Estimation of renal function immediately after cessation of continuous renal replacement therapy at the ICU.

Estimating glomerular filtration (eGFR) after Continuous Renal Replacement Therapy (CRRT) is important to guide drug dosing and to assess the need to re-initiate CRRT. Standard eGFR equations cannot be applied as these patients neither have steady-state serum creatinine concentration nor average muscle mass. In this study we evaluate the combination of dynamic renal function with CT-scan based correction for aberrant muscle mass to estimate renal function immediately after CRRT cessation. We prospectively included 31 patients admitted to an academic intensive care unit (ICU) with a total of 37 CRRT cessations and measured serum creatinine before cessation (T1), directly (T2) and 5 h (T3) after cessation and the following two days when eGFR stabilized (T4, T5). We used the dynamic creatinine clearance calculation (D3C) equation to calculate eGFR (D3CGFR) and creatinine clearance (D3Ccreat) between T2-T3. D3Ccreat was corrected for aberrant muscle mass when a CT-scan was available using the CRAFT equation. We compared D3CGFR to stabilized CKD-EPI at T5 and D3CCreat to 4-h urinary creatinine clearance (4-h uCrCl) between T2-T3. We retrospectively validated these results in a larger retrospective cohort (NICE database; 1856 patients, 2064 cessations). The D3CGFR was comparable to observed stabilized CKD-EPI at T5 in the prospective cohort (MPE = - 1.6 ml/min/1.73 m2, p30 = 76%) and in the retrospective NICE-database (MPE = 3.2 ml/min/1.73 m2, p30 = 80%). In the prospective cohort, the D3CCreat had poor accuracy compared to 4-h uCrCl (MPE = 17 ml/min/1.73 m2, p30 = 24%). In a subset of patients (n = 13) where CT-scans were available, combination of CRAFT and D3CCreat improved bias and accuracy (MPE = 8 ml/min/1.73 m2, RMSE = 18 ml/min/1.73 m2) versus D3CCreat alone (MPE = 18 ml/min/1.73 m2, RMSE = 32 ml/min/1.73 m2). The D3CGFR improves assessment of eGFR in ICU patients immediately after CRRT cessation. Although the D3CCreat had poor association with underlying creatinine clearance, inclusion of CT derived biometric parameters in the dynamic renal function algorithm further improved the performance, stressing the role of muscle mass integration into renal function equations in critically ill patients.

Evaluation of new alternative methods for the identification of estrogenic, androgenic and steroidogenic effects: a comparative in vitro/in silico study.

A suite of in vitro assays and in silico models were evaluated to identify which best detected the endocrine-disrupting (ED) potential of 10 test chemicals according to their estrogenic, androgenic and steroidogenic (EAS) potential compared to the outcomes from ToxCast. In vitro methods included receptor-binding, CALUX transactivation, H295R steroidogenesis, aromatase activity inhibition and the Yeast oestrogen (YES) and Yeast androgen screen (YAS) assays. The impact of metabolism was also evaluated. The YES/YAS assays exhibited a high sensitivity for ER effects and, despite some challenges in predicting AR effects, is a good initial screening assay. Results from receptor-binding and CALUX assays generally correlated and were in accordance with classifications based on ToxCast assays. ER agonism and AR antagonism of benzyl butyl phthalate were abolished when CALUX assays included liver S9. In silico final calls were mostly in agreement with the in vitro assays, and predicted ER and AR effects well. The efficiency of the in silico models (reflecting applicability domains or inconclusive results) was 43-100%. The percentage of correct calls for ER (50-100%), AR (57-100%) and aromatase (33-100%) effects when compared to the final ToxCast call covered a wide range from highly reliable to less reliable models. In conclusion, Danish (Q)SAR, Opera, ADMET Lab LBD and ProToxII models demonstrated the best overall performance for ER and AR effects. These can be combined with the YES/YAS assays in an initial screen of chemicals in the early tiers of an NGRA to inform on the MoA and the design of mechanistic in vitro assays used later in the assessment. Inhibition of aromatase was best predicted by the Vega, AdmetLab and ProToxII models. Other mechanisms and exposure should be considered when making a conclusion with respect to ED effects.

