the incidence of ventricular arrhythmia caused by reperfusion, and markedly decreased serum concentrations of IL-6, IL-8, and tumor necrosis factor-α (P < .05) compared with the I/R group (P < .05).

Conclusion

The rhEPO attenuates myocardial I/R injury in rats, at least in part related to inhibition of the system inflammatory response.     

Thoracoscopy in pediatric pleural empyema: a prospective study of prognostic factors

Purpose

The indications for thoracoscopy remain imprecise in cases of pleural empyema. This study aimed to identify preoperative prognostic factors to help in the surgical decision.

Methods

From 1996 to 2004, 50 children with parapneumonic pleural empyema underwent thoracoscopy either as the initial procedure (n = 26) or after failure of medical treatment (n = 24). Using multivariate analysis, we tested the prognostic value of clinical and bacteriological data, the ultrasonographic staging of empyema, and the delay before surgery. Outcome measures were technical difficulties, postoperative complications, time to apyrexia, duration of drainage, and length of hospitalization.

Results

The clinical and bacterial data did not significantly predict the postoperative course. Echogenicity and the presence of pleural loculations at ultrasonography were not independent significant prognostic factors. A delay between diagnosis and surgery of more than 4 days was significantly correlated (P < .05) with more frequent surgical difficulties, longer operative time, more postoperative fever, longer drainage time, longer hospitalization, and more postoperative complications, such as bronchopleural fistula, empyema relapse, and persistent atelectasia.

Conclusion

The main prognostic factor for thoracoscopic treatment of pleural empyema is the interval between diagnosis and surgery. A 4-day limit, corresponding to the natural process of empyema organization, is significant. The assessment of loculations by ultrasonography alone is not sufficient to predict the postoperative course.     

Effects of Inhaled Nitric Oxide on Primary Graft Dysfunction in Lung Transplantation

Introduction and Objectives

Inhaled nitric oxide (iNO) is a gaseous drug with known properties of specific pulmonary vasodilation and improved oxygenation. In some clinical trials on lung transplantation (LT) in animals, it has been demonstrated to reduce primary graft dysfunction (PGD) by limiting neutrophil adhesion and the inflammatory cascade. Our objective was to assess whether iNO showed this immunomodulatory effect by determining interleukin (IL)-6, -8, and -10 levels in blood and bronchoalveolar lavage (BAL) in LT patients, and its relationship with PGD incidence.

Materials and Methods

Forty-nine LT patients were recruited and included in the iNO or in the control group. Patients in the first group were given iNO (10 ppm) from the start of LT to 48 hours afterward. BAL and blood samples were taken preimplantation and at 12, 24, and 48 hours after graft reperfusion.

Results

The iNO group displayed a significantly lower incidence (P < .035) of PGD (17.2%) than the control group (45%). Significant differences (P < .05) were also observed in the iNO group with lower levels of IL-6 (in blood at 12 hours), IL-8 (in blood and BAL at 12 and 24 hours), and IL-10 (in blood at 12 and 24 hours and BAL at 24 hours).

Conclusions

PGD is associated with the development of an inflammatory process that is reduced by giving iNO to lung recipients. In our series, the iNO group displayed significantly lower content of IL-6, IL-8, and IL-10 in the majority of samples at 12 and 24 hours compared with the control group.     

Impact of antibiotic therapy on laboratory analysis of parapneumonic pleural fluid in children

Objective

The therapeutic management of parapneumonic pleural effusions (PPE) is controversial in children. Decision-making often relies on parameters such as gross appearance of pleural fluid and on bacteriologic and biochemical analyses. Our goal was to describe the laboratory profile of PPE in children and to assess the influence of previous administration of antibacterial agents on culture and biochemical results.

Patients and methods

This was a prospective study including children (age, 1 month to 16 years) with a diagnosis of PPE. Two groups were evaluated: children with or without antibiotic treatment up to 48 hours before analysis of pleural fluid. Results were analyzed using the χ² or Mann-Whitney test (α = .05). Odds ratio and 95% confidence intervals (95% CIs) were calculated, with control of previous antibiotic therapy using multivariate logistic regression analysis, to determine the risk of empyema associated with specific biochemical parameters.

Results

One hundred ten children were selected. Fifty percent had received antibiotics at least 48 hours before pleural fluid analysis. Differences were observed between the groups in terms of PPE gross appearance (P = .033) and identification of bacteriologic agent by culture or Gram stain (P = .023). Biochemical parameters (pH ≤7.1 and glucose ≤40 mg/dL) were associated with increased odds of receiving a more invasive treatment. For pH, the odds ratio was 9.614 (95% CI, 1.952-47.362; P = .005); and for glucose, 9.201 (95% CI, 1.333-63.496; P = .024).

