Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy: a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and 1H-MR spectroscopy compared with histology (subgroup in the RAXO trial).

BACKGROUND: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. PATIENTS AND METHODS: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusion-weighted imaging and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and Kaplan-Meier estimates of overall survival (OS). RESULTS: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). 1H-MRS revealed steatohepatosis induced by systemic therapy. CONCLUSIONS: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.

Optimising the antibiotic treatment of uncomplicated acute appendicitis: a protocol for a multicentre randomised clinical trial (APPAC II trial).

BACKGROUND: Based on epidemiological and clinical data acute appendicitis can present either as uncomplicated (70-80%) or complicated (20-30%) disease. Recent studies have shown that antibiotic therapy is both safe and cost-effective for a CT-scan confirmed uncomplicated acute appendicitis. However, based on the study protocols to ensure patient safety, these randomised studies used mainly broad-spectrum intravenous antibiotics requiring additional hospital resources and prolonged hospital stay. As we now know that antibiotic therapy for uncomplicated acute appendicitis is feasible and safe, further studies evaluating optimisation of the antibiotic treatment regarding both antibiotic spectrum and shorter hospital stay are needed to evaluate antibiotics as the first-line treatment for uncomplicated acute appendicitis. METHODS: APPAC II trial is a multicentre, open-label, non-inferiority randomised controlled trial comparing per oral (p.o.) antibiotic monotherapy with intravenous (i.v.) antibiotic therapy followed by p.o. antibiotics in the treatment of CT-scan confirmed uncomplicated acute appendicitis. Adult patients with CT-scan diagnosed uncomplicated acute appendicitis will be enrolled in nine Finnish hospitals. The intended sample size is 552 patients. Primary endpoint is the success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without the need for surgical intervention and no recurrent appendicitis during one-year follow-up. Secondary endpoints include post-intervention complications, late recurrence of acute appendicitis after one year, duration of hospital stay, pain, quality of life, sick leave and treatment costs. Primary endpoint will be evaluated in two stages: point estimates with 95% confidence interval (CI) will be calculated for both groups and proportion difference between groups with 95% CI will be calculated and evaluated based on 6 percentage point non-inferiority margin. DISCUSSION: To our knowledge, APPAC II trial is the first randomised controlled trial comparing per oral antibiotic monotherapy with intravenous antibiotic therapy continued by per oral antibiotics in the treatment of uncomplicated acute appendicitis. The APPAC II trial aims to add clinical evidence on the debated role of antibiotics as the first-line treatment for a CT-confirmed uncomplicated acute appendicitis as well as to optimise the non-operative treatment for uncomplicated acute appendicitis. TRIAL REGISTRATION: Clinicaltrials.gov , NCT03236961, retrospectively registered on the 2nd of August 2017.

Clinical Value of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Response Evaluation after Primary Treatment of Advanced Epithelial Ovarian Cancer.

AIMS: To prospectively evaluate the use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the definition of the treatment response after primary treatment of advanced epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Forty-nine patients with advanced EOC had an 18F-FDG PET/CT scan before and after primary treatment. The treatment response was defined with the currently used radiological and serological Response Criteria in Solid Tumors (RECIST1.1/GCIC) criteria and the modified PET Response Criteria in Solid Tumors (PERCIST). The concordance of the two methods was analysed. If the patient had a complete response to primary treatment by conventional criteria, the end of treatment 18F-FDG PET/CT scan (etPET/CT) was not opened until retrospectively at the time of disease progression. The ability of etPET/CT to predict the time to disease recurrence was analysed. The recurrence patterns were observed with an 18F-FDG PET/CT at the first relapse. RESULTS: The agreement of the RECIST1.1/GCIC and modified PERCIST criteria in defining the primary treatment response in the whole patient cohort was good (weighted kappa coefficient = 0.78). Of the complete responders (n = 28), 34% had metabolically active lesions present in the etPET/CT, most typically in the lymph nodes. The same anatomical sites tended to activate at disease relapse, but were seldom the only site of relapse. In patients with widespread intra-abdominal carsinosis at diagnosis, the definition of metabolic response was challenging due to problems in distinguishing the physiological FDG accumulation in the bowel loops from the residual tumour in the same area. The presence of metabolically active lesions in the etPET/CT did not predict earlier disease relapse in the complete responders. CONCLUSIONS: In the present study, etPET/CT revealed metabolically active lesions in complete responders after EOC primary therapy, but they were insignificant for the patient's prognosis. The current study does not favour routine use of 18F-FDG PET/CT after EOC primary treatment for complete responders.

