Does ischemic preconditioning require reperfusion before index ischemia?

Abstract:
BACKGROUND Ischemic preconditioning (IP) is initiated through one or several short bouts of ischemia and reperfusion which precede a prolonged ischemia. To test whether a reperfusion must precede the prolonged index ischemia, a series without reperfusion (intraischemic preconditioning: IIP) and a series with gradual onset of ischemia, i.e. ramp ischemia (RI), which is possibly related to the development of hibernation, was compared to conventional IP (CIP).
METHOD Experiments were performed an 27 blood-perfused rabbit hearts (Langendorff apparatus) that were randomized into one of four series: (1) control (n = 7): 60 min normal flow - 60 min low flow (10%) ischemia - 60 min reperfusion. (2) CIP (n = 7): 4 times 5 min zero flow with 10 min reperfusion each - 60 min low flow (10%) - ischemia 60 min reperfusion. (3) IIP (n = 7): 50 min normal flow - 10 min no flow - 60min low flow (10%) ischemia -4 60min reperfusion. (4) RI (n=6): gradual reduction to 10% flow during 60min - 60min low flow (10%) ischemia - 60min reperfusion. At the end of each protocol, the infarcted area was assessed.
RESULTS The infarct area in control hearts was 6.7+/-1.4% (means+/-SEM) of LV total area, in CIP hearts 2.6+/-0.8%, in IIP hearts 3.1+/-0.5%, and in RI hearts 3.0+/-0.3% (all p<0.05 vs. control). The differences between the three protection protocols were statistically not significant, and no protective protocol reduced post-ischemic myocardial dysfunction.
CONCLUSION The preconditioning effect (infarct size reduction) appears not to depend on intermittent reperfusion. Thus, the protective mechanism of IP develops during the initial ischemia that precedes the index ischemia. Alternatively, low-flow ischemia is effectively a sort of reperfusion.


Are sports medicine journals relevant and applicable to practitioners and athletes?

Abstract:
OBJECTIVE To examine the evidence base of sports medicine research and assess how relevant and applicable it is to everyday practice.
METHODS Original research articles, short reports, and case reports published in four major sport and exercise medicine journals were studied and classified according to the main topic of study and type of subjects used.
RESULTS The most common topic was sports science, and very few studies related to the treatment of injuries and medical conditions. The majority of published articles used healthy subjects sampled from the sedentary population, and few studies have been carried out on injured participants.
CONCLUSION There is a dearth of studies addressing diagnostic and treatment interventions in the sports medicine literature. The evidence base for sports medicine must continue to increase in terms of volume and quality.


Are polymorphisms in oestrogen receptors genes associated with lipid levels in response to hormone therapy?

Abstract:
BACKGROUND Polymorphisms in the oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2) genes are associated with intermediate or endpoint markers of cardiovascular disease and with the efficacy of postmenopausal hormone therapy (HT). Contradictory findings have been described in the past and the role of these genetics variants remains unclear.
METHODS A cross-sectional study was carried out with 266 postmenopausal women, of whom 115 received oral HT (HT+) and 151 did not receive any HT (HT-). We analysed three single-nucleotide polymorphisms (SNPs) in ESR1 (rs1801132, rs7757956 and rs2813544) and two in ESR2 (rs3020450 and rs7154455) and derived haplotypes with three additional polymorphisms that had been previously investigated by our group (ESR1 rs2234693 and ESR2 rs1256049 and rs4986938).
RESULTS The ESR1 rs2813544 polymorphism was associated with low-density lipoprotein cholesterol (LDL-C) in HT+ postmenopausal women (p = 0.044; pC = 0.388), while one ESR2 gene haplotype was associated with total cholesterol (T-chol) (p = 0.015; pC = 0.090) and LDL-C in HT+ postmenopausal women (p = 0.021; pC = 0.126).
CONCLUSION Our findings suggest that, in HT+ postmenopausal women, the rs2813544 polymorphism may influence LDL-C levels and, as previously described, ESR2 rs1256049 is associated with T-chol and LDL-C. No previous study has investigated the association of this SNP set with lipoprotein levels in women while taking into account the hormonal status of the patients.


Sternal plating for primary and secondary sternal closure; can it improve sternal stability?

Abstract:
BACKGROUND Sternal instability with mediastinitis is a very serious complication after median sternotomy. Biomechanical studies have suggested superiority of rigid plate fixation over wire cerclage for sternal fixation. This study tests the hypothesis that sternal closure stability can be improved by adding plate fixation in a human cadaver model.
METHODS Midline sternotomy was performed in 18 human cadavers. Four sternal closure techniques were tested: (1) approximation with six interrupted steel wires; (2) approximation with six interrupted cables; (3) closure 1 (wires) or 2 (cables) reinforced with a transverse sternal plate at the sixth rib; (4) Closure using 4 sternal plates alone. Intrathoracic pressure was increased in all techniques while sternal separation was measured by three pairs of sonomicrometry crystals fixed at the upper, middle and lower parts of the sternum until 2.0 mm separation was detected. Differences in displacement pressures were analyzed using repeated measures ANOVA and Regression Coefficients.
RESULTS Intrathoracic pressure required to cause 2.0 mm separation increased significantly from 183.3 +/- 123.9 to 301.4 +/- 204.5 in wires/cables alone vs. wires/cables plus one plate respectively, and to 355.0 +/- 210.4 in the 4 plates group (p<0.05). Regression Coefficients (95% CI) were 120 (47-194) and 142 (66-219) respectively for the plate groups.
CONCLUSION Transverse sternal plating with 1 or 4 plates significantly improves sternal stability closure in human cadaver model. Adding a single sternal plate to primary closure improves the strength of sternal closure with traditional wiring potentially reducing the risk of sternal dehiscence and could be considered in high risk patients.


Can dose reduction to one parotid gland prevent xerostomia?

Abstract:
AIMS Dryness of the mouth is one of the most distressing chronic toxicities of radiation therapy in head and neck cancers. In this study, parotid function was assessed in patients with locally advanced head and neck cancers undergoing intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Parotid function was assessed with the help of a questionnaire and parotid scintigraphy, especially with regards to unilateral sparing of the parotid gland.
MATERIALS AND METHODS In total, 19 patients were treated with compensator-based IMRT between February 2003 and March 2004. The dose to the clinical target volume ranged between 66 and 70 Gy in 30-35 fractions to 95% of the isodose volume. Ipsilateral high-risk neck nodes received an average dose of 60 Gy and the contralateral low-risk neck received a dose of 54-56 Gy. Eight of 19 patients also received concomitant chemotherapy.
RESULTS Subjective toxicity to the parotid glands was assessed with the help of a questionnaire at 0, 3 and 6 months and objective toxicity was assessed with parotid scintigraphy at 0 and 3 months. The mean dose to the ipsilateral parotid gland ranged from 19.5 to 52.8 Gy (mean 33.14 Gy) and the mean dose to the contralateral gland was 11.1-46.6 Gy (mean 26.85 Gy). At a median follow-up of 13 months, 9/19 patients had no symptoms of dryness of the mouth (grade I), 8/19 had mild dryness of the mouth (grade II) and only 2/19 had grade III xerostomia, although the parotid gland could only be spared on one side in most of the patients.
CONCLUSION Minimising the radiation dose to one of the parotid glands with the help of IMRT in patients with advanced head and neck cancers can prevent xerostomia in most patients and parotid scintigraphy is a useful method of documenting xerostomia.


Increased neutrophil migratory activity after major trauma: a factor in the etiology of acute respiratory distress syndrome?

Abstract:
OBJECTIVE Neutrophil infiltration of the lung is characteristic of early posttraumatic acute respiratory distress syndrome (ARDS). This study examines the ability of neutrophils isolated (over the first 24 hrs) from the peripheral blood of patients admitted after major trauma to migrate in response to interleukin-8. Interleukin-8 is elevated in the lung within 2 hrs of major trauma in patients who later develop ARDS, and thus it plays a central role in the recruitment of neutrophils to the lung and their subsequent activation. We hypothesized that enhanced interleukin-8-mediated neutrophil migratory activity in the early postinjury phase, before the development of ARDS, may be a crucial factor in the etiology of ARDS.
DESIGN Prospective observational study.
SETTING University Hospital Wales, the Royal Gwent Hospital, and East Glamorgan General Hospital. Laboratory work was conducted at the Institute of Nephrology.
PATIENTS Adult blunt trauma victims with Injury Severity Score>or = 18.
MEASUREMENTS AND MAIN RESULTS Neutrophils were isolated from citrated blood from 17 adult blunt major trauma patients at admission (0 hrs) and 8 and 24 hrs later. Identical samples were obtained from normal laboratory volunteers (n = 9). The neutrophil count in each specimen was measured, and the number of neutrophils migrating across porous tissue culture inserts in response to defined concentrations of interleukin-8 (0, 10, 30, and 100 ng/mL) was quantitated by peroxidase assay. Neutrophil counts in the whole blood specimens obtained from those later developing ARDS were elevated significantly at admission and declined rapidly throughout the next 24 hrs. Significantly greater numbers of trauma patients' neutrophils migrated to concentrations of interleukin-8 (30 and 100 ng/mL) at each time point when compared with normal volunteers (Mann-Whitney U test, p<.05). Neutrophils isolated from major trauma patients exhibited an enhanced migratory response to high concentrations of interleukin-8 throughout the first 24 hrs of admission, in contrast to the normal physiologic attenuation of migration seen in neutrophils isolated from normal laboratory volunteers.
CONCLUSION These data indicate that major blunt trauma enhances the migratory capacity of circulating neutrophils. This is manifest within 2 hrs of admission and may be attributable to alteration in interleukin-8 receptor expression, affinity, or downstream signaling. In patients who later develop ARDS, initially elevated circulating neutrophil counts decrease rapidly, over the same time course. Early enhanced neutrophil migratory activity coupled with elevated pulmonary concentrations of interleukin-8 may be central to the establishment of the neutrophil infiltration that is characteristic of ARDS.


Does higher body mass index contribute to worse asthma control in an urban population?

Abstract:
BACKGROUND Epidemiologic findings support a positive association between asthma and obesity.
OBJECTIVE Determine whether obesity or increasing level of body mass index (BMI) are associated with worse asthma control in an ethnically diverse urban population.
METHODS Cross-sectional assessment of asthma control was performed in patients with asthma recruited from primary care offices by using 4 different validated asthma control questionnaires: the Asthma Control and Communication Instrument (ACCI), the Asthma Control Test (ACT), the Asthma Control Questionnaire (ACQ), and the Asthma Therapy Assessment Questionnaire (ATAQ). Multiple linear regression analysis was performed to evaluate the association between obesity and increasing BMI level and asthma control.
RESULTS Of 292 subjects with a mean age of 47 years, the majority were women (82%) and African American (67%). There was a high prevalence of obesity with 63%, with only 15% normal weight. The mean score from all 4 questionnaires showed an average suboptimal asthma control (mean score/maximum possible score): ACCI (8.3/19), ACT (15.4/25), ACQ (2.1/6), and ATAQ (1.3/4). Regression analysis showed no association between obesity or increasing BMI level and asthma control using all 4 questionnaires. This finding persisted even after adjusting for FEV(1), smoking status, race, sex, selected comorbid illnesses, and long-term asthma controller use.
CONCLUSION Using 4 validated asthma control questionnaires, we failed to find an association between obesity and asthma control in an urban population with asthma. Weight loss may not be an appropriate strategy to improve asthma control in this population.