Conclusions

Previous use of antibacterial agents affected the bacteriologic analysis of pleural fluid in this pediatric sample admitted for PPE. However, it did not interfere significantly with biochemical parameters of pleural fluid.     

European Quality System for Tissue Banking

Aim

The aims of this project were to analyze the factors that influence quality and safety of tissues for transplantation and to develop the method to ensure standards of quality and safety in relation to tissue banking as demanded by European Directive 2004/23/EC and its technical annexes. It is organized in 4 Working Groups, the objectives of each one being focused in a specific area.

Standards

The Guide of Recommendations for Tissue Banking is structured into 4 parts: (1) quality systems that apply to tissue banking and general quality system requirements, (2) regulatory framework in Europe, (3) standards available, and (4) recommendations of the fundamental quality and safety keypoints.

Registry

This Working Group handled design of a multinational musculoskeletal tissue registry prototype.

Training

This Working Group handled design and validation of a specialized training model structured into online and face-to-face courses. The model was improved with suggestions from students, and 100% certification was obtained.

Audit

The Guide for Auditing Tissue Establishments provides guidance for auditors, a self-assessment questionnaire, and an audit report form. The effectiveness and sustainability of the outputs were assessed. Both guides are useful for experienced tissue establishments and auditors and also for professionals that are starting in the field. The registry prototype proves it is possible to exchange tissues between establishments throughout Europe. The training model has been effective in educating staff and means having professionals with excellent expertise. Member states could adapt/adopt it. The guides should be updated periodically and perhaps a European organization should take responsibility for this and even create a body of auditors.     

A Novel Predictive Method for Assessing the Quality of Isolated Pancreatic Islets Using Scanning Electrochemical Microscopy

Introduction

The current methods for evaluating islet potency are not useful in clinical transplantation. Therefore, we need reliable, rapid methods enabling accurate prediction of islet quality.

Materials and Methods

We evaluated respiratory activity using scanning electrochemical microscopy (SECM), glucose-stimulated respiratory activity, glucose-stimulated insulin release, ADP/ATP assays, insulin/DNA levels, and Trypan blue exclusion tests as predictive methods for the ability of isolated rat islets to cure syngeneic diabetic rats.

Results

Although glucose-stimulated respiratory activity, basal respiratory activity, ADP/ATP ratio, and glucose-stimulated insulin release were significantly correlated with the outcome of transplantation into diabetic rats, there was no correlation between outcomes, insulin/DNA ratios, and Trypan blue exclusion tests. The glucose-stimulated respiratory activity in islet preparations that could cure diabetic rats was significantly greater than those unable to cure diabetes. Rat islets with >1.5-fold glucose-stimulated respiratory activity consistently cured diabetic rats, whereas those with a value <1.5 hardly cured any rats.

Conclusion

Measurement of the glucose-stimulated respiratory activity using SECM technique is a novel method that may be useful as a rapid, potent predictor of the outcome of clinical islet transplantation.     

Hepatolithiasis after hepatic portoenterostomy for biliary atresia

Background

Hepatolithiasis after hepatic portoenterostomy for biliary atresia has been paid little attention, with only 22 reported cases.

Patients and Methods

Fifteen patients underwent living-related liver transplantation for biliary atresia after hepatic portoenterostomy in our hospital between 1998 and 2004. The resected livers were examined for the existence and location of hepatolithiasis, composition of the calculi, and bacterial infection of bile. The relation between a history of cholangitis and the presence of hepatolithiasis was analyzed.

Results

Intrahepatic calculi were found in 8 (53%) of 15 patients. The calculi consisted of almost 100% calcium bilirubinate. Calculi were found in bile lakes in 8 patients. Bacteria were present in the bile in 8 (53%) of the 15 patients. Of the 8 patients, 7 (88%) had a history of ascending cholangitis.

Conclusions

Hepatolithiasis occurs after hepatic portoenterostomy for biliary atresia more frequently than previously thought. Bile stasis and possibly bile infection are the main causes of calculi formation.     

Thoracoscopic evacuation of retained posttraumatic hemothorax

Background

Residual posttraumatic hemothoraces occur in 1% to 20% of patients managed with tube thoracostomy. Video-assisted thoracoscopic surgery (VATS) has emerged as an alternative to thoracotomy to evacuate these retained collections. This report reviews a recent trauma unit experience with thoracoscopic evacuation of hemothoraces.