The Accuracy of the Computed Tomography Diagnosis of Acute Appendicitis: Does the Experience of the Radiologist Matter?

BACKGROUND AND AIMS: To assess the accuracy of computed tomography in diagnosing acute appendicitis with a special reference to radiologist experience. MATERIAL AND METHODS: Data were collected prospectively in our randomized controlled trial comparing surgery and antibiotic treatment for uncomplicated acute appendicitis (APPAC trial, NCT01022567). We evaluated 1065 patients who underwent computed tomography for suspected appendicitis. The on-call radiologist preoperatively analyzed these computed tomography images. In this study, the radiologists were divided into experienced (consultants) and inexperienced (residents) ones, and the comparison of interpretations was made between these two radiologist groups. RESULTS: Out of the 1065 patients, 714 had acute appendicitis and 351 had other or no diagnosis on computed tomography. There were 700 true-positive, 327 true-negative, 14 false-positive, and 24 false-negative cases. The sensitivity and the specificity of computed tomography were 96.7% (95% confidence interval, 95.1-97.8) and 95.9% (95% confidence interval, 93.2-97.5), respectively. The rate of false computed tomography diagnosis was 4.2% for experienced consultant radiologists and 2.2% for inexperienced resident radiologists (p = 0.071). Thus, the experience of the radiologist had no effect on the accuracy of computed tomography diagnosis. CONCLUSION: The accuracy of computed tomography in diagnosing acute appendicitis was high. The experience of the radiologist did not improve the diagnostic accuracy. The results emphasize the role of computed tomography as an accurate modality in daily routine diagnostics for acute appendicitis in all clinical emergency settings.

Obstructive sleep apnea: the effect of bariatric surgery after 12 months. A prospective multicenter trial.

BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder, particularly in bariatric patients. It is known to be tightly linked with metabolic abnormalities and cardiovascular morbidity. Obesity is the most noteworthy individual risk factor for OSA. The aim of this study was to investigate the effect of a laparoscopic Roux-en-Y gastric bypass (LRYGB) on OSA one year after surgery. METHODS: In this prospective multicenter study standard overnight cardiorespiratory recording was conducted 12 months after bariatric surgery in 132 patients who had OSA in the baseline recording prior to the operation. The main outcome measures were changes in the prevalence of OSA and apnea-hypopnea index (AHI). In addition, the changes in anthropometric and demographic measurements including weight, body mass index (BMI), and waist and neck circumference were evaluated. A sleep symptom questionnaire was administered at baseline and at 12 months. RESULTS: The prevalence of OSA decreased from 71% at baseline to 44% at 12 months after surgery (p < 0.001). OSA was cured in 45% and cured or improved in 78% of the patients, but moderate or severe OSA still persisted in 20% of the patients after the operation. De novo OSA occurred in eight percent of the patients, and total AHI decreased from 27.8 events/h to 9.9 events/h (p < 0.001). CONCLUSIONS: LRYGB is effective in treating OSA. However, the findings demonstrate that a postoperative cardiorespiratory recording is needed in order to identify the patients with persistent moderate to severe OSA after the operation. CLINICAL TRIAL REGISTRATION: ClinalTrials.gov; No.: NCT01080404; URL: www.clinicaltrials.gov.

Associations of serum n-3 and n-6 polyunsaturated fatty acids with plasma natriuretic peptides.

