The utility of routine echocardiography in newborn infants with a persistent oxygen requirement

In the era of antenatal screening for congenital heart disease (CHD), infants presenting with an undiagnosed significant CHD are rare. However, term infants admitted with an initial diagnosis of TTN and a prolonged oxygen requirement often undergo an echocardiogram. We aimed to assess whether this practice yields any additional cases of undiagnosed CHD. We performed a retrospective chart review over a three year period [2013 ­ 2015] of term (> 36 weeks) infants admitted to the NICU for ≥ 5 days with a diagnosis of TTN and received an echocardiogram. The presence of CHD on the echocardiogram was assessed. Forty-seven infants were enrolled. The median age of echocardiogram was day four [2 ­ 8]. No infant had a diagnosis of significant CHD on the postnatal echocardiogram. A small muscular VSD was identified in two infants. Routine echocardiography for this cohort of infants to rule out major CHD appears to be unwarranted.

Evaluation of a novel waste anaesthetic gas scavenger device for use during recovery from anaesthesia.

Volatile anaesthetic agents are a potential occupational health hazard to theatre and recovery staff. Operating theatres and anaesthetic rooms are required to be equipped with scavenging systems, but recovery units often are not. We compared exhaled, spectrophotometric sevoflurane and desflurane concentrations 15 cm from the mouth ('patient breathing zone') and 91 cm laterally to the patient ('nurse work zone') in 120 patients after tracheal extubation who were consecutively allocated to either ISO-Gard mask oxygen/scavenging or standard oxygen mask, 0 min, 10 min and 20 min after arrival in the theatre recovery unit. Median (IQR [range]) duration of anaesthesia was similar between groups (control 76 (44-119 [15-484]) min vs. study group 90 (64-130 [15-390]) min, p = 0.136). Using the ISO-Gard mask, the 20-min mean patient breathing zone and nurse work zone exhaled anaesthetic levels were ~ 90% and 78% lower than those recorded in the control group, respectively, and were within the recommended 2 ppm maximum environmental exposure limit in the patient breathing zone of 53 out of 60 (88%) and the nurse work zone of all 60 (100%) patients on first measurement in the recovery room (vs. 10 out of 60 (17%) and 40 out of 60 (67%) in the control group). Our study indicates that the ISO-Gard oxygen/scavenging mask reduces the level of exhaled sevoflurane and desflurane below recommended maximum exposure limits near > 85% of extubated patients within ~ 20 s of application in the recovery unit after surgery. We encourage the use of this mask to minimise the occupational exposure of recovery staff to exhaled volatile agents.

Effectiveness of chemical pleurodesis in spontaneous pneumothorax recurrence prevention: a systematic review.

OBJECTIVES: Spontaneous pneumothorax is a common pathology. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second occurrence. This study comprehensively reviews the existing literature regarding chemical pleurodesis efficacy. DESIGN: We systematically reviewed the literature to identify relevant randomised controlled trials (RCTs), case-control studies and case series. We described the findings of these studies and tabulated relative recurrence rates or ORs (in studies with control groups). Meta-analysis was not performed due to substantial clinical heterogeneity. RESULTS: Of 560 abstracts identified by our search strategy, 50 were included in our systematic review following screening. Recurrence rates in patients with chest tube drainage only were between 26.1% and 50.1%. Thoracoscopic talc poudrage (four studies (n=249)) provided recurrence rates of between 2.5% and 10.2% with the only RCT suggesting an OR of 0.10 compared with drainage alone. In comparison, talc administration during video-assisted thoracic surgery (VATS) from eight studies (n=2324) recurrence was between 0.0% and 3.2%, but the RCT did not demonstrate a significant difference compared with bleb/bullectomy alone. Minocycline appears similarly effective post-VATS (recurrence rates 0.0-2.9%). Prolonged air leak and recurrence prevention using tetracycline via chest drain (n=726) is likely to provide recurrence rates between 13.0% and 33.3% and autologous blood patch pleurodesis (n=270) between 15.6% and 18.2%. CONCLUSIONS: Chemical pleurodesis postsurgical treatment or via thoracoscopy appears to be most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised trials or other comparative studies.

Pediatric penile reconstruction using autologous split-thickness skin graft.