Methods

The records of all trauma patients undergoing surgical intervention for retained hemothoraces over the 30-month period January 2001 to June 2003 were reviewed.

Results

The study included 46 patients. All sustained penetrating injuries, 40 with stab and 6 with gunshot wounds. Twenty-two, 17, and 7 patients each had one, two and three attempts at drainage with tube thoracostomy, respectively. In 37 patients (80%), retained infected/uninfected pleural fluid was successfully evacuated thoracoscopically. VATS failed in 9 (20%) patients and the procedure was converted to open thoracotomy. Dense adhesions were present in all 9 of these patients. The mean time interval between injury and thoracoscopy and thoracotomy, was 13.3 days (range 3-46 days) and 14.5 days (range 11-24 days), respectively. The mean volume of pleural fluid evacuated thoracoscopically was 650 mL. The failure of VATS evacuation correlated with the empyema rate. The median postoperative stay was 5 days for both groups.

Conclusions

Video-assisted thoracoscopic surgery is an accurate, safe, and reliable operative therapy for retained posttraumatic pleural collections, even in patients presenting later than the conventionally accepted 3- to 5-day window from the time of injury.     

Gastric malignancies in breast cancer survivors: Pathology and outcomes

Background

As the number of breast cancer survivors increases, the appearance of second malignancies and unusual metastatic patterns likely also is increasing. In particular, we and others have observed gastric malignancies in breast cancer survivors.

Methods

We reviewed 3 regional hospital system tumor databases, comprising 19,049 analytic breast cancer cases, to determine the number, types, and outcomes of subsequent gastric malignancies.

Results

Twenty-eight patients developed subsequent gastric malignancies, representing .15% of breast cancer survivors; 82% of patients had gastric symptoms. Overall survival for the cohort was 39%. Twenty-four patients (86%) had gastric primaries and 13 died of their second cancers. Four patients had gastric metastases; all had lobular histology in both their primary tumors and metastatic lesions. Five patients had gastrointestinal stromal tumors; all patients underwent resection and currently are alive.

Conclusion

Gastric symptoms in breast cancer survivors may represent malignant lesions, often second primaries. All gastric metastases in our series were of lobular histology.     

Marked increase in incidence of Achromobacter xylosoxidans infections caused by sporadic acquisition from the environment

Background

An increased incidence of Achromobacter xylosoxidans infections has been observed at the Cystic Fibrosis Centre at Aarhus University Hospital, as the proportion of patients colonised with A. xylosoxidans increased from 6 to 10% from 2005 to 2009.

Methods

Pulsed field gel electrophoresis (PFGE) was used to type isolates of A. xylosoxidans.

Results

Four patients infected for 2-7 years were part of a larger epidemic spread involving both Danish CF centres, while 11 patients carried strains with unique genotypes. Longitudinal analysis of isolates from ten patients with multiple preserved isolates showed that each patient persistently carried isolates of a single genotype. Following lung transplantation, two patients showed re-colonisation of the lung grafts with the pre-transplant A. xylosoxidans strain.

Conclusions

A. xylosoxidans has been transmitted between patients from our clinic, but the recent increase in incidence is not caused by cross infections.     

Mitigation of Cytokine Storm by Intraoperative Use of Renal Replacement Therapy During Combined Liver-Kidney Transplantation

Background

Combined liver-kidney transplantation (CLKT) is a widely used multiorgan transplantation with good graft survival rates. Previous studies have shown beneficial effects of renal replacement therapy in critically ill patients. This observation led us to use intraoperative continuous veno-venous hemofiltration (CVVH) during multiorgan transplantations.

Methods

We analyzed (CRP) inflammatory response parameters of tumor necrosis factor (TNF)α, interleukin(IL)-6, procalcitonin (PCT) and C-reactive protein (CRP) at various stages of the combined transplantations.

Results

All patients survived with well-functioning grafts. Mean ± SD follow-up was 32.8 ± 14.2 months. During the whole operation we used intraoperative CVVH starting at the beginning and continuing in the intensive care unit (ICU) afterward (mean ± SD, 11.2 ± 8.4 hours). Intraoperative TNFα, IL-6, CRP, and PCT were measured before surgery, during hepatectomy in the anhepatic phase, before and after liver reperfusion, exactly before kidney reperfusion, after kidney reperfusion, and upon arrival in the ICU. The wash-out of cytokines together with hemodynamic stability gave optimal circumstances for recovery of the transplanted organs.

Conclusions

CVVH-based therapy offered stable intraoperative parameters, prevention of fluid overload, correction of metabolic disturbances, and wash-out of cytokines, which gave optimal circumstances for recovery of transplanted organs.