Does a physician's specialty influence the recording of medication history in patients' case notes?

Abstract:
AIMS To determine the impact of a physician's specialty on the frequency and depth of medication history documented in patient medical records.
METHODS A cross-sectional assessment of the frequency and depth of medication history information documented by 123 physicians for 900 randomly selected patients stratified across Cardiology, Chest, Dermatology, Endocrine, Gastroenterology, Haematology, Neurology, Psychiatry and Renal specialties was carried out at a 900-bed teaching hospital located in Ibadan, Nigeria.
RESULTS Four hundred and forty-three (49.2%) of the cohort were males and 457 (50.8%) were females; with mean ages 43.2 +/- 18.6 and 43.1 +/- 17.9 years respectively. Physicians' specialties significantly influenced the depth of documentation of the medication history information across the nine specialties (P<0.0001). Post hoc pair-wise comparisons with Tukey's HSD test showed that the mean scores for adverse drug reactions and adherence to medicines was highest in the Cardiology specialty; while the Chest specialty had the highest mean scores for allergy to drugs, food, chemicals and cigarette smoking. Mean scores for the use of alcohol; illicit drugs; dietary restrictions was highest for Gastroenterology, Psychiatry and Endocrine specialties respectively. Physicians' specialties also significantly influenced the frequency of documentation of the medication history across the nine specialties (P<0.0001).
CONCLUSION Physicians appear to document more frequently and in greater depth medication history information that may aid the diagnostic tasks in their specific specialty. Researchers and other users of medication history data documented in patients' medical records by physicians may want to take special cognizance of this phenomenon.


Living in an urban environment and non-communicable disease risk in Thailand: Does timing matter?

Abstract:
BACKGROUND This paper uses a life-course approach to explore whether the timing and/or duration of urban (vs rural) exposure was associated with risk factors for NCDs.
METHODS A cross-sectional survey was conducted among health care workers in two hospitals in Thailand. Two measures of urbanicity were considered: early-life urban exposure and the proportion of urban life years. We explored four behavioral NCD risk factors, two physiological risk factors and four biological risk factors.
RESULTS Both measures of urbanicity were each independently associated with increases in all behavioral and physiological risk factors. For some biological risk factors, people spending their early life in an urban area may be more susceptible to the effect of increasing proportion of urban life years than those growing up in rural areas.
CONCLUSION Urbanicity was associated with increases in behavioral and physiological risk factors. However, these associations may not translate directly into increases in biological risk factors. It is likely that these biological risk factors were results of a complex interaction between both long term accumulation of exposure and early life exposures.


Does a febrile reaction to platelets predispose recipients to red blood cell alloimmunization?

Abstract:
BACKGROUND A variable effect of inflammation on alloimmunization to transfused red blood cells (RBCs) in mice has been recently reported. We investigated whether RBC alloimmunization in humans was affected by transfusion of blood products in temporal proximity to experiencing a febrile transfusion reaction (FTR) to platelets (PLTs), an event predominantly mediated by inflammatory cytokines.
STUDY DESIGN AND METHODS Blood bank databases were used to identify patients who experienced an FTR or possible FTR to PLTs from August 2000 to March 2008 (FTR group). The control group of patients received a PLT transfusion on randomly selected dates without experiencing an FTR. The "event" was defined as the PLT transfusion that caused the FTR in the FTR group or the index PLT transfusion in the control group. The number of transfused blood products and their proximity to the event were recorded along with other recipient data. The primary endpoint was the rate of RBC alloimmunization between the two groups.
RESULTS There were 190 recipients in the FTR group and 245 in the control group. Overall, the recipients in the control group were younger and received more blood products on the day of their event and over the subsequent 10 days. The alloimmunization rate among recipients in the FTR group was higher than in the control group (8% vs. 3%, respectively; p = 0.026).
CONCLUSION These preliminary data support our hypothesis that recipient inflammation may affect RBC alloimmunization in humans; however, a more detailed understanding of the pathophysiologic association between inflammation and alloimmunization is required before definitive conclusions can be reached.


Maternal creatine homeostasis is altered during gestation in the spiny mouse: is this a metabolic adaptation to pregnancy?

Abstract:
BACKGROUND Pregnancy induces adaptations in maternal metabolism to meet the increased need for nutrients by the placenta and fetus. Creatine is an important intracellular metabolite obtained from the diet and also synthesised endogenously. Experimental evidence suggests that the fetus relies on a maternal supply of creatine for much of gestation. However, the impact of pregnancy on maternal creatine homeostasis is unclear. We hypothesise that alteration of maternal creatine homeostasis occurs during pregnancy to ensure adequate levels of this essential substrate are available for maternal tissues, the placenta and fetus. This study aimed to describe maternal creatine homeostasis from mid to late gestation in the precocial spiny mouse.
METHODS Plasma creatine concentration and urinary excretion were measured from mid to late gestation in pregnant (n = 8) and age-matched virgin female spiny mice (n = 6). At term, body composition and organ weights were assessed and tissue total creatine content determined. mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and the creatine transporter (CrT1) were assessed by RT-qPCR. Protein expression of AGAT and GAMT was also assessed by western blot analysis.
RESULTS Plasma creatine and renal creatine excretion decreased significantly from mid to late gestation (P<0.001, P<0.05, respectively). Pregnancy resulted in increased lean tissue (P<0.01), kidney (P<0.01), liver (P<0.01) and heart (P<0.05) mass at term. CrT1 expression was increased in the heart (P<0.05) and skeletal muscle (P<0.05) at term compared to non-pregnant tissues, and creatine content of the heart (P<0.05) and kidney (P<0.001) were also increased at this time. CrT1 mRNA expression was down-regulated in the liver (<0.01) and brain (<0.01) of pregnant spiny mice at term. Renal AGAT mRNA (P<0.01) and protein (P<0.05) expression were both significantly up-regulated at term, with decreased expression of AGAT mRNA (<0.01) and GAMT protein (<0.05) observed in the term pregnant heart. Brain AGAT (<0.01) and GAMT (<0.001) mRNA expression were also decreased at term.
CONCLUSION Change of maternal creatine status (increased creatine synthesis and reduced creatine excretion) may be a necessary adjustment of maternal physiology to pregnancy to meet the metabolic demands of maternal tissues, the placenta and developing fetus.


Pap smears with glandular cell abnormalities: Are they detected by rapid prescreening?

Abstract:
BACKGROUND Rapid prescreening (RPS) is one of the quality assurance (QA) methods used in gynecologic cytology. The efficacy of RPS has been previously studied but mostly with respect to squamous lesions; in fact, there has been no study so far specifically looking at the sensitivity of RPS for detecting glandular cell abnormalities.
METHODS A total of 80,565 Papanicolaou (Pap) smears underwent RPS during a 25-month period. A sample was designated as "review for abnormality" (R) if any abnormal cells (at the threshold of atypical squamous cells of undetermined significance/atypical glandular cells [AGC]) were thought to be present or was designated as negative (N) if none were detected. Each sample then underwent full screening (FS) and was designated as either R or N and also given a cytologic interpretation.
RESULTS The final cytologic interpretation was a glandular cell abnormality (≥AGC) in 107 samples (0.13%); 39 of these (36.4%) were flagged as R on RPS. Twenty-four patients (33.8%) out of 71 who had histologic follow-up were found to harbor a high-grade squamous intraepithelial lesion or carcinoma; 13 of those 24 Pap smears (54.2%) had been flagged as R on RPS. Notably, 11 AGC cases were picked up by RPS only and not by FS and represented false-negative cases; 2 of these showed endometrial adenocarcinoma on histologic follow-up.
CONCLUSION Pap smears with glandular cell abnormalities are often flagged as abnormal by RPS, and this results in a sensitivity of 36.4% (at the AGC threshold). Most importantly, some cases of AGC are detected on Pap smears by RPS only, and this demonstrates that RPS is a valuable QA method.


The HELPP syndrome--evidence of a possible systemic inflammatory response in pre-eclampsia?

Abstract:
INTRODUCTION The principal causes of morbidity and mortality during pregnancy in Mexico, are preeclampsia/eclampsia, obstetric hemorrhage and puerperium complications; this is, 62% of maternal deaths in last years. HELLP syndrome was observed between 5 to 25% of the mortality in pregnancies of 36 weeks or less.
OBJECTIVE To analyze patients with HELLP syndrome in ICU's (Intensive Care Unit) of a Gynecology and Obstetric Hospital, related to the abnormal hematological, hepatic and renal results with the obstetric case history and the clinical complications.
MATERIALS AND METHODS A transversal study in patients with HELLP syndrome during 1998 and 1999 were carry out.
CASE DEFINITION Peripheral blood with Microangiopathic hemolysis, elevated liver enzymes: AST, ALT over 40 UI/L, even when were LDH lower than 600 UI/L. It was evaluated the hepatic and renal function, platelets count, microangiopathic hemolysis, arterial pressure, seizures, icteric skin color, blindness, visual disturbances, nausea, vomiting and upper quadrant right abdominal pain. In newborn we analyzed gestational age, sex, weight and APGAR. We studied for an association between maternal and biochemical variables with Correlation Pearson Test, and dependence between variables with lineal regression model.
RESULTS 2878 patients with hypertensives disorders in pregnancy (11.64%). The 1.15% (n = 33) had HELLP syndrome with specific maternal mortality of 0.4 per 10,000 live birth, perinatal mortality of 1.62 per 10,000 live birth; and renal damage in 84.5%. Coefficient beta was higher between number of pregnancies to platelets count (-0.33) and creatinine clearance (-0.401).
CONCLUSION We found an important renal damage, low platelets, elevated liver enzymes in women with two or more pregnancies. Then we propose there are similarities between HELLP syndrome and Systemic Inflammatory Response Syndrome (SIRS) because they could have the same pathophysiology.


Delayed peripheral facial palsy in the stapes surgery: can it be prevented?