BACKGROUND/OBJECTIVES: The n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been associated with lower risk of cardiovascular disease (CVD), but little is known about their association with natriuretic peptides (NPs), a marker for CVD risk. The aim of this study was to investigate the association of serum n-3 and n-6 PUFAs with NPs. SUBJECTS/METHODS: A cross-sectional analysis of the association between serum n-3 and n-6 PUFAs with plasma N-terminal atrial (NT-proANP) and brain (NT-proBNP) NPs in a population-based sample of 985 men aged 46-65 years from Eastern Finland. RESULTS: After adjustment for age and examination year, only serum n-6 PUFA arachidonic acid (ARA) was inversely associated with NT-proANP (P-trend across quartiles=0.02), but further adjustments for conventional risk factors (body mass index, smoking, alcohol intake, systolic blood pressure, low-density lipoprotein cholesterol and history of CVD) attenuated the association (P-trend=0.10). The associations with the other PUFAs were not statistically significant. Among the PUFAs, only serum n-3 PUFA docosapentaenoic acid (DPA; P-trend=0.03) and ARA (P-trend=0.02) had inverse associations with NT-proBNP after adjustment for age and examination years. The associations were again attenuated after further adjustments but remained statistically significant for DPA (P-trend=0.05). Our results also suggested that the inverse associations may be more evident among those using beta-blockers. CONCLUSIONS: Our study suggests little overall impact of serum n-3 or n-6 PUFAs on plasma NPs.

Prevalence of Obstructive Sleep Apnoea Among Patients Admitted for Bariatric Surgery. A Prospective Multicentre Trial.

BACKGROUND: Obesity has become one of the greatest public health concerns worldwide and is known to be the most important risk factor for obstructive sleep apnoea (OSA). Prevalence of OSA has increased over the last two decades, but it is estimated that the majority of cases still remain undiagnosed. The aim of this study was to investigate the prevalence of OSA in Finnish bariatric surgery candidates. METHODS: In this prospective multicentre study, standard overnight cardiorespiratory recording was conducted in 197 consecutive patients from three different hospitals. A sleep questionnaire was also administered. Anthropometric and demographic measurements included age, weight, body mass index (BMI) and waist and neck circumference. RESULTS: Altogether, 71 % of the patients were diagnosed with OSA. The prevalence was higher in males (90 %) than in females (60 %) (p < 0.001). In OSA patients' group, the mean neck and waist circumference was larger (p < 0.001) and the body weight higher (p < 0.01) than in non-OSA group. When separating patients by gender, a significant difference remained only concerning neck circumference in female patients. CONCLUSIONS: OSA is very common among bariatric surgery patients, especially in men. Considering this and the increased long-term morbidity and mortality generally related to OSA, a routine screening for OSA seems indicated in bariatric patients, particularly men.

The professional role of a dental hygienist in Finland - educators' views.

OBJECTIVES: To assess the role and envisioned professional identity of the dental hygienist in the eyes of their educators at the Finnish training institutes and to determine the need for any changes and improvements. METHODS: A cross-sectional explorative study used as its main method interviews conducted in 2012-2013 among educators of dental hygienists in Finland. Leading representatives of dental hygienist training at all vocational health institutes, dental schools and centres of health education were asked to participate in the study. The interviews consisted of two parts: a self-administered questionnaire and a semi-structured interview. The qualitative data were analysed with thematic analysis. The inductive theoretical approach served to categorize the data based on emergent themes and patterns. RESULTS: The educators held a general respect and appreciation for the dental hygienist profession. They felt that dental hygienists' skills ought to see more use in orthodontics and in preventive care than is customary today, including in tobacco prevention and smoking cessation as well as in dietary instruction among adults. The traditional role of the dental hygienist and the evolving scope of dental practice seemed mismatched. Concern about the lack of clarity regarding the division of labour in clinical practice was expressed. The respondents were convinced of that the division of labour in the public sector differs from that in the private sector. CONCLUSION: The educators thought that the role of the dental hygienist and the evolving scope of dental practice were partly mismatched. A reassessment of stakeholder involvement in the development of training curricula is urgently needed.

Oligoclonal bands in multiple sclerosis reactive against two herpesviruses and association with magnetic resonance imaging findings.

BACKGROUND: Two human herpesviruses, human herpesvirus 6 (HHV-6), and Epstein-Barr virus (EBV), have been repeatedly linked to multiple sclerosis (MS). OBJECTIVE: The aim of this study was to investigate HHV-6 and EBV reactive oligoclonal bands (OCBs), and viral DNA in the intrathecal compartment in MS. METHODS: The reactivity of OCBs in cerebrospinal fluid (CSF) for EBV and HHV-6 antigens and stability of virus reactive OCBs over time were studied in a well-characterized MS patient cohort. Associations between virus reactive OCBs and viral DNA in CSF (and any clinical and/or radiological findings) were investigated. RESULTS: Of patients with MS, 38% had OCBs reactive to either one of the viruses studied, compared to none in the patients with other inflammatory neurological diseases (p=0.005). The banding pattern of virus reactive OCBs remained the same over time. Furthermore, MS patients with viral DNA in CSF had more contrast enhancing lesions (CELs). CONCLUSION: The stable presence of herpesvirus reactive OCBs in CSF further strengthens the association of MS with these viruses. The finding that herpesviruses might be linked to the appearance of active lesions warrants investigation of new therapeutic strategies to treat these viruses in MS.