This video provides a case report of penis entrapment secondary to excessive skin removal during circumcision. It highlights the technical aspects of pediatric penile reconstruction using autologous split-thickness skin graft (STSG). Key points include: 1. Infection prevention is paramount and antibiotic prophylaxis is routine. 2. The usual harvest site for the STSG is the lateral thigh because of its source of glabrous skin and convenient proximity to the penis. The lateral thigh is also outside of the diapered area, which helps lessen postoperative pain and infectious risks. 3. A dermatome is used to harvest the STSG. Skin thickness for penis coverage at this age is usually 10-12/1000 of an inch. 4. Direct contact of the graft and wound bed is essential for graft uptake. Hemostasis of the wound bed is critical to prevent hematoma formation. Elimination of redundant tissue is also important to ensure maximal contact between the graft and underlying wound bed. 5. A pressure dressing or bolster is used to prevent shear, and provide contact between the graft and wound bed for at least the first 5 days. 6. A semi-occlusive dressing, Tegaderm, was used on the donor site and it is believed that it provides a moist environment conducive for epithelial and dermal healing. 7. Lymphedema can result if excess distal penile skin is not excised. It is prudent to limit the amount of mucosal collar or consider direct anastomosis to the glans.

Role of CT in assessing pleural malignancy prior to thoracoscopy.

The definitive diagnosis of pleural malignancy depends upon histological confirmation by pleural biopsy. CT is reported to have a high sensitivity and specificity for the diagnosis of malignant pleural disease, and is part of the routine diagnostic workup of these patients. The aim of this study was to assess the sensitivity and specificity of CT in detecting pleural malignancy prior to definitive histology obtained via thoracoscopy in a large cohort of patients with suspected malignant pleural disease. Retrospective review of thoracoscopies between January 2008 and January 2013 at two UK tertiary referral centres: Oxford and Preston. The histological results were compared with the CT reported diagnosis before the procedure. CT scan reports were assessed by independent respiratory physicians as to whether the radiologist concluded evidence of malignant pleural disease or benign features only. 211 (57%) of 370 patients included in the analysis had malignant disease: CT scans were reported as 'malignant' in 144, giving a sensitivity of 68% (95% CI 62% to 75%). Of the 159 patients with benign disease, 124 had CT scans reported as benign: specificity 78% (72% to 84%). The positive predictive value of a malignant CT report was 80% (75% to 86%), with a negative predictive value of 65% (58% to 72%). A significant proportion of patients being investigated for malignant disease will have malignancy despite a negative CT report. The use of CT alone in determining which patients should have invasive pleural biopsies should be re-evaluated, and further studies to define the diagnostic pathway are now required.

A UK hospital based multidisciplinary balance clinic run by allied health professionals: first year results.

OBJECTIVE: To describe our experience of a new multidisciplinary balance clinic for the management of patients with vestibular disorders, run as a pilot project for 12 months. DESIGN: Retrospective review of the outcomes of 194 patients. SUBJECTS: All patients were first evaluated at the balance assessment clinic. Subsequently, each case was discussed at the multidisciplinary balance clinic weekly review meeting, and management decisions made. RESULTS: The mean waiting time for the balance assessment clinic was 12 weeks (standard deviation six weeks). In total, 74 per cent of patients underwent rehabilitation, 26 per cent were seen in the balance specialist clinic, 15 per cent underwent additional testing, 6 per cent were followed up in adult otology clinics and one patient was listed for surgery. The waiting time for vestibular rehabilitation was reduced from 21 to 15 weeks. Patient satisfaction with the service was encouraging, and no adverse outcomes were recorded. CONCLUSION: This multidisciplinary balance clinic, run by allied health professionals, represents an alternative model for the management of patients with balance disorders.

ICOS is critical for T helper cell-mediated lung mucosal inflammatory responses.

We examined the requirement for and cooperation between CD28 and inducible costimulator (ICOS) in effective T helper (TH) cell responses in vivo. We found that both CD28 and ICOS were critical in determining the outcome of an immune response; cytolytic T lymphocyte-associated antigen 4-immunoglobulin (CTLA-4-Ig), ICOS-Ig and/or a neutralizing ICOS monoclonal antibody attenuated T cell expansion, TH2 cytokine production and eosinophilic inflammation. CD28-dependent signaling was essential during priming, whereas ICOS-B7RP-1 regulated TH effector responses, and the up-regulation of chemokine receptors that determine T cell migration. Our data suggests a scenario whereby both molecules regulate the outcome of the immune response but play separate key roles: CD28 primes T cells and ICOS regulates effector responses.