Abstract:
PURPOSE The aim of this study was to evaluate poststapedectomy-delayed facial palsy etiopathogenesis, risk factors, evolution, and prevention.
MATERIALS AND METHODS Seven hundred six stapedectomies performed in 580 patients were reviewed. In all patients who developed delayed facial palsy, the dates of onset and subside of facial palsy, the anatomic and pathologic predisposing factors, and a possible history for recurrent labial herpetic lesions were considered. The House-Brackmann (H-B) grading system was used to evaluate the facial function. Virus-specific immunoglobulin (Ig) G and IgM antibodies against herpes simplex virus type 1 (HSV-1) were determined by enzyme-linked immunosorbent assay (ELISA) 3 weeks after the onset of the paralysis. The results were compared with a control group without a history of recurrent herpes labialis.
RESULTS Poststapedectomy facial palsy developed in 7 out of 706 procedures. All 7 patients referred a history of recurrent labial herpetic lesions. One patient showed a facial palsy H-B grade II, 2 a grade III, and 3 a grade IV. After acyclovir therapy, 6 subjects recovered completely, whereas 1 maintained an H-B grade II. An increased IgG antibody titer was found in 6 of the patients with delayed facial palsy and in 1 out of 7 controls. Mean IgG titer was 1:14,050 in the subjects with delayed facial palsy and 1:2,300 in controls (P<.001).
CONCLUSION Poststapedectomy-delayed facial palsy is likely caused by a reactivation of HSV-1, latent within the geniculate ganglion. The activation of the latent virus is more frequent in patients with a history of herpes labialis and can be prevented by an adequate acyclovir therapy.


Hepatic arterial embolization for unresectable hepatocellular carcinomas: do technical factors affect prognosis?

Abstract:
PURPOSE To evaluate retrospectively whether technical factors of hepatic arterial embolization affect the prognosis of patients with hepatocellular carcinoma (HCC).
MATERIALS AND METHODS Inclusion criteria of this study were the following: (1) patients received embolization as the initial treatment during 2003-2004, (2) Child A or B liver profile, (3) five or fewer HCCs with maximum diameter of 7 cm or smaller, and (4) no extrahepatic metastasis. Patient data were gathered from 43 centers. Prognostic factors were evaluated using univariate and multivariate analyses.
RESULTS Eight hundred fifteen patients were enrolled. The 1-, 3-, 5-, and 7-year overall survival rates were 92.0 % (95 % CI 90.1-93.9), 62.9 % (95 % CI 59.3-66.6), 39.0 % (95 % CI 35.1-43.0), and 26.7 % (95 % CI 22.6-30.8) in all patients. Univariate analysis showed a Child-Pugh class-A, alpha-fetoprotein level lower than 100 ng/ml, tumor size of 3 cm or smaller, tumor number of 3 or fewer, one-lobe tumor distribution, nodular tumor type, within the Milan criteria, stage I or II, no portal venous invasion, use of iodized oil, and selective embolization were significantly better prognostic factors. In the multivariate Cox model, the benefit to survival of selective embolization remained significant (hazard ratio 0.68; 95 % CI 0.48-0.97; p = 0.033).
CONCLUSION Selective embolization contributes to survival in patients with HCCs.


Can echocardiography and ECG discriminate hereditary transthyretin V30M amyloidosis from hypertrophic cardiomyopathy?

Abstract:
OBJECTIVE Hereditary transthyretin (ATTR) amyloidosis with increased left ventricular wall thickness could easily be misdiagnosed by echocardiography as hypertrophic cardiomyopathy (HCM). Our aim was to create a diagnostic tool based on echocardiography and ECG that could optimise identification of ATTR amyloidosis.
METHODS Data were analysed from 33 patients with biopsy proven ATTR amyloidosis and 30 patients with diagnosed HCM. Conventional features from ECG were acquired as well as two dimensional and Doppler echocardiography, speckle tracking derived strain and tissue characterisation analysis. Classification trees were used to select the most important variables for differentiation between ATTR amyloidosis and HCM.
RESULTS The best classification was obtained using both ECG and echocardiographic features, where a QRS voltage>30 mm was diagnostic for HCM, whereas in patients with QRS voltage<30 mm, an interventricular septal/posterior wall thickness ratio (IVSt/PWt)>1.6 was consistent with HCM and a ratio<1.6 supported the diagnosis of ATTR amyloidosis. This classification presented both high sensitivity (0.939) and specificity (0.833).
CONCLUSION Our study proposes an easily interpretable classification method for the differentiation between HCM and increased left ventricular myocardial thickness due to ATTR amyloidosis. Our combined echocardiographic and ECG model could increase the ability to identify ATTR cardiac amyloidosis in clinical practice.


Nasal polyposis: is there an inheritance pattern?

Abstract:
BACKGROUND Nasal Polyposis (NP) is defined as a chronic inflammatory disease of sinonasal mucosa leading to diffuse formation of benign polyps. Although family histories are frequently suggested in medical literature, no specific study focused on this point has been reported. The purpose of this study is to determine whether a hereditary factor could be implied for NP in a family where several members were affected. We included 99 members of this family.
METHODS All patients were assessed for conditions known to be associated with the development or presence of NP. Concerning NP, patients were screened with a validated questionnaire and selected patients had a medical examination by an Ear, Nose and Throat practitioner.
RESULTS Thirteen patients had a personal history of NP without asthma, aspirin intolerance, Churg Strauss syndrome, cystic fibrosis, Young's syndrome, bare lymphocyte syndrome, or primary ciliary dyskinesia. Within this family, 19.7% of those older than 17 years were affected by NP, as compared with the national French prevalence of 2.1%.
CONCLUSION Regarding the pedigree, we discuss different modes of inheritance. The presence of consanguineous unions in this family suggests the possibility of a common ancestor and thus a recessive autosomal mode of inheritance.


c-Kit-dependent growth of uveal melanoma cells: a potential therapeutic target?

Abstract:
PURPOSE This study was conducted to investigate the expression and functional impact of the proto-oncogene c-kit in uveal melanoma.
METHODS Based on immunohistochemical (IHC) study of paraffin-embedded specimens from 134 uveal melanomas and Western blot analysis on eight fresh-frozen samples the expression of c-kit in uveal melanoma was studied. Furthermore, the phosphorylation of c-kit and the impact of the tyrosine kinase inhibitor STI571 was examined in the three uveal melanoma cell lines OCM-1, OCM-3, and 92-1.
RESULTS Eighty-four of 134 paraffin-embedded samples and six of eight fresh-frozen samples expressed c-kit. c-Kit was strongly expressed and tyrosine phosphorylated in cultured uveal melanoma cells compared with cutaneous melanoma cells. Moreover, in contrast to cutaneous melanoma cell lines c-kit maintained a high phosphorylation level in serum-depleted uveal melanoma cells. No activation-related mutations in exon 11 of the KIT gene were found. On the contrary, expression of the stem cell growth factor (c-kit ligand) was detected in all three uveal melanoma cell lines, suggesting the presence of autocrine (paracrine) stimulation pathways. Treatment of uveal melanoma cell lines with STI571, which blocks c-kit autophosphorylation, resulted in cell death. The IC(50) of the inhibitory effects on c-kit phosphorylation and cell proliferation was of equal size and less than 2.5 microM.
CONCLUSION The results confirm that c-kit is vastly expressed in uveal melanoma, suggest that the c-kit molecular pathway may be important in uveal melanoma growth, and point to its use as a target for therapy with STI571.


Is anorectal endosonography valuable in dyschesia?

Abstract:
AIMS Dyschesia can be provoked by inappropriate defecation movements. The aim of this prospective study was to demonstrate dysfunction of the anal sphincter and/or the musculus (m.) puborectalis in patients with dyschesia using anorectal endosonography.
METHODS Twenty consecutive patients with a medical history of dyschesia and a control group of 20 healthy subjects underwent linear anorectal endosonography (Toshiba models IUV 5060 and PVL-625 RT). In both groups, the dimensions of the anal sphincter and the m. puborectalis were measured at rest, and during voluntary squeezing and straining. Statistical analysis was performed within and between the two groups.
RESULTS The anal sphincter became paradoxically shorter and/or thicker during straining (versus the resting state) in 85% of patients but in only 35% of control subjects. Changes in sphincter length were statistically significantly different (p<0.01, chi(2) test) in patients compared with control subjects. The m. puborectalis became paradoxically shorter and/or thicker during straining in 80% of patients but in only 30% of controls. Both the changes in length and thickness of the m. puborectalis were significantly different (p<0.01, chi(2) test) in patients versus control subjects.
CONCLUSION Linear anorectal endosonography demonstrated incomplete or even absent relaxation of the anal sphincter and the m. puborectalis during a defecation movement in the majority of our patients with dyschesia. This study highlights the value of this elegant ultrasonographic technique in the diagnosis of "pelvic floor dyssynergia" or "anismus".


Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis?

Abstract:
OBJECTIVE Obesity is associated with an increased risk for cardiovascular disease. Although it is known that white adipose tissue (WAT) produces numerous proinflammatory and proatherogenic cytokines and chemokines, it is unclear whether adipose-derived chemotactic signals affect the chronic inflammation in atherosclerosis.
METHODS AND RESULTS Histological examination showed that perivascular WAT (pWAT) is in close proximity to vascular walls, particularly at sites that have a tendency to develop atherosclerosis. In rodents, the amount of pWAT is markedly increased by a high-fat diet. At a functional level, supernatant from subcutaneous and pWAT strongly induced the chemotaxis of peripheral blood leukocytes. The migration of granulocytes and monocytes was mostly mediated by interleukin-8 and monocyte chemoattractant protein-1, respectively, whereas both chemokines contributed to the migration of activated T cells. Moreover, pWAT produces these chemokines, as shown by immunohistochemistry and by explant culture. The accumulation of macrophages and T cells at the interface between pWAT and the adventitia of human atherosclerotic aortas may reflect this prochemotactic activity of pWAT.
CONCLUSION Human pWAT has chemotactic properties through the secretion of different chemokines, and we propose that pWAT might contribute to the progression of obesity-associated atherosclerosis.


Household and food shopping environments: do they play a role in socioeconomic inequalities in fruit and vegetable consumption?

Abstract:
BACKGROUND Fruit and vegetables are protective of a number of chronic diseases; however, their intakes have been shown to vary by socioeconomic position (SEP). Household and food shopping environmental factors are thought to contribute to these differences. To determine whether household and food shopping environmental factors are associated with fruit and vegetable (FV) intakes, and contribute to socioeconomic inequalities in FV consumption.
METHODS Cross-sectional data were obtained by a postal questionnaire among 4333 adults (23-85 years) living in 168 neighbourhoods in the south-eastern Netherlands. Participants agreed/disagreed with a number of statements about the characteristics of their household and food shopping environments, including access, prices and quality. Education was used to characterise socioeconomic position (SEP). Main outcome measures were whether or not participants consumed fruit or vegetables on a daily basis. Multilevel logistic regression models examined between-area variance in FV consumption and associations between characteristics of the household and food shopping environments and FV consumption.
RESULTS Only a few household and food shopping environmental factors were significantly associated with fruit and vegetable consumption, and their prevalence was low. Participants who perceived FV to be expensive were more likely to consume them. There were significant socioeconomic inequalities in fruit and vegetable consumption (ORs of not consuming fruit and vegetables were 4.26 and 5.47 among the lowest-educated groups for fruit and vegetables, respectively); however, these were not explained by any household or food shopping environmental factors.
CONCLUSION Improving access to FV in the household and food shopping environments will only make a small contribution to improving population consumption levels, and may only have a limited effect in reducing socioeconomic inequalities in their consumption.