Tobacco use among Iranian dental students: a national survey.

A national survey was conducted to provide up-to-date data on current and ever use of tobacco among Iranian dental students. All 4th-year students of 8 randomly selected dental schools were surveyed anonymously in December 2010 using the Global Health Professions Student Survey questionnaire. Of 325 participants, 54.2% were ever users of tobacco products (73.0% of males versus 44.4% of females); 50.8% had used waterpipes, 34.2% cigarettes and 9.3% other products. The most common age at first use was 20-24 years for both sexes. Current tobacco use was reported by 20.6% of respondents, cigarette smoking by 10.8% and waterpipe smoking by 15.8%. Regression models showed that current cigarette and waterpipe smoking were significantly associated with male sex but not with type of dental school (state/private). Current waterpipe smoking was also associated with age at first experience. In view of the important role of dentists in tobacco control, the prevention of tobacco use should be stressed among Iranian dental students.

The relationship between cardiac and liver iron evaluated by MR imaging in haematological malignancies and chronic liver disease.

Although iron overload is clinically significant, only limited data have been published on iron overload in haematological diseases. We investigated cardiac and liver iron accumulation by magnetic resonance imaging (MRI) in a cohort of 87 subjects who did not receive chelation, including 59 haematological patients. M-HIC (MRI-based hepatic iron concentration, normal values <36 µmol/g) is a non-invasive, liver biopsy-calibrated method to analyse iron concentration. This method, calibrated to R2 (transverse relaxation rate), was used as a reference standard (M-HIC(R2)). Transfusions and ferritin were evaluated. Mean M-HIC(R2) and cardiac R(*) of all patients were 142 µmol/g (95% CI, 114-170) and 36.4 1/s (95% CI, 34.2-38.5), respectively. M-HIC(R2) was higher in haematological patients than in patients with chronic liver disease or normal controls (P<0.001). Clearly elevated cardiac R2(*) was found in two myelodysplastic syndrome (MDS) patients with severe liver iron overload. A poor correlation was found between liver and cardiac iron (n=82, r=0.322, P=0.003), in contrast to a stronger correlation in MDS (n=7, r=0.905, P=0.005). In addition to transfusions, MDS seemed to be an independent factor in iron accumulation. In conclusion, the risk for cardiac iron overload in haematological diseases other than MDS is very low, despite the frequently found liver iron overload.

Lysophosphatidic acid and sphingosine-1-phosphate promote morphogenesis and block invasion of prostate cancer cells in three-dimensional organotypic models.

Normal prostate and some malignant prostate cancer (PrCa) cell lines undergo acinar differentiation and form spheroids in three-dimensional (3-D) organotypic culture. Acini formed by PC-3 and PC-3M, less pronounced also in other PrCa cell lines, spontaneously undergo an invasive switch, leading to the disintegration of epithelial structures and the basal lamina, and formation of invadopodia. This demonstrates the highly dynamic nature of epithelial plasticity, balancing epithelial-to-mesenchymal transition against metastable acinar differentiation. This study assessed the role of lipid metabolites on epithelial maturation. PC-3 cells completely failed to form acinar structures in delipidated serum. Adding back lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) rescued acinar morphogenesis and repressed invasion effectively. Blocking LPA receptor 1 (LPAR1) functions by siRNA (small interference RNA) or the specific LPAR1 inhibitor Ki16425 promoted invasion, while silencing of other G-protein-coupled receptors responsive to LPA or S1P mainly caused growth arrest or had no effects. The G-proteins Gα(12/13) and Gα(i) were identified as key mediators of LPA signalling via stimulation of RhoA and Rho kinases ROCK1 and 2, activating Rac1, while inhibition of adenylate cyclase and accumulation of cAMP may be secondary. Interfering with these pathways specifically impeded epithelial polarization in transformed cells. In contrast, blocking the same pathways in non-transformed, normal cells promoted differentiation. We conclude that LPA and LPAR1 effectively promote epithelial maturation and block invasion of PrCa cells in 3-D culture. The analysis of clinical transcriptome data confirmed reduced expression of LPAR1 in a subset of PrCa's. Our study demonstrates a metastasis-suppressor function for LPAR1 and Gα(12/13) signalling, regulating cell motility and invasion versus epithelial maturation.

