Prognostic tools for hypertrophic scar formation based on fundamental differences in systemic immunity

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP‐1, IL‐8, IL‐18 and IL‐23 levels have a strong correlation with HS (P < .010‐0.004; AUC = 0.790‐0.883). Notably, combinations of two or three cytokines (TNF‐a, MCP‐1 and IL‐23; AUC: 0.942, Nagelkerke R²: 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.     

Research on medication use in the neonatal intensive care unit

Introduction: Research on medication use aims at assessing how much of current pharmacotherapy is rational. In neonates, this is hampered by extensive off-label drug use and limited knowledge.

Areas covered: We report on medication use research and have conducted a systematic review of observational studies on medication use to provide an updated overview on characteristics, objectives, methods, and patterns in hospitalized neonates. Moreover, a review on aspects of medication use for opioids, anti-epileptics, gastric acid-related disorders and respiratory stimulants with emphasis on trends and impact of interventions is presented, illustrating how research on medication use can contribute to improved neonatal pharmacotherapy and more focused research. Medication use reports describe patterns and provide signals on irrational use, benchmarking, or can guide research priorities. Moreover, this may generate information on how neonatal health topics and their pharmacotherapy are handled over time or across regions.

Expert opinion: Research on medicine utilization is relevant, since it will inform us on aspects like trends, variability, or about the impact and pattern of implementation of guidelines in neonates. Further progress necessitates to merge datasets on medication use with clinical characteristics, and perinatal drug use remains an area in need of additional research.     

Diagnostic accuracy of lower extremity X-ray interpretation by 'specialized' emergency nurses.

OBJECTIVES: In the quest for a cost-effective and quality-preserving solution to manage crowding in the emergency department, the possibility of deploying regular emergency nurses for the treatment of acute ankle injuries was investigated. The aim of this study is to compare the diagnostic accuracy of emergency nurses with that of senior house officers in interpreting ankle and foot radiographs. METHODS: A prospective study comparing the assessment of 60 radiographs (30 feet and 30 ankles) by 16 emergency nurses before and after an educational session was performed. Each subset of 30 radiographs contained 12 fractures, hand-picked by a radiologist to represent everyday traumatology in the emergency department. The control group consisted of eight senior house officers representing everyday expertise. The outcome of the diagnostic assessment, represented as the pooled sensitivity and specificity for both groups, was compared using Z-statistics. RESULTS: Before the training session, the specialized emergency nurse group showed a sensitivity of 0.87 (confidence interval 0.83-0.91) compared with 0.93 (confidence interval 0.88-0.96) for the control group (P = 0.05). The specificity of specialized emergency nurses was 0.87 (confidence interval 0.81-0.92) compared with 0.93 (confidence interval 0.89-0.95) for the senior house officers (P < 0.05). After the training session, specialized emergency nurse diagnostic parameters did not differ significantly from the control group, displaying a sensitivity of 0.89 (confidence interval 0.86-0.92) and specificity of 0.92 (confidence interval 0.87-0.95). CONCLUSION: Before the training session, the specialized emergency nurse group showed a significantly lower accuracy than the SHO group. After training, however, the diagnostic accuracy did not differ significantly between groups. Therefore, we conclude that emergency nurses are able to accurately interpret foot and ankle radiographs after a short educational session.     

Delayed and persistent suppression of bronchoconstriction by trypsin in the airway lumen.

Mucosal trypsin, a protease-activated receptor (PAR) stimulant, may have an endogenous bronchoprotective role on airway smooth muscle. To test this possibility the effects of lumenal trypsin on airway tone in segments of pig bronchus were tested. Bronchial segments from pigs were mounted in an organ chamber containing Kreb's solution. Contractions were assessed from isovolumetric lumen pressure induced by acetylcholine (ACh) or carbachol added to the adventitia. Trypsin, added to the airway lumen (300 microg x mL(-1)), had no immediate effect on smooth muscle tone but suppressed ACh-induced contractions after 60 min, for at least 3 h. Synthetic activating peptides (AP) for PAR1, PAR2 or PAR3 were without effect, but PAR4 AP caused rapid, weak suppression of contractions. Lumenal thrombin was without effect and did not prevent the effects of trypsin. Effects of trypsin were reduced by N(omega)-nitro-L-arginine methyl ester but not indomethacin. Trypsin, thrombin and PAR4 AP released prostaglandin E2. Adventitially, trypsin, thrombin and PAR4 AP (but not PAR2 AP) relaxed carbachol-toned airways after <3 min. The findings of this study show that trypsin causes delayed and persistent bronchoprotection by interacting with airway cells accessible from the lumen. The signalling mechanism may involve nitric oxide synthase but not prostanoids or protease-activated receptors.     