Does birth center care during a woman's first pregnancy have any impact on her future reproduction?

Abstract:
BACKGROUND Women's experiences of childbirth may affect their future reproduction, and the model of care affects their experiences, suggesting that a causal link may exist between model of care and future reproduction. The study objective was to examine whether the birth center model of care during a woman's first pregnancy affects whether or not she has a second baby, and on the spacing to the next birth.
METHODS Between October 1989 and July 1993, a total of 1860 women at low medical risk in early pregnancy, who participated in a randomized controlled trial of in-hospital birth center care versus standard care, gave birth. The 1063 primiparas in the trial, 543 in the birth center group and 520 in the standard care group, were included in a secondary analysis in which women's personal identification codes were linked to the Swedish National Birth Register, which included information about their subsequent birth during the following 7 to 10 years. Time to an event curves were constructed by means of the Kaplan Meier method.
RESULTS The observation period after the first birth was on average 8.8 years in the birth center group and 8.7 years in the standard care group. No statistical difference was found between the groups in time to second birth, which was 2.85 and 2.82 years, respectively (median; log-rank 1.26; p=0.26).
CONCLUSION A woman's model of care, such as birth center care, during her first pregnancy does not seem to be a sufficiently important factor to affect subsequent reproduction in Sweden.


Are environmental factors important in primary systemic vasculitis?

Abstract:
OBJECTIVE To investigate the association between primary systemic vasculitis (PSV) and environmental risk factors.
METHODS Seventy-five PSV cases and 273 controls (220 nonvasculitis, 19 secondary vasculitis, and 34 asthma controls) were interviewed using a structured questionnaire. Factors investigated were social class, occupational and residential history, smoking, pets, allergies, vaccinations, medications, hepatitis, tuberculosis, and farm exposure in the year before symptom onset (index year). The Standard Occupational Classification 2000 and job-exposure matrices were used to assess occupational silica, solvent, and metal exposure. Stepwise multiple logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) adjusted for potential confounders. Total PSV, subgroups (47 Wegener's granulomatosis [WG], 12 microscopic polyangiitis, 16 Churg-Strauss syndrome [CSS]), and antineutrophil cytoplasmic antibody (ANCA)-positive cases were compared with control groups.
RESULTS Farming in the index year was significantly associated with PSV (OR 2.3 [95% CI 1.2-4.6]), with WG (2.7 [1.2-5.8]), with MPA (6.3 [1.9-21.6]), and with perinuclear ANCA (pANCA) (4.3 [1.5-12.7]). Farming during working lifetime was associated with PSV (2.2 [1.2-3.8]) and with WG (2.7 [1.3-5.7]). Significant associations were found for high occupational silica exposure in the index year (with PSV 3.0 [1.0-8.4], with CSS 5.6 [1.3-23.5], and with ANCA 4.9 [1.3-18.6]), high occupational solvent exposure in the index year (with PSV 3.4 [0.9-12.5], with WG 4.8 [1.2-19.8], and with classic ANCA [cANCA] 3.9 [1.6-9.5]), high occupational solvent exposure during working lifetime (with PSV 2.7 [1.1-6.6], with WG 3.4 [1.3-8.9], and with cANCA 3.3 [1.0-10.8]), drug allergy (with PSV 3.6 [1.8-7.0], with WG 4.0 [1.8-8.7], and with cANCA 4.7 [1.9-11.7]), and allergy overall (with PSV 2.2 [1.2-3.9], with WG 2.7 [1.4-5.7]). No other significant associations were found.
CONCLUSION A significant association between farming and PSV has been identified for the first time. Results also support previously reported associations with silica, solvents, and allergy.


Is low serum chloride level a risk factor for cardiovascular mortality?

Abstract:
BACKGROUND Serum chloride level is routinely assayed in clinical laboratories in the management of patients with kidney disorders and with metabolic diseases. It is a biological parameter that is easily, precisely and relatively cheaply measured. The epidemiological features of serum chloride levels have not been studied before.
METHODS For the random sample of men and women from the Belgian Interuniversity Research on Nutrition and Health aged 25-74 years, free of symptomatic coronary heart disease at baseline, serum chloride concentrations were measured, among those of other electrolytes. The cohort was followed up for 10 years with respect to subsequent cause-specific mortality.
RESULTS The results are based on observations of 4793 men and 4313 women. According to Cox regression analysis serum chloride level was one of the strongest predictors of total, cardiovascular disease (CVD) and non-CVD mortalities independently of age, body mass index, sex, smoking, systolic blood pressure, levels of total and high-density lipoprotein cholesterol, uric acid, serum creatinine and serum total proteins and intake of diuretics. This relation was proved to be independent of levels of other serum electrolytes and similar for men and women. The estimated adjusted risk ratio for CVD death for subjects with a serum chloride level<or =100 mmol/l compared with those with levels above that limit was 1.65 (95% confidence interval 1.06-2.57) for men and 2.16 (95% confidence interval 1.11-4.22) for women. The study of adjusted risk ratios for four groups of subjects defined on the basis of their baseline serum chloride levels revealed a decreasing log-linear 'dose-response' relation to total and cardiovascular mortalities.
CONCLUSION This s the first report from a population-based study to indicate that there is an association between serum chloride level and the incidence of total, CVD and non-CVD mortalities. The risk ratio for CVD mortality associated with a low serum chloride level was comparable to or higher than those observed for well-established CVD risk factors.


Is EQ-5D a valid quality of life instrument in patients with acute coronary syndrome?

Abstract:
OBJECTIVE To evaluate the construct validity of the Turkish version of the EQ-5D in patients with acute coronary syndrome.
METHODS The study was conducted as a cross-sectional study at the Trakya University Hospital between February and May 2008. All patients completed the Turkish version of the EQ-5D and MacNew heart-related quality of life scale. Construct validity of the EQ-5D was assessed according to relationships with MacNew subscales by using Spearman rank correlation and multiple linear regression analyses.
RESULTS One hundred and twenty-two patients responded to the instruments. Mean age was 62.9±9.3 years and male gender (88 or 72.1%) was dominant. Mean score of the EQ-5D index was 0.79±0.32, while the global score of MacNew was 5.01±1.16. The correlation coefficients of the EQ-5D index score with the MacNew subscales ranged from 0.557 to 0.721, with EQ-5D VAS score ranging from 0.297 to 0.484 (p<0.001 for all of them). According to the stepwise regression model MacNew global score was found to be significantly effective factor on EQ-5D index score (β =0.188; 95% CI: 0.152-0.224; p<0.001).
CONCLUSION The Turkish version of the EQ-5D-based utility score seems to be a valid instrument in the assessment of quality of life studies in patients with acute coronary syndrome.


Could Adult European Pharmacoresistant Epilepsy Patients Be Treated With Higher Doses of Zonisamide?

Abstract:
OBJECTIVE To examine the clinical effect (efficacy and tolerability) of high doses of zonisamide (ZNS) (>500 mg/d) in adult patients with pharmacoresistant epilepsy.
METHODS Between 2006 and 2013, all epileptic outpatients treated with high doses of ZNS were selected. Safety and efficacy were assessed based on patient and caregiver reports. Serum levels of ZNS and other concomitant antiepileptic drugs were evaluated if available.
RESULTS Nine patients (5 female): 8 focal/1 generalized pharmacoresistant epilepsy. Mean age: 34 years. Most frequent seizure type: complex partial seizures; other seizure types: generalized tonic-clonic, tonic, myoclonia. Zonisamide in polytherapy in all (100%), administered in tritherapy in 3 (33%) of 9 patients; mean dose: 633 (600-700) mg/d; efficacy (>50% seizure reduction) was observed in 5 (55%) of 9 patients. Five of 9 patients are still taking high doses of ZNS (more than 1 year). Adverse events were observed in 3 (37%) of 8 patients. Good tolerance to high doses of other antiepileptic drugs had been observed in 6 (66%) of 9 patients. Plasma levels of ZNS were only available in 2 patients; both were in the therapeutic range (34.95, 30.91) (10-40 mg/L).
CONCLUSION High doses of ZNS are effective and safe in pharmacoresistant epileptic patients. Therapeutic drug monitoring of ZNS may be considered at therapeutic failure.


Does early migraine treatment shorten time to headache peak and reduce its severity?

Abstract:
OBJECTIVE To explore whether early treatment would shorten the duration of headache from headache onset to its peak and reduce headache severity at peak.
BACKGROUND Prior clinical studies almost exclusively focused on headache relief after dosing. No data are available on whether early intervention affects the duration from headache onset to peak and headache severity at peak.
METHODS Adult migraineurs were enrolled in this observational study from multi-site headache clinics. Patients recorded their migraine experiences via an electronic diary over 1 month. Patients reported the time and pain severity at onset, dosing, and peak. We used a linear mixed model to evaluate the impact of the timing of treatment and to adjust for covariates and correlation of observations within subjects.
RESULTS A total of 182 patients reported 970 migraine episodes, 620 of which were treated before headaches progressed to peak. Mean time from headache onset to peak varied from 1.9 hours to 8.9 hours for patients treated within 15 minutes of onset and those who waited for 4 or more hours, respectively. However, early intervention was not associated with reduced headache severity at peak. In multivariate analysis, early treatment, use of triptans, and mild migraine headache in the past 3 months were significantly associated with shorter time from onset to headache peak. A separate model indicated that the timing of medication was not associated with the duration between dosing and headache peak, but use of triptans shortened the time from dosing to headache peak.
CONCLUSION Early treatment and use of triptans may lead to shorter duration from migraine headache onset to its peak but did not alleviate headache severity at peak. This could result in decreased migraine burden by reducing total migraine headache duration.


Post-tonsillectomy late haemorrhage: is it a preferably night-time event?

Abstract:
STUDY DESIGN AND SETTING This retrospective study was carried out in the Ear Nose Throat (ENT) Unit of Giannina Gaslini Institute, Genoa, Italy on children operated for adenotonsillectomy (AT) or tonsillectomy (T) between January 2003 and February 2008. We considered in the study all the post-tonsillectomy late haemorrhages irrespective of their severity and for each case we evaluated whether they recurred in the day-time (B) (between 9.00 a.m. and 9.00 p.m.) or in the night-time (A) (between 9.00 p.m. and 9.00 a.m.). Finally we considered the number of haemorrhages per hour in the whole day.
RESULTS Out of 3306 patients undergoing elective adenotonsillectomy or tonsillectomy, post-operative late haemorrhage occurred in 59 (1.78%). We noted that 42 episodes (71.2%) occurred in the night-time and 17 (28.8%) in the day-time. The average time from the operation was 8.4 days. A statistically significant difference (p=0.002) was found when comparing the frequencies of night-time and day-time haemorrhages. We did not observe any significant difference in the distribution per hour of the haemorrhages.
CONCLUSION The incidence of post-tonsillectomy late haemorrhage in our study population was 1.78%. A statistically significant difference was found between night-time and day-time haemorrhages. Even though no significant distribution of haemorrhages per hour was observed, we underline that we recorded 32 (54.2%) events in 2 periods of the day: from 10 p.m. to 1 a.m. and from 6 to 9 a.m.