Multimodal prehabilitation to reduce the incidence of delirium and other adverse events in elderly patients undergoing elective major abdominal surgery: An uncontrolled before-and-after study.

BACKGROUND: Delirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients. METHODS: A single-center uncontrolled before-and-after study was conducted, including patients aged 70 years or older who underwent elective abdominal surgery for colorectal carcinoma or an abdominal aortic aneurysm between January 2013 and October 2015 (control group) and between November 2015 and June 2018 (prehabilitation group). The prehabilitation group received interventions to improve patients' physical health, nutritional status, factors of frailty and preoperative anaemia prior to surgery. The primary outcome was incidence of delirium, diagnosed with the DSM-V criteria or the confusion assessment method. Secondary outcomes were additional complications, length of stay, unplanned ICU admission, length of ICU stay, readmission rate, institutionalization, and in-hospital or 30-day mortality. RESULT: A total of 360 control patients and 267 prehabilitation patients were included in the final analysis. The mean number of prehabilitation days was 39 days. The prehabilitation group had a higher burden of comorbidities and was more physically and visually impaired at baseline. At adjusted logistic regression analysis, delirium incidence was reduced significantly from 11.7 to 8.2% (OR 0.56; 95% CI 0.32-0.98; P = 0.043). No statistically significant effects were seen on secondary outcomes. CONCLUSION: Current prehabilitation program is feasible and safe, and can reduce delirium incidence in elderly patients undergoing elective major abdominal surgery. This program merits further evaluation. TRIAL REGISTRATION: Dutch Trial Registration, NTR5932.

High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury.

PURPOSE: Lung transplant recipients often develop acute kidney injury (AKI) evolving into chronic kidney disease (CKD). The immunosuppressant tacrolimus might be associated with the emergence of AKI. We analyzed the development and recovery of kidney injury after lung transplantation and related AKI to whole-blood tacrolimus trough concentrations and other factors causing kidney injury. METHODS: We retrospectively studied kidney injury in 186 lung-transplantation patients at the UMC Utrecht between 2001 and 2011. Kidney function and whole-blood tacrolimus trough concentrations were determined from day 1 to 14 and at 1, 3, 6, and 12 months postoperative. Systemic inflammatory response syndrome (SIRS), septic shock, and nephrotoxic medications were evaluated as covariates for AKI. We analyzed liver injury and drug-drug interactions. RESULTS: AKI was present in 85 (46%) patients. Tacrolimus concentrations were supra-therapeutic in 135 of 186 patients (73%). AKI in the first week after transplantation was related to supra-therapeutic tacrolimus concentrations (OR 1.55; 95% CI 1.06-2.27), ≥3 other nephrotoxic drugs (OR 1.96; 95% CI 1.02-3.77), infection (OR 2.48; 95% CI 1.31-4.70), and cystic fibrosis (OR 2.17; 95% CI 1.16-4.06). Recovery rate of AKI was lower than expected (19%), and the cumulative incidence of severe CKD at 1 year was 15%. CONCLUSIONS: After lung transplantation, AKI is common and often evolves into severe CKD, which is a known cause of morbidity and mortality. Supra-therapeutic whole-blood tacrolimus trough concentrations are related to the early onset of AKI. Conscientious targeting tacrolimus blood concentrations might be vital in the early phase after lung transplantation. What is known about this subject? • Lung transplant recipients often develop acute kidney injury evolving into chronic kidney disease increasing both morbidity and mortality. • To date, the pathophysiology of kidney injury after lung transplantation has not been fully elucidated. • The immunosuppressant tacrolimus is difficult to dose, especially in the unstable clinical setting, and is nephrotoxic. WHAT THIS STUDY ADDS: • For the first time, supra-therapeutic whole-blood tacrolimus trough concentrations are related to the emergence of acute kidney injury in the first days after lung transplantation. • Supra-therapeutic whole-blood tacrolimus trough concentrations often occur early after lung transplantation. • AKI after lung transplantation shows low recovery rates.

Risk factors of post-operative delirium after elective vascular surgery in the elderly: A systematic review.