Iron overload: accuracy of in-phase and out-of-phase MRI as a quick method to evaluate liver iron load in haematological malignancies and chronic liver disease.

OBJECTIVES: The purpose of this prospective study was to evaluate the accuracy of in-phase and out-of-phase imaging to assess hepatic iron concentration in patients with haematological malignancies and chronic liver disease. METHODS: MRI-based hepatic iron concentration (M-HIC, µmol g(-1)) was used as a reference standard. 42 patients suspected of having iron overload and 12 control subjects underwent 1.5 T in- and out-of-phase and M-HIC liver imaging. Two methods, semi-quantitative visual grading made by two independent readers and quantitative relative signal intensity (rSI) grading from the signal intensity differences of in-phase and out-of-phase images, were used. Statistical analyses were performed using the Spearman and Kruskal-Wallis tests, receiver operator curves and κ coefficients. RESULTS: The correlations between M-HIC and visual gradings of Reader 1 (r = 0.9534, p < 0.0001) and Reader 2 (r = 0.9456, p < 0.0001) were higher than the correlations of the rSI method (r = 0.7719, p < 0.0001). There was excellent agreement between the readers (weighted κ = 0.9619). Both visual grading and rSI were similar in detecting liver iron overload: rSI had 84.85% sensitivity and 100% specificity; visual grading had 85% sensitivity and 100% specificity. The differences between the grades of visual grading were significant (p < 0.0001) and the method was able to distinguish different degrees of iron overload at the threshold of 151 µmol g(-1) with 100% positive predictive value and negative predictive value. CONCLUSION: Detection and grading of liver iron can be performed reliably with in-phase and out-of-phase imaging. Liver fat is a potential pitfall, which limits the use of rSI.

Systematic knockdown of epigenetic enzymes identifies a novel histone demethylase PHF8 overexpressed in prostate cancer with an impact on cell proliferation, migration and invasion.

Our understanding of key epigenetic regulators involved in specific biological processes and cancers is still incomplete, despite great progress in genome-wide studies of the epigenome. Here, we carried out a systematic, genome-wide analysis of the functional significance of 615 epigenetic proteins in prostate cancer (PrCa) cells. We used the high-content cell-spot microarray technology and siRNA silencing of PrCa cell lines for functional screening of cell proliferation, survival, androgen receptor (AR) expression, histone methylation and acetylation. Our study highlights subsets of epigenetic enzymes influencing different cancer cell phenotypes. Plant homeo domain (PHD) finger proteins have a key role in cell survival and histone methylation, whereas histone deacetylases were primarily involved in regulating AR expression. In contrast, JumonjiC-domain (JmjC) containing histone lysine demethylases (KDMs) mainly had an impact on cell proliferation. Our results show that the KDMs JARID1B, PHF8, KDM3A, KDM3B and KDM4A were highly expressed in clinical PrCa samples. The PHD-finger protein 8 (PHF8), a transcriptional coactivator with both PHD- and JmjC-domains, was moderately to strongly expressed in 80% of clinical PrCa samples, whereas 76% of normal and benign samples were negative or only showed weak PHF8 expression. Strong PHF8 expression correlated significantly with high Gleason grade and was borderline significant for poor prognosis. The results of functional PHF8 knockdown implicate a role in cell migration and invasion, as shown by cell motility and 3-D invasion assays. Our study suggests that various cellular phenotypes are regulated by distinct subsets of epigenetic enzymes. Proteins interpreting and modifying histone methylation, such as JmjC-domain and particularly PHD-finger proteins like PHF8, are activated in subsets of PrCa's and promote cancer relevant phenotypes.

Smoking and its determinants among Iranian dental students.