Acute hepatitis C in Israel: a predominantly iatrogenic disease?

Abstract:
BACKGROUND AND AIMS Acute hepatitis C virus infection in the era of universal screening of blood products has not disappeared, and is thought to be transmitted primarily via injecting drug use. A growing body of evidence supports iatrogenic transmission as an important mode of transmission. The aim of this study was to examine transmission routes and clinical characteristics in a group of patients with acute hepatitis C in Israel.
METHODS A retrospective chart review was conducted in three different liver clinics in Israel, of all new hepatitis C patients. Patients identified as possible acute hepatitis C were re-interviewed and all other sources such as blood bank records and pre-employment check-ups reviewed in order to establish the diagnosis of acute hepatitis C infection and to identify the transmission route.
RESULTS Twenty-nine patients were found to have acute hepatitis C, representing 0.75% of all new referrals for hepatitis C. The most frequent (65%) mode of transmission was iatrogenic involving several, often minimal, procedures and clinical settings. The group in which iatrogenic transmission was suspected was older and the patients more often in monogamous relationship compared with other transmission routes groups. Injecting drug use was the second most common route of infection. Spontaneous seroconversion has occurred in approximately one third of the patients.
CONCLUSION Acute hepatitis C in the post universal blood products screening era was found to be predominantly an iatrogenic disease in the investigated localities. This finding should direct attention and resources towards the development and implementation of preventive measures.


Do adjuvant aromatase inhibitors increase the cardiovascular risk in postmenopausal women with early breast cancer?

Abstract:
BACKGROUND Despite the advantages from using aromatase inhibitors (AIs) compared with tamoxifen for early breast cancer, an unexpectedly greater number of grade 3 and 4 cardiovascular events (CVAE) (as defined by National Cancer Institute of Canada-Common Toxicity Criteria [version 2.0] was demonstrated.
METHODS Phase 3 randomized clinical trials (RCTs) comparing AI with tamoxifen in early breast cancer were considered eligible for this review. The event-based risk ratios (RRs) with 95% confidence intervals (95% CIs) were derived, and a test of heterogeneity was applied. Finally, absolute differences (ADs) in event rates and the number of patients needed to harm 1 patient (NNH) were determined.
RESULTS Seven eligible RCTs (19,818 patients) reported CVAE results. When considering all RCTs, the AD of the primary endpoint (CVAE) between the 2 arms (0.52%), tamoxifen versus AI, was statistically significant (RR, 1.31; 95% CI, 1.07-1.60; P= .007). This translated into an NNH value of 189 patients; when only third-generation AIs were considered, the difference (0.57%) remained significant (RR, 1.34; 95% CI, 1.09-1.63; P= .0038). Thromboembolic events were significantly more frequent in the tamoxifen arm, regardless of the strategy adopted (RR, 0.53; 95% CI, 0.42-0.65; P<.0001), without significant heterogeneity (P= .21). An AD of 1.17% and an NNH value of 85 patients were observed.
CONCLUSION According to the results from this meta-analysis, the risk of grade 3 and 4 CVAEs in patients who were receiving AIs was higher compared with the risk in patients who were receiving tamoxifen, and the difference reached statistical significance. However, the AD was relatively low, and from 160 to 180 patients had to be treated to produce 1 event.


Metastatic carcinoma to the cervical nodes from an unknown head and neck primary site: Is there a need for neck dissection?

Abstract:
BACKGROUND The aim of the study was to evaluate the outcomes and patterns of failure in patients with metastatic carcinoma to cervical lymph nodes from an unknown head and neck primary origin, who were treated curatively with radiotherapy, with or without neck dissection.
METHODS The study included 61 patients referred to the McGill University Hospital Centers from 1987 to 2002. The median age was 57 years, with male to female ratio of 4:1. Distribution of patients by N status was as follows: N1, 16 patients (26%); N2a, 18 (30%); N2b, 13 (22%); N2c, 7 (11%); and N3, 7 (11%). Twenty patients underwent neck dissection (11 radical, 9 functional) and 41 patients had biopsy (9 fine-needle aspiration and 32 excisional biopsy). All patients received radiotherapy. The median dose to the involved node(s) was 64 Gy, and 60 Gy to the rest of the neck. Treatment of the neck was bilateral in 50 patients (82%) and ipsilateral in 11 (18%). The minimum duration of the follow-up was 12 months, with the median of 32 months.
RESULTS The 5- and 8-year overall survival for the whole population was 79% and 67%, respectively. There was no statistically significant difference in the 8-year actuarial overall survival (64.8% and 67.6%, respectively, p = .64) and local relapse-free survival (75% vs 74.5%, respectively, p = .57), among patients who had biopsy versus those who had neck dissection.
CONCLUSION In our experience, definitive radiotherapy to the neck and the potential mucosal sites, whether preceded by neck dissection or not, is effective to achieve a good local control rate in the unknown primary cancer of the head and neck. The indication for neck dissection, in particular for early nodal stage, is controversial.


Cardiac reoperations in octogenarians: Do they really benefit?

Abstract:
METHODS We retrospectively identified 84 consecutive patients aged ≥80 years, who underwent a cardiac reoperation at the department for Cardiothoracic Surgery in the Heart&Vessel Center Bad Bevensen between January 2007 and 2013. Demographic profiles as well as operative data were analyzed, and the patients were prospectively followed. Patient's functional status and quality of life were assessed with the Barthel Index, New York Heart Association class and the short form-12 questionnaire.
RESULTS The mean age of the study group (61 men, 23 women) was 81.9 ± 1.9 years. Most redo-procedures were carried out after primary coronary artery bypass grafting (65%), primary aortic valve replacement (21%) and primary mitral valve replacement (6%). The most frequent actual surgical procedures were combined coronary artery bypass grafting and aortic valve replacement (26%), isolated coronary artery bypass grafting (19%), and isolated aortic valve replacement (19%). The mean length of hospital stay was 17 ± 15 days. In-hospital mortality counted for 32.1%. During follow up (29 ± 20 months) a further 19.0% of the patients died. The Barthel Index of the survivors was 89 ± 17 and their mean New York Heart Association class was 2 ± 1. A total of 93% of the patients were living at home. Summary scores of physical and mental health of the short form-12 questionnaire equalled those of an age- and sex-matched normative population.
CONCLUSION Despite high perioperative mortality, results document a sustainable recovery of the survivors offering the prospect of a highly independent and satisfying life. Therefore, advanced age alone should not be a contraindication for redo cardiac interventions. Geriatr Gerontol Int 2016; 16: 1138-1144.


Is Alveolar Macrophage Phagocytic Dysfunction in Children With Protracted Bacterial Bronchitis a Forerunner to Bronchiectasis?

Abstract:
BACKGROUND Children with recurrent protracted bacterial bronchitis (PBB) and bronchiectasis share common features, and PBB is likely a forerunner to bronchiectasis. Both diseases are associated with neutrophilic inflammation and frequent isolation of potentially pathogenic microorganisms, including nontypeable Haemophilus influenzae (NTHi), from the lower airway. Defective alveolar macrophage phagocytosis of apoptotic bronchial epithelial cells (efferocytosis), as found in other chronic lung diseases, may also contribute to tissue damage and neutrophil persistence. Thus, in children with bronchiectasis or PBB and in control subjects, we quantified the phagocytosis of airway apoptotic cells and NTHi by alveolar macrophages and related the phagocytic capacity to clinical and airway inflammation.
METHODS Children with bronchiectasis (n = 55) or PBB (n = 13) and control subjects (n = 13) were recruited. Alveolar macrophage phagocytosis, efferocytosis, and expression of phagocytic scavenger receptors were assessed by flow cytometry. Bronchoalveolar lavage fluid interleukin (IL) 1β was measured by enzyme-linked immunosorbent assay.
RESULTS For children with PBB or bronchiectasis, macrophage phagocytic capacity was significantly lower than for control subjects (P = .003 and P<.001 for efferocytosis and P = .041 and P = .004 for phagocytosis of NTHi; PBB and bronchiectasis, respectively); median phagocytosis of NTHi for the groups was as follows: bronchiectasis, 13.7% (interquartile range [IQR], 11%-16%); PBB, 16% (IQR, 11%-16%); control subjects, 19.0% (IQR, 13%-21%); and median efferocytosis for the groups was as follows: bronchiectasis, 14.1% (IQR, 10%-16%); PBB, 16.2% (IQR, 14%-17%); control subjects, 18.1% (IQR, 16%-21%). Mannose receptor expression was significantly reduced in the bronchiectasis group (P = .019), and IL-1β increased in both bronchiectasis and PBB groups vs control subjects.
CONCLUSION A reduced alveolar macrophage phagocytic host response to apoptotic cells or NTHi may contribute to neutrophilic inflammation and NTHi colonization in both PBB and bronchiectasis. Whether this mechanism also contributes to the progression of PBB to bronchiectasis remains unknown.


Is minilaparoscopic inguinal hernia repair feasible?

Abstract:
INTRODUCTION Laparoscopy has rapidly emerged as the preferred surgical approach to a number of different diseases because it allows for a correct diagnosis and proper treatment. It seems to be moving toward the use of mini-instruments (5 mm or less in diameter). The aim of this paper is to illustrate retrospectively the results of an initial experience of minilaparoscopic transabdominal preperitoneal (miniTAPP) repair of groin hernia defects performed at two institutions.
MATERIALS AND METHODS Between February 2000 and December 2003, a total of 303 patients (mean age, 45 years) underwent a miniTAPP procedure: 213 patients (70.2%) were operated on bilaterally and 90 (28.7%) for a unilateral defect, with a total of 516 hernia defects repaired. The primary endpoint was the feasibility rate for miniTAPP. The secondary endpoint was the incidence of mini-TAPP-related complications.
RESULTS No conversions to laparoscopy or an anterior open approach were required. There were no major complications, while minor complications ranged as high as 0.3%.
CONCLUSION While limited by its retrospective design, the present study indicates that the minilaparoscopic approach to groin hernia repair is safe and effective, making miniTAPP a challenging alternative to laparoscopy in the approach to groin hernia repair.


Surgical treatment of prosthetic valve endocarditis in patients with double prostheses: is single-valve replacement safe?