BACKGROUND: Postoperative delirium is a common and serious adverse event in the elderly patient and is associated with significant morbidity and mortality. It is of great importance to identify patients at risk for delirium, in order to focus preventive strategies. The aim of this article is to systematically review current available literature on pre-operative risk factors for delirium after vascular surgery. METHODS: A systematic literature search was conducted using PubMed and EMBASE, using the MeSH terms and key words "delirium", "surgery" and "risk factor". Studies were retained for review after meeting strict inclusion criteria that included only prospective studies evaluating risk factors for delirium in patients who had elective vascular surgery. Diagnosis of delirium needed to be confirmed using the Diagnostic and Statistical Manual of Mental Disorders (DSM) or ICD-10. RESULTS: Fifteen articles were selected for inclusion, incidence of delirium across the studies ranged from 5% to 39%. Many factors have been associated with increased risk of delirium, including age, cognitive impairment, comorbidity, depression, smoking, alcohol, visual and hearing impairment, ASA-score, biochemical abnormalities, operative strategies and blood loss. CONCLUSIONS: Delirium is a common complication after elective vascular surgery in elderly. The highest delirium incidence was observed after open aortic surgery as well as after surgery for critical limb ischemia. A picture starts to form of which predisposing factors lead to increased risk of delirium. The leading risk factors consistently identified in this systematic review were advanced age and cognitive impairment. Multi-disciplinary specialist-led interventions in the preoperative phase could decrease incidence and severity of delirium and should be focused on identified high-risk patients.

BRCA1 Reflects Myocardial Adverse Remodeling in Idiopathic Dilated Cardiomyopathy.

BACKGROUND: The role of BRCA1 in chronic ischemic episodes seems to be pivotal for adverse remodeling and development of ischemic cardiomyopathy, because of its role in DNA repair and apoptosis. The aim of this study was to investigate the role of BRCA-1 in idiopathic dilated cardiomyopathy (IDCM). MATERIAL AND METHODS: The study group (IDCM) comprised myocardial samples from hearts explanted before transplantation owing to IDCM in 10 males (age 44 ± 5.3 years) without clinical symptoms of ischemic heart disease. The control group consisted myocardial fragments taken from 10 male heart valve and pulmonary artery donors with diagnosed cerebral death (age 40 ± 2.3 years). BRCA1 was detected immunohistochemically with rabbit anti-BRCA1 polyclonal antibody. The intensity of BRCA1 expression was semiquantitatively assessed for cardiocytes, small vessels including capillaries, and interstitial cells. The significances between groups were estimated using the Mann-Whitney U test. RESULTS: All IDCM cases were positive and presented nonuniform BRCA1 expression: hypertrophied cardiocytes showed very intense staining and typical cardiomyopathic cardiocytes were stained weakly forming mosaic. Control cases showed weak-to-moderate uniform staining. Intensity of staining was significantly higher in IDCM cardiocytes, whereas small vessels and interstitial were stained similarly in both groups. CONCLUSIONS: IDCM adverse remodeling results in more intense but nonuniform BRCA1 expression. This phenomenon seems to reflect IDCM biology: lower BRCA1 expression in myocytes with lower anti-apoptotic and DNA damage repair activity, with the opposite in hypertrophied myofibers.

Correspondence of cytological and histopathological diagnoses in diagnostic category V of the Bethesda system: "suspicious for malignancy".

The progress in imaging methods enables fine needle aspiration (FNA) biopsy to be performed on smaller and smaller lesions, including malignant ones (papillary microcarcinomas). The follicular variant predominates in this group, with cytological features often not permitting an unbiased interpretation. The aim of the study was to determine the degree of reliability of the "suspicious for malignancy" (SM) diagnosis in material from the Institute of Oncology in Gliwice (IO). 290 primary SM diagnoses were established from 2010 to 2015 in the IO, including the consultations. None of the patients was treated surgically after the first FNA resulting in diagnostic category V (DC V). After the second FNA 80 patients underwent surgery, after the third 58, and after subsequent FNA 10. Together, 148 surgical resections were performed. Among 148 patients treated surgically, 111 were diagnosed with malignant lesions, which constitutes 75%. Predominantly - in 91 cases - the histopathological outcome was papillary carcinoma. The others were: 16 medullary carcinomas, 2 follicular carcinomas, and 2 poorly differentiated carcinoma cases. Moreover, 8 follicular adenomas and 28 nonneoplastic lesions were found. The high positive predictive value (PPV = 75%) of SM diagnosis established in the IO testifies to the high reliability of this test. Diagnostic category V in FNA should be an indication for surgical treatment.