OBJECTIVE: The objective of the present study was to investigate smoking habits of Iranian dental students in relation to their background characteristics and oral self-care (OSC). SUBJECTS AND METHODS: A survey in the form of a questionnaire was conducted of 327 senior dental students in seven randomly selected state dental schools in Iran. In addition to smoking habits and background characteristics, the students were asked about OSC. A recommended level of OSC was defined as a combination of brushing at least twice a day, frequent use of fluoridated toothpaste, and eating sugary snacks less than daily. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A total of 263 students (113 males and 150 females) completely answered the questions and were included in the analyses. RESULTS: Of the 263 students, 59 (23%, 37 males and 22 females) reported current smoking (cigarette, pipe, or water pipe). Current smoking was associated with male gender (OR = 2.9, 95% CI = 1.4-5.6), level of father's education (OR = 1.4, 95% CI = 1.1-1.8), and OSC (OR = 4.4, 95% CI = 1.3-14.9). CONCLUSION: Smoking among Iranian dental students is similar to their socioeconomic group, and is associated with the characteristics of their background, such as gender and father's level of education, as well as the quality of OSC. The results indicate a need to include smoking cessation education and public health activities in the dental curriculum to provide future health care professionals and role models for patients with adequate training in up-to-date patient management to control smoking.

Early thrombin generation and impaired fibrinolysis after SCT associate with acute GVHD.

The evolution of coagulation and fibrinolysis has not been thoroughly evaluated in allogeneic SCT. In this pilot study, we characterized the adaptive mechanisms of coagulation and fibrinolysis during allogeneic SCT and 3-month follow-up and studied possible associations with outcome, including acute GVHD. Thirty patients underwent SCT for a haematological malignancy after myeloablative conditioning. Nineteen patients received the transplant from an HLA-identical sibling and 11 from an unrelated donor. GVHD prophylaxis consisted of CYA and MTX, with methylprednisolone in sibling transplants. Serial coagulation and fibrinolytic activity markers were assessed, including prothrombin fragments 1+2 (F1+2), thrombin time, D-dimer, tissue-type plasminogen-activator (tPA) and plasminogen-activator inhibitor (PAI-1). Early during conditioning therapy, F1+2 and D-dimer increased threefold indicating thrombin generation and fibrin turnover. TPA activity peaked before engraftment, concurring with diminished PAI-1. At 10 days after transplantation shortened thrombin time (<15 s), F1+2 exceeding 0.7 nmol/L and PAI-1 3.0 IU/mL were associated with the development of GVHD. In conclusion, early maladaptation, that is, upregulated thrombin generation and inhibition of fibrinolysis, occurred in one-third of the SCT patients associating with the development of GVHD, a finding suggesting an interplay between coagulation and immunology during SCT.

A cluster randomised trial of effectiveness of educational intervention in primary health care on early childhood caries.

Early childhood caries (ECC) remains a serious problem in several developing and developed countries. This cluster randomised trial evaluated the impact of a 6-month educational intervention on ECC. The trial targeted 12- to 15-month-old children (n = 242) and their mothers in Tehran, Iran, visiting 18 public health centres, randomly selected and assigned to two intervention groups and one control group. At baseline, each mother was interviewed and each child underwent a dental examination of all teeth for the number of decayed teeth (dt) and of upper central incisors for the number of teeth with enamel caries (de). All mothers in the two intervention groups (A and B) received oral health instructions from the vaccination staff. In addition, group A received extra reminders. The outcome was defined as increments in the number of teeth with dt or de, as percentages of children developing new dt or de, and as the number needed to treat (NNT). No new de appeared in group A, the mean de increment in group B was 0.2 (SD = 0.6), and in the controls, it was 0.4 (SD = 0.7) (p < 0.05). The percentages of children developing new de were 0, 14, and 26%, respectively. No differences in dt increments were found. Regarding de, NNT for group A was 4 and for B 9; the figures for dt were 13 and 17, respectively. In conclusion, oral health education given to mothers by general health staff is a valuable tool to prevent caries in infants and toddlers.

Oral health behaviour of Iranian mothers and their 9-year-old children.