Abstract:
OBJECTIVE Bias against operating on patients with prosthetic valve endocarditis (PVE) who have multiple prostheses may preclude the use of life-saving valve replacement. We investigated the accuracy of the preoperative diagnosis of PVE in patients with both mitral and aortic prosthesis and the safety of single-valve replacement when only one valve seemed infected.
METHODS Patients with a diagnosis of active PVE who had mitral and aortic prosthesis in place were assessed. We looked at the methods for diagnosis, causative agents, indication for valve replacement, operative findings and outcome.
RESULTS Twenty patients, who had both mitral and aortic prostheses and a diagnosis of PVE, were assessed. Streptococci and staphylococci caused 70% of cases. By means of echocardiography, the valves involved were: mitral (11 patients), aortic (six patients), and in three cases both prosthetic valves seemed infected. Surgery was undertaken in 17 patients (85%). The positive predictive value of transesophageal echocardiogram (TEE) for the preoperative diagnosis of the site of infection was 100%. In 13 patients, only the prosthetic valve that seemed infected was replaced. Four of these patients died within a week after the procedure. Nine patients survived the surgical procedure, completed a course of antimicrobial therapy and were followed up for 15.78 months (95% CI: 12.83-18.72). All were considered cured and relapses were not observed.
CONCLUSION TEE allowed a diagnosis of site involvement that did correlate with the anatomic diagnosis obtained during the operation. This fact contributed to the management of patients and was of great help in guiding the surgical intervention. Echo-oriented single-valve replacement may be a safe strategy for patients with PVE and double prostheses.


Epidural analgesia for surgical treatment of peritoneal carcinomatosis: a risky technique?

Abstract:
BACKGROUND To study the risks of haemodynamic instability, and the possible occurrence of spinal haematoma, meningitis and epidural abscess when epidural analgesia is performed for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).
METHODS We retrospectively analyzed the data of 35 patients treated by HIPEC with oxaliplatin or cisplatin. An epidural catheter was inserted before induction of general anaesthesia. Postoperatively, a continuous epidural infusion of ropivacain, then a patient-controlled epidural analgesia were started.
RESULTS The epidural catheter was used peroperatively before HIPEC in 12 subjects (34%), and after HIPEC in 23 subjects (66%). The median dose of ropivacain given peroperatively in the epidural catheter was 40 mg (30-75). Norepinephrin was used in two subjects (6%) peroperatively (median infusion rate 0.325 μg/kg per minute [0.32-0.33]), and in four subjects (11%) in the postoperative 24 hours. No spinal haematoma, meningitis or epidural abscess were noted. Five subjects (14%) had a thrombopenia or a prothrombin time less than 60% before catheter removal. Two subjects (6%) had a leukopenia before catheter removal. No thrombopenia or blood coagulation disorders were recorded the day of catheter removal.
CONCLUSION In this series of 35 patients, the use of epidural analgesia for HIPEC does not seem to be associated with a worse risk of haemodynamic instability, spinal haematoma, meningitis or epidural abscess. HIPEC with platinum salt is not incompatible with the safety of epidural analgesia, with an optimized fluid management peroperatively and the following of perimedullary anesthesia practice guidelines.


Risk stratification in emergency surgical patients: is the APACHE II score a reliable marker of physiological impairment?

Abstract:
HYPOTHESES The APACHE II (Acute Physiology and Chronic Health Evaluation II) score used as an intensive care unit (ICU) admission score in emergency surgical patients is not independent of the effects of treatment and might lead to considerable bias in the comparability of defined groups of patients and in the evaluation of treatment policies. Postoperative monitoring with the APACHE II score is clinically irrelevant.
DESIGN Inception cohort study.
SETTING Secondary referral center.
PATIENTS Eighty-five consecutive emergency surgical patients admitted to the surgical ICU in 1999. The APACHE II score was calculated before surgery; after admission to the ICU; and on postoperative days 3, 7, and 10.
MAIN OUTCOME MEASURES APACHE II scores and predicted and observed mortality rates.
RESULTS The mean +/- SD APACHE II score of 24.2 +/- 8.3 at admission to the ICU was approximately 36% greater than the initial APACHE II score of 17.8 +/- 7.7, a difference that was highly statistically significant (P<.001). The overall mortality of 32% favorably corresponds with the predicted mortality of 34% according to the initial APACHE II score. However, the predicted mortality of 50% according to the APACHE II score at admission to the ICU was significantly different from the observed mortality rate (P =.02). In 40 long-term patients (>/=10 days in the ICU), the difference between the APACHE II scores of survivors and patients who died was statistically significant on day 10 (P =.04).
CONCLUSION For risk stratification in emergency surgical patients, it is essential to measure the APACHE II score before surgical treatment. Longitudinal APACHE II scoring reveals continuous improvement of the score in surviving patients but has no therapeutic relevance in the individual patient.


Are physicians meeting the needs of family caregivers of the frail elderly?

Abstract:
OBJECTIVE To explore expressed needs, both formal and informal, of family caregivers of frail elderly. To evaluate roles of physicians.
DESIGN Questionnaire survey of members of the Montreal Jewish community providing care for frail elderly family members.
SETTING Jewish community of Montreal.
PARTICIPANTS Volunteer caregivers who were caring for a family member or friend 60 years or older, who had greatest responsibility for providing physical or emotional support to an elderly person, who saw themselves as caregivers, and who could speak English or French were studied. Of 118 volunteers, 32 were excluded because they withdrew for personal reasons or because they did not meet study criteria.
MAIN OUTCOME MEASURES Demographic variables, functional status of the care receiver, use of home care services, and needs assessment to identify additional services.
RESULTS An average of 75.4% respondents did not use formal support services. Just under half of caregivers were dissatisfied with the attention they received from the health care system, and more than one third expressed feelings of stress, depression, guilt, and isolation.
CONCLUSION Hypotheses for this discontent are presented. Physicians may be uninterested in helping caregivers; even if they were receptive to counseling caregivers, they could be poorly remunerated for the types of counseling sessions that are usual for caregivers; and being a professional caregiver to family caregivers is demanding in itself.


Are Reviewers' Scores Influenced by Citations to Their Own Work?

Abstract:
STUDY OBJECTIVE Academic medical researchers are judged by how often their publications are cited in the literature. When serving as journal reviewers, they may be more favorably disposed to manuscripts that cite their work. We investigate whether manuscripts that contain a citation to the reviewer's work receive higher evaluations than those that do not and whether peer reviewers encourage authors to cite that reviewer's work.
METHODS We analyzed all research manuscripts submitted in 2012 to Annals of Emergency Medicine to determine whether they contained citations to each reviewer's work. To determine whether citation affected reviewer scores, we obtained each reviewer's score of the manuscript's overall desirability (1=worst to 5=best) and used descriptive statistics and regression modeling to compare scores of cited and noncited reviewers. We also enumerated how often reviewers suggested that authors add citations to the reviewer's work or other work.
RESULTS There were 395 manuscripts and 999 corresponding reviews with an manuscript desirability score. The 83 reviews by cited reviewers (8.3%) had a mean score of 2.8 (SD 1.4); the 916 reviews by noncited reviewers (91.7%), 2.5 (1.2; Δ=0.3; 95% confidence interval [CI] 0 to 0.6). The mean score in the 117 reviews of the noncited reviewers of the 57 manuscripts that had both cited and noncited reviewers was 2.9 (SD 1.2) compared with 2.9 (SD 1.1) for the 68 reviews by cited reviewers (Δ=0; 95% CI -0.3 to 0.4). In the final ordinal regression model, the unadjusted OR for the manuscript desirability score was 1.6 (95% CI 1.0 to 2.7); when adjusting for the manuscripts' mean desirability score, it was 1.4 (95% CI 0.8 to 2.2), demonstrating that manuscript quality was a confounder. Authors were asked to add a citation to the reviewer's work in 28 reviews (3%) but to others' work in 98 (10%).
CONCLUSION In a leading specialty journal, cited reviewers gave higher scores than noncited reviewers. However, this was likely due to their being assigned higher-quality manuscripts and not because they were cited in the manuscript. Reviewer requests that their work be cited were rare.


Does the central venous pressure predict fluid responsiveness?

Abstract:
BACKGROUND Despite a previous meta-analysis that concluded that central venous pressure should not be used to make clinical decisions regarding fluid management, central venous pressure continues to be recommended for this purpose.AIM: To perform an updated meta-analysis incorporating recent studies that investigated indices predictive of fluid responsiveness. A priori subgroup analysis was planned according to the location where the study was performed (ICU or operating room).
DATA SOURCES MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles.
STUDY SELECTION Clinical trials that reported the correlation coefficient or area under the receiver operating characteristic curve (AUC) between the central venous pressure and change in cardiac performance following an intervention that altered cardiac preload. From 191 articles screened, 43 studies met our inclusion criteria and were included for data extraction. The studies included human adult subjects, and included healthy controls (n = 1) and ICU (n = 22) and operating room (n = 20) patients.
DATA EXTRACTION Data were abstracted on study characteristics, patient population, baseline central venous pressure, the correlation coefficient, and/or the AUC between central venous pressure and change in stroke volume index/cardiac index and the percentage of fluid responders. Meta-analytic techniques were used to summarize the data.
DATA SYNTHESIS Overall 57% ± 13% of patients were fluid responders. The summary AUC was 0.56 (95% CI, 0.54-0.58) with no heterogenicity between studies. The summary AUC was 0.56 (95% CI, 0.52-0.60) for those studies done in the ICU and 0.56 (95% CI, 0.54-0.58) for those done in the operating room. The summary correlation coefficient between the baseline central venous pressure and change in stroke volume index/cardiac index was 0.18 (95% CI, 0.1-0.25), being 0.28 (95% CI, 0.16-0.40) in the ICU patients, and 0.11 (95% CI, 0.02-0.21) in the operating room patients.
CONCLUSION There are no data to support the widespread practice of using central venous pressure to guide fluid therapy. This approach to fluid resuscitation should be abandoned.


Memory-provoked rCBF-SPECT as a diagnostic tool in Alzheimer's disease?

Abstract:
PURPOSE Alzheimer's disease (AD) is a primary degenerative disease that progressively affects all brain functions, with devastating consequences for the patient, the patient's family and society. Rest regional cerebral blood flow (rCBF) could have a strategic role in differentiating between AD patients and normal controls, but its use for this purpose has a low discriminatory capacity. The purpose of this study was to evaluate whether the diagnostic sensitivity of rCBF single-photon emission computed tomography (SPECT) could be increased by using an episodic memory task provocation, i.e. memory-provoked rCBF-SPECT (MP-SPECT).
METHODS Eighteen persons (73.2+/-4.8 years) with mild AD and 18 healthy elderly (69.4+/-3.9 years) were included in the study. The subjects were injected with (99m)Tc-hexamethylpropylene amine oxime (HMPAO) during memory provocation with faces and names, followed by an rCBF-SPECT study. The rCBF (99m)Tc-HMPAO SPECT images were analysed using statistical parametric mapping (SPM2). Peaks with a false discovery rate corrected value of 0.05 were considered significant.
RESULTS On MP-SPECT, the AD group showed a significant rCBF reduction in the left parietal cortex in comparison with healthy elderly. At rest, no significant group differences were seen.
CONCLUSION Memory provocation increased the sensitivity of rCBF-SPECT for the detection of AD-related blood flow changes in the brain at the group level. Further studies are needed to evaluate MP-SPECT as a diagnostic tool at the individual level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might be sufficient in the clinical setting.