The diagnosis of cancer in thyroid fine needle aspiration biopsy. Surgery, repeat biopsy or specimen consultation?

Fine needle aspiration biopsy (FNA) is the only diagnostic method that allows a preoperative diagnosis of thyroid carcinoma. An unequivocal diagnosis of a malignant change is achievable only in cases in which all cytological criteria of carcinoma are met. The aim of the study was to evaluate the necessity of repeat thyroid FNA in patients with papillary thyroid carcinoma verified on consultative examination (CE). We analyzed cytology reports of thyroid FNA and CE that resulted in the diagnosis of papillary carcinoma. Evaluation of the correlation of the cytological diagnosis with the histopathology report was based on data obtained after the surgery. Between 2010 and 2015 in the Institute of Oncology (IO) there were 184 cancers diagnosed on CE or in thyroid FNA performed primarily in IO. Additionally, 74 patients were subjected to repeat biopsy after confirmation of cancer in CE. Histopathological diagnosis of cancer was obtained in 62 (100%) cases that were doubly confirmed with cytological examination. The remaining 12 patients were operated on outside the institute. From 110 FNA primarily performed in the IO, histopathological verification was achievable in 92 cases, from which 92 (100%) provided a confirmation of cancer, and the remaining 18 patients were operated on outside the institute. High (100%) specificity of cancer diagnosis in FNA established primarily and verified on CE (second independent assessment) indicates that repeat FNA in order to confirm the diagnosis is unnecessary.

Motor cortex glutathione deficit in ALS measured in vivo with the J-editing technique.

This study compared in vivo levels of the antioxidant glutathione (GSH) in the motor cortex of 11 ALS patients with those in 11 age-matched healthy volunteers (HV). Using the standard J-edited spin-echo difference MRS technique, GSH spectra were recorded on a 3.0 T GE MR system from a single precentral gyrus voxel. GSH levels expressed as ratios to the unsuppressed voxel tissue water (W) were 31% lower in ALS patients than in HV (p=.005), and 36% lower in ALS than in HV (p=.02) when expressed as ratios to the total creatine peak (tCr), supporting a role for oxidative stress in ALS. Levels of the putative neuronal marker N-acetylaspartate (NAA) relative to W did not differ between ALS and HV (p=.26), but were lower by 9% in ALS than in HV (p=.013) when expressed as ratios relative to tCr. This discrepancy is attributed to small but opposite changes in NAA and tCr in ALS that, as a ratio, resulted in a statistically significant group difference, further suggesting caution in using tCr as an internal reference under pathological conditions.

Ethylene glycol or methanol intoxication: which antidote should be used, fomepizole or ethanol?

Ethylene glycol (EG) and methanol poisoning can cause life-threatening complications. Toxicity of EG and methanol is related to the production of toxic metabolites by the enzyme alcohol dehydrogenase (ADH), which can lead to metabolic acidosis, renal failure (in EG poisoning), blindness (in methanol poisoning) and death. Therapy consists of general supportive care (e.g. intravenous fluids, correction of electrolytes and acidaemia), the use of antidotes and haemodialysis. Haemodialysis is considered a key element in the treatment of severe EG and methanol intoxication and is aimed at removing both the parent compound and its toxic metabolites, reducing the duration of antidotal treatment and shortening the hospital observation period. Currently, there are two antidotes used to block ADH-mediated metabolism of EG and methanol: ethanol and fomepizole. In this review, the advantages and disadvantages of both antidotes in terms of efficacy, safety and costs are discussed in order to help the physician to decide which antidote is appropriate in a specific clinical setting.

Extracorporeal membrane oxygenation in the treatment of poisoned patients.