Cloning, expression, and function of BLAME, a novel member of the CD2 family.

The CD2 family is a growing family of Ig domain-containing cell surface proteins involved in lymphocyte activation. Here we describe the cloning and expression analysis of a novel member of this family, B lymphocyte activator macrophage expressed (BLAME). BLAME shares the structural features of the CD2 family containing an IgV and IgC2 domain and clusters with the other family members on chromosome 1q21. Quantitative PCR and Northern blot analysis show BLAME to be expressed in lymphoid tissue and, more specifically, in some populations of professional APCs, activated monocytes, and DCS: Retroviral forced expression of BLAME in hematopoietic cells of transplanted mice showed an increase in B1 cells in the peripheral blood, spleen, lymph nodes, and, most strikingly, in the peritoneal cavity. These cells do not express CD5 and are CD23(low)Mac1(low), characteristics of the B1b subset. BLAME may therefore play a role in B lineage commitment and/or modulation of signal through the B cell receptor.

A role for chromosomal instability in the development of and selection for radioresistant cell variants.

Chromosome instability is a common occurrence in tumour cells. We examined the hypothesis that the elevated rate of mutation formation in unstable cells can lead to the development of clones of cells that are resistant to the cancer therapy. To test this hypothesis, we compared chromosome instability to radiation sensitivity in 30 independently isolated clones of GM10115 human-hamster hybrid cells. There was a broader distribution of radiosensitivity and a higher mean SF(2)in chromosomally unstable clones. Cytogenetic and DNA double-strand break rejoining assays suggest that sensitivity was a function of DNA repair efficiency. In the unstable population, the more radioresistant clones also had significantly lower plating efficiencies. These observations suggest that chromosome instability in GM10115 cells can lead to the development of cell variants that are more resistant to radiation. In addition, these results suggest that the process of chromosome breakage and recombination that accompanies chromosome instability might provide some selective pressure for more radioresistant variants.

Cutting edge: the related molecules CD28 and inducible costimulator deliver both unique and complementary signals required for optimal T cell activation.

Optimal T cell activation requires engagement of CD28 with its counterligands B7-1 and B7-2. Inducible costimulator (ICOS) is the third member of the CD28/CTLA4 family that binds a B7-like protein, B7RP-1. Administration of ICOS-Ig attenuates T cell expansion following superantigen (SAg) administration, but fails to regulate either peripheral deletion or anergy induction. ICOS-Ig, but not CTLA4-Ig, uniquely regulates SAg-induced TNF-alpha production, whereas IL-2 secretion is modulated by CTLA4-Ig, but not ICOS-Ig. In contrast, both ICOS and CD28 are required for complete attenuation of IL-4 production. Our data suggest that ICOS and CD28 regulate T cell expansion and that ligation of either CD28 or ICOS can either uniquely regulate cytokine production (IL-2/TNF-alpha) or synergize for optimal cytokine production (IL-4) after SAg administration.

Tissue expansion in head and neck burn reconstruction.

The advent of tissue expansion has provided a useful tool for the reconstructive burn surgeon. As with many new techniques, there was an initial wave of enthusiasm surrounding the introduction of tissue expansion to burn reconstruction in the 1980s. High complication rates and many dissatisfying results followed. After early widespread use of tissue expansion, the authors have settled on a more refined approach to the reconstruction of head, neck, and facial burns. Today, head and neck burn reconstruction is accomplished best with a combination of skin grafting, local flaps, and occasional free flaps in addition to tissue expansion. In carefully selected head and neck burn patients and in many burn alopecia patients, tissue expansion can provide excellent functional and aesthetic results, with minimal donor site morbidity.

Genomic instability induced by high and low LET ionizing radiation.