Can we ease the financial burden of colonoscopy?

Abstract:
BACKGROUND Polyps identified at colonoscopy are predominantly diminutive (<5 mm) with a small risk (>1%) of high-grade dysplasia or carcinoma; however, the cost of histological assessment is substantial.AIM: The aim of this study was to determine whether prediction of colonoscopy surveillance intervals based on real-time endoscopic assessment of polyp histology is accurate and cost effective.
METHODS A prospective cohort study was conducted across a tertiary care and private community hospital. Ninety-four patients underwent colonoscopy and polypectomy of diminutive (≤5 mm) polyps from October 2012 to July 2013, yielding a total of 159 polyps. Polyps were examined and classified according to the Sano-Emura classification system. The endoscopic assessment (optical diagnosis) of polyp histology was used to predict appropriate colonoscopy surveillance intervals. The main outcome measure was the accuracy of optical diagnosis of diminutive colonic polyps against the gold standard of histological assessment.
RESULTS Optical diagnosis was correct in 105/108 (97.2%) adenomas. This yielded a sensitivity, specificity and positive and negative predictive values (with 95%CI) of 97.2% (92.1-99.4%), 78.4% (64.7-88.7%), 90.5% (83.7-95.2%) and 93% (80.9-98.5%) respectively. Ninety-two (98%) patients were correctly triaged to their repeat surveillance colonoscopy. Based on these findings, a cut and discard approach would have resulted in a saving of $319.77 per patient.
CONCLUSION Endoscopists within a tertiary care setting can accurately predict diminutive polyp histology and confer an appropriate surveillance interval with an associated financial benefit to the healthcare system. However, limitations to its application in the community setting exist, which may improve with further training and high-definition colonoscopes.


Is external palliative radiotherapy for gallbladder carcinoma effective?

Abstract:
BACKGROUND Gallbladder carcinoma is characterized by delayed diagnosis, ineffective treatment and poor prognosis. Surgical resection has been thought to be the treatment of choice, while the role of radiotherapy as adjuvant or palliative treatment has not been fully clarified in the literature.
PATIENT AND METHODS We present the case of a 45-year-old female, with unresectable gallbladder carcinoma, grade IV, histologically diagnosed during laparotomy. The patient was treated with palliative intent with percutaneous transhepatic biliary drainage. Furthermore, she received external radiotherapy by (60)Co, using a three-field technique (anterior-posterior and right lateral). The total dose was 3,000 cGy in 10 fractions, with 300 cGy per fraction, 5 days weekly.
RESULTS The patient showed clinico-laboratory improvement and was discharged with a permanent percutaneous transhepatic endoprosthesis. During follow-up (10 and 12 months postirradiation), abdominal CTs showed no local extension of the tumor, while the patient had a good performance status. So far, 1 year after the diagnosis of gallbladder cancer she is still alive.
CONCLUSION External radiotherapy seems to be a safe and effective method of palliative management of gallbladder carcinoma. However, further studies are necessary to determine the role of radiotherapy in palliative or adjuvant treatment of gallbladder carcinoma.


Chemical shift MRI: is there any contribution to morphologic evaluation of solid breast masses?

Abstract:
RATIONALE AND OBJECTIVES To investigate the contribution of chemical shift magnetic resonance imaging for assessment of the margins of solid breast masses by benefiting from India ink artifact.
METHODS AND MATERIALS Eighty-eight masses in 64 patients were evaluated in T1- and T2-weighted images, dynamic contrast and chemical shift studies according to Breast Imaging Reporting and Data System magnetic resonance lexicon. Subtraction images were automatically obtained by chemical shift imaging and dynamic studies. Each sequence was scored using a scale of 1 to 5 according to its ability to demonstrate margins separate from surrounding parenchyma. Breast parenchyma was evaluated as fatty and dense. The results were compared with the histopathologic results.
RESULTS Twenty-eight (31.8%) of the lesions were localized in fatty breast, and the remaining 60 (68.2%) lesions were localized in dense breast. There were 34 (38.6%) benign and 54 (61.4%) malignant masses. In fatty breast, chemical shift subtraction and T1-weighted images were valuable both for the demonstration and differentiation of benign lesions (P<.05). None of the sequence was valuable for both the demonstration and differentiation of malignant lesions in fatty breasts (P>.05). In dense breasts, chemical shift subtraction and dynamic contrast subtraction images were valuable for both the demonstration and differentiation of benign and malignant lesions. Additional to these sequences, T2-weighted images was also valuable for benign lesions (P<.05).
CONCLUSION Chemical shift subtraction can contribute to routine dynamic contrast subtraction in morphologic analysis particularly for the evaluation of margins of benign lesions in fatty breasts. It can also help in morphologic analysis of masses in dense breast.


Do some U.S. states have higher/lower injury mortality rates than others?

Abstract:
BACKGROUND This article examines the hypothesis that the six U.S. states with the highest rates of road traffic deaths (group 1 states) also had above-average rates of other forms of injury such as falling, poisoning, drowning, fire, suffocation, homicide, and suicide, and also for the retail trade and construction industries. The converse, second hypothesis, for the six states with the lowest rates of road traffic deaths (group 2 states) is also examined.
RESULTS Data for these 12 states for the period 1983 to 1995 included nine categories of unintentional and four categories of intentional injury. Seventy-four percent of the group 1 states conformed to the first hypothesis, and 85% of the group 2 states conformed to the second hypothesis.
CONCLUSION Group 1 states are likely to exhibit above-average rates for most other categories of injury death, whereas group 2 states are even more likely to exhibit below-average rates for most other categories of injury death.


Do antibiotics decrease post-tonsillectomy morbidity?

Abstract:
OBJECTIVE A tonsillectomy audit was carried out and compared with other studies, to emphasize the role of antibiotics.
METHODS This study was carried out at North West Armed Forces Hospital, Tabuk, Kingdom of Saudi Arabia, during the year January 1999 through to December 1999. This is a retrospective study of patients who had tonsillectomy with or with adenoidectomy, the topics audited included indication for surgery, grade of surgeon, method of surgery, length of hospital stay, complications and the use of postoperative antibiotics.
RESULTS A total of 185 patients underwent tonsillectomy with or without adenoidectomy. The patients age ranged between 2 years to 53 years and the majority were children. In our audit we found no difference with regard to grade of surgeons, method of hemostasis in the outcome of surgery. Moreover, postoperative antibiotics had no role in pain control, postoperative fever, secondary hemorrhage or reduction in hospital stay. The administration of analgesics on the basis of, as required, had poor pain control.
CONCLUSION Post tonsillectomy antibiotics did not prove to have a role in minimizing postoperative morbidity. Moreover, analgesics given on the basis of as required had a limited value.


Body diffusion-weighted MR imaging of uterine endometrial cancer: is it helpful in the detection of cancer in nonenhanced MR imaging?

Abstract:
OBJECTIVE In this study, the authors discussed the feasibility and value of diffusion-weighted (DW) MR imaging in the detection of uterine endometrial cancer in addition to conventional nonenhanced MR images.
METHODS AND MATERIALS DW images of endometrial cancer in 23 patients were examined by using a 1.5-T MR scanner. This study investigated whether or not DW images offer additional incremental value to conventional nonenhanced MR imaging in comparison with histopathological results. Moreover, the apparent diffusion coefficient (ADC) values were measured in the regions of interest within the endometrial cancer and compared with those of normal endometrium and myometrium in 31 volunteers, leiomyoma in 14 patients and adenomyosis in 10 patients. The Wilcoxon rank sum test was used, with a p<0.05 considered statistically significant.
RESULTS In 19 of 23 patients, endometrial cancers were detected only on T2-weighted images. In the remaining 4 patients, of whom two had coexisting leiomyoma, no cancer was detected on T2-weighted images. This corresponds to an 83% detection sensitivity for the carcinomas. When DW images and fused DW images/T2-weighted images were used in addition to the T2-weighted images, cancers were identified in 3 of the remaining 4 patients in addition to the 19 patients (overall detection sensitivity of 96%). The mean ADC value of endometrial cancer (n=22) was (0.97+/-0.19)x10(-3)mm(2)/s, which was significantly lower than those of the normal endometrium, myometrium, leiomyoma and adenomyosis (p<0.05).
CONCLUSION DW imaging can be helpful in the detection of uterine endometrial cancer in nonenhanced MR imaging.


Do inhaled steroids differ from cromones in terms of hospital admission rates for asthma in children?

Abstract:
METHODS Annual data on children aged under 16 y treated for asthma, including consumption of regular medication for asthma, numbers of hospital periods, lengths of hospitalizations and annual proportions of readmissions, were collected using patient-specific medical records from 1995 to 1999. In the Kuopio province, on average, 35.6-36.7/1000 children were on maintenance for asthma, of which 23% were receiving cromones, 51% were taking inhaled steroids and 26% were treated with cromones plus intermittent steroids. In the Oulu province, the respective prevalence was 32.7-34.9/1000, and the respective proportions were 5%, 93% and 2%.
RESULTS Total and first admissions, as well as hospital days were clearly less in the Oulu province. In the children aged>or = 6y, the average annual total admissions were 0.3/1000 (Oulu) vs 1.2/1000 (Kuopio) (p<0.001). Similarly, the first admissions were 0.2/1000 vs 1.0/1000 (p<0.001), proportions of readmissions 6.3% vs 19.3% (p<0.05), and numbers of hospital days 0.7/1000 vs 3.8/1000 (p<0.001). The differences were in the same direction, though less prominent, also among children 2-5 y of age.
CONCLUSION Our results suggest that inhaled steroids are better than cromones in preventing admissions for asthma when two provinces with different practices for maintenance medication of steady-state asthma were compared.


Substance use and HIV-related sexual behaviors among US high school students: are they related?

Abstract:
OBJECTIVES This study was undertaken to examine whether use of alcohol, cigarettes, marijuana, cocaine, and other illicit drugs is related to the likelihood of sexual behaviors that increase risk for human immunodeficiency virus (HIV) infection among youth.
METHODS The 1990 national Youth Risk Behavior Survey was used to collect self-reported information about a broad range of health risk behaviors from a representative sample of 11,631 high school students in the United States.
RESULTS Students who reported no substance use were least likely to report having had sexual intercourse, having had four or more sex partners, and not having used a condom at last sexual intercourse. Adjusted for age, sex, and race/ethnicity, odds ratios for each of these sexual risk behaviors were greatest among students who had used marijuana, cocaine, or other illicit drugs. Students who had used only alcohol or cigarettes had smaller but still significant increases in the likelihood of having had sexual intercourse and of having had four or more sex partners.
CONCLUSION HIV prevention programs for youth should recognize that substance use may be an important indicator of risk for HIV infection and acquired immunodeficiency syndrome through its association with unsafe sexual behaviors.