CONTEXT: Although extracorporeal membrane oxygenation (ECMO) was used in many patients following its introduction in 1972, most hospitals had abandoned this experimental treatment for adult patients. Recently, improvements in the ECMO circuitry rendered it more biocompatible. The surprisingly low mortality in patients with severe acute respiratory distress syndrome who were treated with ECMO in the influenza A/H1N1 pandemic of 2009 resurrected interest in ECMO in many intensive care units around the world. OBJECTIVES: This article reviews the different techniques of ECMO, the indications, contraindications and complications of its use, its role in poisoned patients and the ethics of its use. METHODS: We searched Pubmed, Toxnet, Cochrane database and Embase from 1966 to September 2012 using the search terms (''extracorporeal membrane oxygenation'', 'extracorporeal life support', 'ECMO', 'ECLS', 'assist-device', and 'intox*' or 'poison*'). These searches identified 242 papers of which 116 described ECMO in conditions other than intoxications or were reviews. In total 46 publications selected for this manuscript were case reports or case series involving poisoned patients. ECMO TECHNIQUES: Two types of ECMO are used: veno-venous ECMO (VV-ECMO) or veno-arterial ECMO (VA-ECMO). VV-ECMO is used for patients with severe ARDS to secure adequate oxygenation of the organs while protecting the lungs from harmful ventilation pressures or prolonged inspiratory fraction of oxygen. VA-ECMO can be used whenever the patient remains in shock despite adequate fluid resuscitation and is refractory to administration of inotropes and vasopressors. INDICATIONS: The organ support that can be applied with ECMO makes it especially useful in patients with severe poisoning as the clinical impact of the intoxication is often temporary; ECMO can be used as a 'bridge to recovery'. CONTRAINDICATIONS: Absolute contraindications are uncontrolled coagulopathy and severe intracranial bleeding, which precludes the use of anticoagulation therapy. Relative contraindications to ECMO include advanced age, severe irreversible brain injury, untreatable metastatic cancer, severe organ dysfunction (some suggest a Sequential Organ Failure Assessment (SOFA) score > 15), and high pressure positive pressure ventilation for more than 7 days. COMPLICATIONS: The most common complication of ECMO is either bleeding at the cannulation site (in VV-ECMO) or bleeding at the surgical entry site (in VA-ECMO). Overall bleeding complications currently occur in 10-36% patients, and intracranial haemorrhage is seen in up to 6% of patients. ECMO should be reserved, therefore, for the most severely ill poisoned patients with a high risk of death. ECMO in poisoned patients. There are no randomised trials of ECMO in poisoned patients with refractory shock or who have ARDS caused by an intoxication. VV-ECMO can be considered in patients with type l and ll respiratory failure. In patients with life-threatening haemodynamic instability, VA-ECMO can be considered when shock persists despite volume administration, inotropes and vasoconstrictors, and (sometimes) intra-aortic balloon counterpulsation. Typical examples include poisoning due to calcium channel antagonists, beta-blockers, tricyclic antidepressants, chloroquine and colchicine. ETHICS OF ECMO USE: It is only ethical to use such a costly intervention (£19,252 and US$ 31,000 per quality-adjusted life year) if the treatment has a real purpose such as a 'bridge to recovery', a 'bridge to transplant', or a 'bridge to permanent assist device' (in the case of persistent cardiac failure). CONCLUSIONS: In the last decade, ECMO equipment has improved considerably, rendering it more biocompatible, and it has been used more frequently as an assist device for patients needing oxygenation as well as circulatory support. ECMO is considered a good salvage therapy for patients who are severely poisoned with ARDS or refractory circulatory shock.

Paradox of advanced glycation end-products in late cardiac biopsies of heart transplant recipients.