脑卒中急性期白细胞反应及临床意义

脑卒中急性期大多数患者白细胞增多，表现为中性粒细胞计数与白细胞总数增高，脑出血组白细胞增高姓率高于脑梗塞组，而中性粒细胞增高发生率二组间无差别，外周血白细胞增高与临床神经功能缺损程度评分有密切关系，中性粒细胞计数越高，近期神经功能预后则越差。     

De-novo expression of vascular ecto-5′-nucleotidase and down-regulation of glomerular ecto-ATPase in experimental chronic renal transplant failure

Ischemic injury plays an important role in chronic renal transplant failure (CRTF). Down-regulation of ecto-adenosine triphosphatase (ATPase) in combination with up-regulation of ecto-5'-nucleotidase is a hallmark of ischemic injury. We studied the expression of renal ecto-5'-nucleotidase and ecto-ATPase in experimental renal transplantation. Fisher 344-to-Lewis allografted rats were either treated with an angiotensin-converting enzyme inhibitor (ACEi) or left untreated. Lewis-to-Lewis syngrafted rats served as controls. Untreated allografted rats developed proteinuria, glomerulosclerosis, and mild intimal hyperplasia. ACEi completely prevented focal and segmental glomerulosclerosis (FGS) and proteinuria, but significantly enhanced intimal hyperplasia. Untreated allografted rats revealed marked vascular ecto-5'-nucleotidase activity, which increased with ACEi. Vascular ecto-5'-nucleotidase activity was absent in syngrafted animals. Ecto-5'-nucleotidase activity correlated well with intimal hyperplasia. Glomerular ecto-ATPase expression was significantly reduced in untreated allografted rats compared to syngrafted rats and correlated well with the extent of FGS. ACEi prevented reduction in glomerular ecto-ATPase. We found de-novo expression of ecto-5'-nucleotidase at sites of renal intimal hyperplasia. Glomerular ecto-ATPase expression was markedly reduced in allografted rats and was prevented by ACEi. These enzyme expression patterns suggest local ischemic damage in experimental CRTF.     

The value of MCA, CA 15-3, CEA and CA-125 for discrimination between metastatic breast cancer and adenocarcinoma of other primary sites

MCA, CA 15-3, CEA and CA 125 were determined in the serum of 49 patients with metastatic breast cancer and 38 patients with metastatic adenocarcinoma of other primary sites. By using the 99th percentile of the normal value distribution as the cut-off point, the positive predictive value (PV+) was found to be 85% (95% CI 76-94) for MCA, and 71% (95% CI 61-81) for CA 15-3. When receiver-operating-characteristic (ROC) curves were constructed, the PV+ for CA 15-3 was increased to 82% (95% CI 72-92), using 60 U ml-1 as the cut-off point. With the exception of two patients who had a slightly elevated MCA, MCA and CA 15-3 identified the same patients with breast cancer. By combining a positive MCA or CA 15-3 with a negative CEA and CA 125, further improvement of the PV+ could be achieved; 100% (95% CI 91-100). We conclude that MCA and CA 15-3 may play a useful role in discrimination between patients with metastatic breast cancer and those with adenocarcinoma of other primary sites.     

P6 Complaints of halitosis related to the oral cavity. A preliminary report of 700 consecutive patients

Patients with complaints of halitosis do seek treatment from physicians and dental practitioners, because of the fear that their halitosis may interfere with their social activities. Although the prevalence of halitosis has been reported to be as high as 50%, most physicians and dental practitioners are poorly informed about the causes and treatments of halitosis. In order to care for patients with complaints of halitosis a multidisciplinary team was established at the Erasmus Medical Centre, Rotterdam, The Netherlands. The team included a dental hygienist, an otorhinolaryngologist, and a dentist, who developed a special halitosis programme. One short press release regarding the establishment of the team, was provided to the national press-centre. In the out-patient clinic more than 700 patients were seen by the team. Using a structured questionnaire fed to a PC, patients answered questions regarding complaints about the oral cavity, the upper respiratory tract, the throat, their general health, their cleansing habits of the oral cavity, and prior experiences with general physicians, dental practitioners, and medical specialists. They underwent examinations of the extent of their halitosis, of the perioral and neck region, the oral cavity, the upper respiratory tract, and the upper digestive tract. Finally, the members of the team came to a joint diagnosis and a joint treatment plan for every individual patient. Of the first 700 consecutive patients around 90% had a natural dentition without removable partial dentures. More than 60% were diagnosed as having periodontal disease with pockets of 4 mm or more in the maxilla. This figure was more than 50% in the mandible. Around 95% had tongue coating.