Do teleoncology models of care enable safe delivery of chemotherapy in rural towns?

Abstract:
OBJECTIVES To compare the dose intensity and toxicity profiles for patients undergoing chemotherapy at the Townsville Cancer Centre (TCC), a tertiary cancer centre in northern Queensland, with those for patients treated in Mount Isa, supervised by the same medical oncologists via teleoncology.
DESIGN A quasi-experimental design comparing two patient groups.
SETTING TCC and Mount Isa Hospital, which both operate under the auspices of the Townsville Teleoncology Network (TTN).
PARTICIPANTS Eligible patients who received chemotherapy at TCC or Mt Isa Hospital between 1 May 2007 and 30 April 2012.
INTERVENTION Teleoncology model for managing cancer patients in rural towns.
MAIN OUTCOME MEASURES Dose intensity (doses, number of cycles and lines of treatment) and toxicity rates (rate of serious side effects, hospital admissions and mortality).
RESULTS Over 5 years, 89 patients received a total of 626 cycles of various chemotherapy regimens in Mount Isa. During the same period, 117 patients who received a total of 799 cycles of chemotherapy at TCC were eligible for inclusion in the comparison group. There were no significant differences between the Mount Isa and TCC patients in most demographic characteristics, mean numbers of treatment cycles, dose intensities, proportions of side effects, and hospital admissions. There were no toxicity-related deaths in either group.
CONCLUSION It appears safe to administer chemotherapy in rural towns under the supervision of medical oncologists from larger centres via teleoncology, provided that rural health care resources and governance arrangements are adequate.


Does Paget's disease exist in India?

Abstract:
OBJECTIVE Paget's disease of bone has been described as a few case reports from India. The aim of the present study is to document the existence of Paget's disease (PD) in India.
MATERIAL AND METHODS We describe demography, clinical manifestations, biochemical and radiological profile and the treatment outcome of 21 patients of PD.
RESULTS Mean (+/-SD) age of these patients at presentation was 49.2 +/- 17.6 years and the male to female ratio was 2.5:1. Common clinical manifestations included backache, headache and bone pains. Others were fracture, joint pain, deafness, gait ataxia, visual impairment and difficulty in biting. Two patients presented with hydrocephalus and one had recurrent paraparesis. Fifteen (71.4%) patients had polyostotic and six (28.6%) had monoostotic Paget's disease. More commonly involved bones were skull and spine (61.9%) followed by pelvis (38.1%), femur (33.3%), tibia (9%) and ulna (9%). Mean (+/-SD) serum alkaline phosphatase at diagnosis was 1514 +/- 1168 IU/L and nine months after treatment with bisphosphonates decreased to 454 +/- 406 IU/ L(P<0.03).
CONCLUSION This illustrates that Paget's disease does exist in India and a high index of suspicion is required to clinch the diagnosis.


Is There an Additional Value of Using Somatostatin Receptor Subtype 2a Immunohistochemistry Compared to Somatostatin Receptor Scintigraphy Uptake in Predicting Gastroenteropancreatic Neuroendocrine Tumor Response?

Abstract:
BACKGROUND AND AIMS It is unknown whether tumoral somatostatin receptor subtype 2a (sst2a) immunohistochemistry (IHC) has additional value compared to somatostatin receptor scintigraphy (SRS) uptake using OctreoScan® in predicting response to peptide receptor radiotherapy using 177Lu-octreotate (PRRT) in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The aims of this study were: (1) to establish the percentage of sst2a immunopositivity in GEP-NET samples of PRRT-treated patients, (2) to determine the relationship between best GEP-NET response using RECIST 1.0 criteria 1 year after PRRT and tumoral sst2a IHC, and (3) to compare characteristics of patients with sst2a IHC-negative and -positive tumors.
METHODS All 73 consecutive patients were selected for PRRT based on a positive SRS. Radiological response was scored according to RECIST 1.0 criteria. sst2a status was detected on tumor samples by IHC.
RESULTS In total, 93% of GEP-NET samples showed sst2a IHC positivity. No statistically significant relationship was observed between in vitro sst2a expression and in vivo best GEP-NET response 1 year after PRRT (p = 0.47). Sex, primary tumor site, disease stage, ENETS TNM classification, Ki-67 index, highest serum chromogranin-A level, and highest neuron-specific enolase level were not significantly different between patients with negative and positive sst2a tumoral IHC with the exception of age at diagnosis (p = 0.007).
CONCLUSION sst2a IHC of tumor samples has no additional value compared to SRS uptake using OctreoScan® in predicting tumor response after PRRT.


Does Molecular Genotype Provide Useful Information in the Management of Radioiodine Refractory Thyroid Cancers?

Abstract:
INTRODUCTION Whether mutation status should be used to guide therapy is an important issue in many cancers. We correlated mutation profile in radioiodine-refractory (RAIR) metastatic thyroid cancers (TCs) with patient outcome and response to tyrosine kinase inhibitors (TKIs), and discussed the results with other published data.
MATERIALS AND METHODS Outcome in 82 consecutive patients with metastatic RAIR thyroid carcinoma prospectively tested for BRAF, RAS and PI3KCA mutations was retrospectively analyzed, including 55 patients treated with multikinase inhibitors.
RESULTS Papillary thyroid carcinomas (PTCs) were the most frequent histological subtype (54.9 %), followed by poorly differentiated thyroid carcinoma [PDTC] (30.5 %) and follicular thyroid carcinoma [FTC](14.6 %). A genetic mutation was identified in 23 patients (28 %) and BRAF was the most frequently mutated gene (23 %). Median progression-free survival (PFS) on first-line TKI treatment was 14.6 months (95% CI 9.9-18.4). BRAF mutation positively influenced median PFS, both in the entire TKI-treated cohort (median PFS 34.7 months versus 11.6 months; hazard ratio [HR] 0.29; 95% CI 0.09-0.98; p = 0.03) and in the TKI-treated PTC cohort (n = 22) [log-rank p = 0.086; HR 2.95; 95 % CI 0.81-10.70). However, in TKI-treated patients, PDTC histologic subtype was the only independent prognostic factor for PFS identified in the multivariate analysis (HR 2.36; 95% CI 1.01-5.54; p = 0.048).
CONCLUSION Patients with BRAF-mutant PTC had a significantly longer PFS than BRAF wild-type when treated with TKIs. However, due to the small number of BRAF-mutant patients, further investigations are required, especially to understand the potential positive effect of BRAF mutations in RAIR TC patients while having a negative prognostic impact in RAI-sensitive PTC patients.


Are higher rates of depression in women accounted for by differential symptom reporting?

Abstract:
BACKGROUND The gender difference in prevalence and incidence rates of depression is one of the most consistent findings in psychiatric epidemiology. We sought to examine whether any gender differences in symptom profile might account for this difference in rates.
METHOD This study was a population-based 13-year follow-up survey of community-dwelling adults living in East Baltimore in 1981. Subjects were the continuing participants of the Baltimore Epidemiologic Catchment Area Program. Participants interviewed between 1993 and 1996 with complete data on depressive symptoms and covariates were included (n = 1727). We applied structural equations with a measurement model for dichotomous data (the MIMIC-multiple indicators, multiple causes-model) to compare symptoms between women and men, in relation to the nine symptom groups comprising the diagnostic criteria for major depression, adjusting for several potentially influential characteristics (namely, age, self-reported ethnicity, educational attainment, marital status, and employment).
RESULTS There were no significant gender differences in the self-report of depression symptoms even taking into account the higher level of depressive symptoms of women and the influence of other covariates. For example, women were no more likely to endorse sadness than were men, as evidenced by a direct effect coefficient that was not significantly different from the null [adjusted estimated direct effect of gender on report of sadness = 0.105, 95% confidence interval (-0.113, 0.323)].
CONCLUSION Men and women in this community sample reported similar patterns of depressive symptoms. No evidence that the presentation of depressive symptoms differs by gender was found.


Follow-up of patients with new cardiovascular implantable electronic devices: are experts' recommendations implemented in routine clinical practice?

Abstract:
BACKGROUND A 2008 expert consensus statement outlined the minimum frequency of follow-up of patients with cardiovascular implantable electronic devices (CIEDs).
METHODS AND RESULTS We studied 38 055 Medicare beneficiaries who received a new CIED between January 1, 2005, and June 30, 2009. The main outcome measure was variation of follow-up by patient factors and year of device implantation. We determined the number of patients who were eligible for and attended an in-person CIED follow-up visit within 2 to 12 weeks, 0 to 16 weeks, and 1 year after implantation. Among eligible patients, 42.4% had an initial in-person visit within 2 to 12 weeks. This visit was significantly more common among white patients than black patients and patients of other races (43.0% versus 36.8% versus 40.5%; P<0.001). Follow-up within 2 to 12 weeks improved from 40.3% in 2005 to 55.1% in 2009 (P<0.001 for trend). The rate of follow-up within 0 to 16 weeks was 65.1% and improved considerably from 2005 to 2009 (62.3%-79.6%; P<0.001 for trend). Within 1 year, 78.0% of the overall population had at least 1 in-person CIED follow-up visit.
CONCLUSION Although most Medicare beneficiaries who received a new CIED between 2005 and 2009 did not have an initial in-person CIED follow-up visit within 2 to 12 weeks after device implantation, the rate of initial follow-up improved appreciably over time. This CIED follow-up visit was significantly more common in white patients than in patients of other races.


Serum angiotensin-converting enzyme and frequency of severe hypoglycaemia in Type 1 diabetes: does a relationship exist?

Abstract:
AIMS An association has been described between elevated serum angiotensin-converting enzyme (ACE) and an increased risk of severe hypoglycaemia (SH). To ascertain whether this reported association could be replicated in a different country, it was re-examined in 300 individuals with Type 1 diabetes.
METHODS People with Type 1 diabetes, none of whom was taking renin-angiotensin system blocking drugs, were recruited. Participants recorded the frequency with which they had experienced SH. Glycated haemoglobin (HbA(1c)) and serum ACE were measured. The difference in the incidence of SH between different quartiles of ACE activity and the relationship between serum ACE and SH were examined using non-parametric statistical tests and a negative binomial model.
RESULTS Data were obtained from 300 patients [158 male; HbA(1c) median (range) 8.2% (5.2-12.8%), median age 36 years (16-88); duration of diabetes 14.5 years (2-49)]. The incidence of SH was 0.93 episodes per patient year. The mean incidence of SH in the top and bottom quartiles of ACE activity was 0.5 and 1.7 episodes per patient year, respectively, but this difference was not statistically significant (P = 0.075). Spearman's test showed a very weak, although statistically significant, association between serum ACE level and SH incidence (r = 0.115, P = 0.047). The binomial model also showed a statistically significant (P = 0.002), but clinically weak, relationship between serum ACE and SH.
CONCLUSION The present survey showed a weak relationship between serum ACE and the frequency of SH, the clinical relevance of which is unclear. This limits the proposed role for serum ACE as an index of risk for SH.