BACKGROUND: A pilot study of orthotopic heart transplant (OHT) recipients showed that advanced glycation end-product (AGE) deposits were related to acute rejection episodes among subjects with diabetes mellitus (DM); in contrast, among non-DM patients it was associated with prolonged freedom from coronary artery vasculopathy (CAV). However the number of observations in non-diabetic subjects was low. The aim of the current study was to establish the role of AGEs in late endomyocardial biopsies (EMBs) among a larger group of non-diabetic patients. MATERIAL AND METHODS: Elective EMBs were performed at 3 years post OHT in 62 subjects with DM, namely, 57 males and 5 females of overall mean age of 50±8 years versus 92 free of DM, including 79 males and 13 females of mean age 51±13 years. We localized AGEs in myocardial paraffin sections using monoclonal mouse anti-AGE antibodies. The presence of AGEs in cardiomyocytes, stromal cells, capillaries, and arterioles was described with a semiquantitative scale. RESULTS: All-cause deaths, CAV, and CAV-related events were observed in 28% versus 23%, 27% versus 29%, and 15% versus 19% of non-DM versus DM patients (P=NS). The occurrence of AGEs was significantly more frequent among non-DM than DM subjects: cardiocytes, 100% versus 69% (P<.0001); stroma, 54% versus 31% (P=.0037); capillaries, 67% versus 31% (P<.0001); and arterioles, 26% versus 3% (P=.0002; chi-square). Among the DM group, mean EMB score correlated with AGE presence in cardiomyocytes (n=0.29; P<.05, Spearman test) AGE presence had no impact on survival or CAV development. CONCLUSION: AGE presence was more common in late EMB from non-diabetic than diabetic OHT recipients; they had no impact on survival or CAV in non-diabetic patients.

Candidemic complications in patients with intravascular catheters colonized with Candida species: an indication for preemptive antifungal therapy?

BACKGROUND: The impact of Candida-colonized catheter tips in patients without candidemia is unclear. METHODS: A retrospective study of patients with tip cultures positive for Candida was conducted over an 8-year period, to determine the outcomes in patients with Candida cultured from an intravascular catheter tip in the absence of preceding Candida-positive blood cultures. The primary outcome measure was definite candidemia. Secondary outcomes included possible candidemia and in-hospital mortality. A possible candidemia was defined as clinical signs and symptoms of invasive candidiasis without explanation other than a candidemia, but with negative blood cultures. RESULTS: Sixty-eight cultures from 64 patients were included in the study. Definite candidemia developed in three cases (4%) and possible candidemia developed in five cases (7%). In-hospital mortality was significantly increased in patients with definite or possible candidemia (63% vs. 22%, p=0.028). Risk factors for the development of definite or possible candidemia were catheter time in situ >8 days (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.1-32.9) and abdominal surgery (OR 6.0, 95% CI 1.1-32.4). CONCLUSIONS: Intravascular catheter tip colonization in patients without preceding blood cultures with Candida is associated with candidemia in from 4% of patients (definite candidemia) up to 12% of patients (definite and possible candidemia combined). Considering the adverse prognosis associated with delayed treatment of candidemia, preemptive treatment based on catheter tip cultures might outweigh the disadvantages of costs and side effects of antifungal therapy.

Associations between neighbourhood characteristics, body mass index and health-related behaviours of adolescents in the Kiel Obesity Prevention Study: a multilevel analysis.

BACKGROUND/OBJECTIVES: To understand determinants of overweight, several studies addressed the association between neighbourhood characteristics and adult obesity. However, little is known about the association of such characteristics with adolescents' overweight. This study aims at the influence of neighbourhood characteristics on adolescent body mass index (BMI) and lifestyle and to what extent BMI and lifestyle variation between neighbourhoods can be explained by neighbourhood characteristics. SUBJECTS/METHODS: We used cross-sectional data from the Kiel Obesity Prevention Study collected between 2004 and 2008 in 28 different residential districts of the city of Kiel (North Germany). Anthropometric data were available for 1675 boys and 1765 girls (n=3440) aged 13-15 years, and individual lifestyle factors and sociodemographic data were included in the analysis. At the macro level, six different neighbourhood characteristics were used: unemployment rate, population density, traffic density, prevalence of energy-dense food supply, number of sports fields and parks, and crime rate. To test our main hypothesis, linear and logistic multilevel regression analyses were performed to predict BMI and lifestyle factors in individuals nested in neighbourhoods. RESULTS: Findings of multilevel analysis show little between-neighbourhood variations in BMI and health-related behaviours. In all, 2% of BMI variation, 4% of media time variation and 3% of variation in snacking behaviour could be attributed to differences in neighbourhoods. CONCLUSIONS: Environmental factors are significantly associated with adolescent BMI and health-related behaviour; however, their total effect is small. Owing to these results, recommendations for structural policy measures as part of prevention of overweight in adolescents must be made cautiously.