Genomic instability is the increased rate of acquisition of alterations in the mammalian genome, and includes such diverse biological endpoints as chromosomal destabilization, aneuploidy, micronucleus formation, sister chromatid exchange, gene mutation and amplification, variations in colony size, reduced plating efficiency, and cellular transformation. Because these multiple endpoints persist long after initial radiation exposure, genomic instability has been proposed to operate as a driving force contributing to genetic plasticity and carcinogenic potential. Many of these radiation-induced endpoints depend qualitatively and quantitatively on genetic background, dose and LET. Differences in the frequency and temporal expression of chromosomal instability depend on all three of the foregoing factors. On the other hand, many of these endpoints appear independent of dose and show bystander effects, implicating non-nuclear targets and epigenetic regulatory mechanisms. The present work will survey results concerning the LET dependence of genomic instability and the role of epigenetic mechanisms, with a particular emphasis on the endpoint of chromosomal instability.

Critical target and dose and dose-rate responses for the induction of chromosomal instability by ionizing radiation.

To investigate the critical target, dose response and dose-rate response for the induction of chromosomal instability by ionizing radiation, bromodeoxyuridine (BrdU)-substituted and unsubstituted GM10115 cells were exposed to a range of doses (0.1-10 Gy) and different dose rates (0.092-17.45 Gy min(-1)). The status of chromosomal stability was determined by fluorescence in situ hybridization approximately 20 generations after irradiation in clonal populations derived from single progenitor cells surviving acute exposure. Overall, nearly 700 individual clones representing over 140,000 metaphases were analyzed. In cells unsubstituted with BrdU, a dose response was found, where the probability of observing delayed chromosomal instability in any given clone was 3% per gray of X rays. For cells substituted with 25-66% BrdU, however, a dose response was observed only at low doses (<1.0 Gy); at higher doses (>1.0 Gy), the incidence of chromosomal instability leveled off. There was an increase in the frequency and complexity of chromosomal instability per unit dose compared to cells unsubstituted with BrdU. The frequency of chromosomal instability appeared to saturate around approximately 30%, an effect which occurred at much lower doses in the presence of BrdU. Changing the gamma-ray dose rate by a factor of 190 (0.092 to 17.45 Gy min(-1)) produced no significant differences in the frequency of chromosomal instability. The enhancement of chromosomal instability promoted by the presence of the BrdU argues that DNA comprises at least one of the critical targets important for the induction of this end point of genomic instability.

What are the molecular mechanisms of neural tube defects?

Neural tube defects (NTDs) are some of the most common human malformations. The vast majority of NTDs can be prevented by the administration of folic acid; however, to date there has been no effective treatment of folic acid-resistant NTDs. A recent paper has confirmed an earlier report that the administration of inositol to the curly tail mutant mouse, which is a model of folate-resistant NTDs, can cure such defects. The molecular pathway by which this is achieved is thought to occur by the up-regulation of the retinoic acid receptor beta in the underlying hindgut endoderm, correcting a proliferation defect. However, alternative explanations also may account for NTDs.

Lyso-phosphatidylcholine and outcome of preterm babies with respiratory distress syndrome treated with surfactant.

Phosphatidylcholine (PC) is the predominant phospholipid in natural surfactant preparations. A metabolic intermediate, lyso-PC, is potentially injurious to the lungs. In the present study, tracheal aspirates from preterm babies with respiratory distress syndrome treated with surfactant were examined for the presence of lyso-PC to determine if there was any correlation with outcome. Eighteen babies were assigned to receive initially either 100 or 200 mg/kg Curosurf followed by up to three further 100-mg/kg doses if required. Lyso-PC was present in aspirates taken 12-24 h after the last treatment from nine of 11 infants who initially received 200 mg/kg but in only one from seven receiving 100 mg/kg initially, and was dependent on the total dose of phospholipid administered. Three babies in the low-dose group developed bronchopulmonary dysplasia, whereas two in the high-dose group were non-survivors, however we could not correlate the presence of lyso-PC with adverse long-term outcome in this group of preterm infants.

Distraction osteogenesis of costochondral neomandibles: a clinical experience.

Distraction osteogenesis quickly has become a mainstay in the treatment of craniofacial syndromes with mandibular hypoplasia. We report on a series of eight patients undergoing distraction osteogenesis of neomandibles constructed with costochondral grafts. The length of distraction, resting phase between distraction and device removal, and complication rate were significantly greater in the rib-graft distraction group when compared with our series of native mandibular distraction patients (n = 21 devices). Most complications were minor, including pintrack infection and hardware failure; however, major complications included fibrous union and facial nerve praxia. Secondary procedures have been able to be performed successfully on previously distracted rib grafts as well.