PURPOSE: The present study examined associations between the oral health behaviour (OHB) of Iranian mothers and the OHB and oral health status of their children. MATERIALS AND METHODS: In 2005, two self-administered questionnaires provided data on the OHB of a random sample of 9-year-old children (n = 459) and their mothers in Tehran, Iran. Brushing frequency, use of fluoridated toothpaste and number of sugary snacks between meals served as oral self-care (OSC) assessment criteria for both. A clinical examination was performed for children at school. DMFT/dmft values, the restoration index (RI) and the unmet treatment needs index (UTN) facilitated an assessment of children's dental status and treatment. Chi-square test, bivariate correlation, and binary logistic regression model were employed in these analyses. RESULTS: Mother's OSC correlated with child's OSC (r = 0.18; p < 0.01). The reported children's brushing frequency correlated with mothers' brushing frequency (r = 0.2; p < 0.01). High maternal OSC levels were associated with lower dental treatment (DT) values in children (p < 0.01). Children's RI was positively and UTN negatively associated with mothers' OSC (p < 0.01). In the model, mothers' OSC (OR = 2.1) and female gender (OR = 2.1) were associated with children's OSC, while mothers' OSC was strongly associated with DT (OR = 11.0) and RI (OR = 34.0) in children. CONCLUSIONS: Higher OSC levels of the surveyed mothers were reflected positively in the oral health status and behaviour of their offspring. The potential of mothers to play a significant role in the oral health of their children should be kept in mind when developing oral health promotion programmes.

Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

OBJECTIVE: Based on case-control and prospective studies elevated blood total homocysteine (tHcy) has been suggested to be an independent risk factor for cardiovascular diseases (CVD). The purpose of the study was to explore the joint effect of increased serum tHcy concentration and other risk factors on the risk of CVD mortality in middle-aged men without a history of heart disease or stroke. DESIGN: A prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. SETTING: Eastern Finland. Subjects. A total of 802 men aged 46-64 years, examined in 1991-93. MAIN OUTCOME MEASURES: CVD mortality event. RESULTS: The mean serum tHcy concentration was 10.8 micromol L(-1) (SD 3.3). During the average follow-up time of 10.8 years 50 men experienced a CVD death. The hazard rate ratio for CVD mortality was 1.80 (95% confidence interval: 1.02-3.19) in men in the highest serum tHcy third versus lower thirds after adjustment for cardiovascular risk factors. Furthermore, elevated serum tHcy concentration appeared to increase the risk of CVD death in men who smoke or who have high circulating concentrations of serum total or LDL cholesterol, apo-B apolipoprotein or plasma fibrinogen. CONCLUSION: We conclude that homocysteine may increase the risk of CVD mortality in middle-aged men from Eastern Finland, and it may especially increase the risk when present with other risk factors for CVD.

Dysphagia and oesophageal clearance after laparoscopic versus open Nissen fundoplication. A randomized, prospective trial.

BACKGROUND: An increase in postoperative dysphagia has been reported after laparoscopic fundoplication. Our aim was to compare laparoscopic Nissen-Rossetti fundoplication to open fundoplication regarding oesophageal clearance and dysphagia in a prospective, randomized study. METHODS: Twenty-eight consecutive patients with objectively observed gastro-oesophageal reflux disease referred to operative treatment were randomized to laparoscopic (13) or open (15) fundoplication. A standard formula was used in pre- and postoperative interview. Oesophageal clearance was measured by liquid bolus radionuclide transit before and 3 days, 1 month and 1 year after fundoplication. Endoscopy was done preoperatively and 1 year after the operation. RESULTS: Heartburn, regurgitation and ooesophagitis were cured with equal effectiveness (p = 0.001). New-onset dysphagia was observed in nine (69%) of the patients in the laparoscopic group and in nine (60%) in the open group during the first postoperative month. Food impaction occurred in four (31%) cases after laparoscopic and in two (13%) after open surgery (ns). One year after the operation, one patient (8%) in both groups had more than mild symptoms. Oesophageal radionuclide transit remained normal after open fundoplication, but after the laparoscopic procedure oesophageal clearance was disturbed--only one patient did not have a pathologic result during the first postoperative month. One year after the operation, clearance was normal. CONCLUSIONS: After laparoscopic operation, a tendency to more severe new-onset dysphagia was observed, and oesophageal clearance was transiently disturbed. Efforts should be made to minimize postoperative swallowing and clearance disturbances after laparoscopic fundoplication in order to get the full value out of otherwise more rapid recovery.