Greenstick fractures of the middle third of the forearm. A prospective multi-centre study.

BACKGROUND: Greenstick fractures suffered during growth have a high risk for refracture and posttraumatic deformity, particularly at the forearm diaphysis. The use of a preemptive completion of the fracture by manipulation of the concave cortex is controversial and data supporting this approach are few. AIM: Aim of this study was to determine the factors which predispose to refracture and deformities, and to define therapeutic strategies. METHODS: We prospectively gathered clinical and radiographic data over a period of one year on greenstick fractures of the middle third of the forearm in children as part of a multi-centre study. Endpoint was a follow-up visit at one year. Radiographic deformity, state of consolidation at resumption of physical activities and refracture rate were analysed statistically (ANOVA, Student's t-test and Pearson's chi-square test) with regard to patient age, gender, fracture type, therapy and time in plaster. RESULTS: We collected the data of 103 patients (63 boys, 40 girls), average age 6.6 years (1.3-14.5 years), the vast majority of whom had a combined greenstick fracture of the radius and ulna. 6.7% of the patients sustained a refracture within 49 days (29-76) after plaster removal. They were significantly older (p=0.017) with a significantly higher incidence of manual completion of the fracture with radiographic signs of partial consolidation (p=0.025). Residual deformities were significantly smaller after completion of the fracture compared to reduction without completion (p=0.019) or plaster fixation alone (p<0.005). CONCLUSIONS: Completion of a greenstick fracture does not prevent refracture. Nevertheless, it diminishes the extent of secondary deformities in cases where the primary angulation exceeds the remodelling capacity. Prevention of refracture should include a routine radiographic follow-up 4-6 weeks after injury with continuation of plaster fixation in cases of partial consolidation.

Inguinal hernia surgery in The Netherlands: are patients treated according to the guidelines?

PURPOSE: In 2003, a dedicated Dutch committee developed evidence-based guidelines for the treatment of inguinal hernia (IH) in children and adults. The aim of this study was to describe trends in hernia care before and after the publication of the guidelines on IH surgery in The Netherlands. METHODS: Originally, a retrospective baseline analysis of IH surgery in 90 Dutch hospitals was performed among patients treated for IH in 2001. The results of this baseline analysis were compared with a recently performed second analysis of patients treated for IH in 2005. RESULTS: In children <4 years of age, the study showed a significant decrease of contralateral explorations. In adults, the study showed that significantly more patients were treated with a mesh-based repair in 2005 (95.9 vs. 78.8%, P < 0.01). Moreover, there was an increase of patients with bilateral hernia treated with an endoscopic technique (41.5 vs. 22.3%, P < 0.01) and more patients were treated in day surgery (53.5 vs. 38.6%, P < 0.01). Lastly, a decline in operations performed for recurrent IH in adults was observed (10.9 vs. 13.3%, P < 0.01). CONCLUSION: This study showed that most patients with IH in The Netherlands were treated according to the main recommendations of the Dutch evidence-based guidelines.

Differences in antiapoptotic, proliferative activities and morphometry in dilated and ischemic cardiomyopathy: study of hearts explanted from transplant recipients.

BACKGROUND: Antiapoptotic as well as replacement and proliferative mechanisms take place in the myocardium in dilated cardiomyopathy (DCM) and ischemic heart disease (IHD). We sought to estimate antiapoptotic, proliferative and replacement activities in cardiomyopathies. MATERIALS: The study groups included seven hearts with DCM and eight with IHD, which had been explanted at the time of transplantation. The comparator group consisted of cases of myocardial hypertrophy and the control group, donor fragments. METHODS: Antiapoptotic and proliferative responses were determined immunohistochemically as Bcl-2 and Ki67 expression by semiquantitative assessment of the intensity of staining. We also measured and statistically analyzed the integrative morphometric measurements of the fraction of fibrosis area, the nucleosarcoplasmic ratio, and cardiocyte diameter. RESULTS: No Bcl-2 expression was observed in the controls. The strongest reaction was seen in the DCM group, then in the IHD, and in the comparator group of myocardial hypertrophy. Proliferative activity was seen only in endocardial and interstitial fibroblasts in DCM and IHD cases. The cardiocyte diameter showed no statistical association between myocardial hypertrophy and IHD, or IHD and DCM, whereas the nucleosarcoplasmic ratios were significantly different from control groups for all comparisons. Myocardial fibrosis showed the highest values in DCM and IHD. Discriminant analysis showed the value of interstitial fibrosis and cardiocyte diameter to categorize the analyzed groups. CONCLUSIONS: Antiapoptotic Bcl-2 activity seemed to play an important role in cardiocyte preservation, while proliferative activity was resticted to interstitial connective tissue cells as a replacement process. Myocardial Bcl-2 expression, the extent of myocardial fibrosis, and cardiocyte diameter may serve as additional diagnostic tools to differentiate cardiomyopathies.

European Hernia Society guidelines on the treatment of inguinal hernia in adult patients.

The European Hernia Society (EHS) is proud to present the EHS Guidelines for the Treatment of Inguinal Hernia in Adult Patients. The Guidelines contain recommendations for the treatment of inguinal hernia from diagnosis till aftercare. They have been developed by a Working Group consisting of expert surgeons with representatives of 14 country members of the EHS. They are evidence-based and, when necessary, a consensus was reached among all members. The Guidelines have been reviewed by a Steering Committee. Before finalisation, feedback from different national hernia societies was obtained. The Appraisal of Guidelines for REsearch and Evaluation (AGREE) instrument was used by the Cochrane Association to validate the Guidelines. The Guidelines can be used to adjust local protocols, for training purposes and quality control. They will be revised in 2012 in order to keep them updated. In between revisions, it is the intention of the Working Group to provide every year, during the EHS annual congress, a short update of new high-level evidence (randomised controlled trials [RCTs] and meta-analyses). Developing guidelines leads to questions that remain to be answered by specific research. Therefore, we provide recommendations for further research that can be performed to raise the level of evidence concerning certain aspects of inguinal hernia treatment. In addition, a short summary, specifically for the general practitioner, is given. In order to increase the practical use of the Guidelines by consultants and residents, more details on the most important surgical techniques, local infiltration anaesthesia and a patient information sheet is provided. The most important challenge now will be the implementation of the Guidelines in daily surgical practice. This remains an important task for the EHS. The establishment of an EHS school for teaching inguinal hernia repair surgical techniques, including tips and tricks from experts to overcome the learning curve (especially in endoscopic repair), will be the next step. Working together on this project was a great learning experience, and it was worthwhile and fun. Cultural differences between members were easily overcome by educating each other, respecting different views and always coming back to the principles of evidence-based medicine. The members of the Working Group would like to thank the EHS board for their support and especially Ethicon for sponsoring the many meetings that were needed to finalise such an ambitious project.

HSP27 diagnostic utility in the fine needle aspirate of breast. Correlation with progesterone and estrogen receptors.

Fine needle aspiration (FNA) is routine diagnostic tool in breast tumors assessment. In some cases, however, limitations of this method do not permit an unequivocal diagnosis. In these, suspected, cases immunocytochemical evaluation of selected biological markers may be of help. The aim of the study was assessment of HSP27 value in diagnosis and discrimination of benign and malignant breast lesions. HSP27 expression was examined by immunocytochemistry in fine needle aspiration smears assessed to C2-C5 categories. In C5 subgroup HSP27 expression was correlated with ER, PR content. Statistically significant differences in HSP27 expression between subsets C2/C5 and C3/C5 were found (p=0.028 and p=0,04, respectively); the differences between C3/C4 categories were not significant. Expression of HSP27 protein in FNA smears can be additional factor, which helps to differentiate benign, and malignant breast lesions, however it is not useful for discrimination of cytological, suspicious lesions.