Excess Of Patients Research Articles

FOXL2C134W-Induced CYP19 Expression via Cooperation With SMAD3 in HGrC1 Cells.

Germline knockout studies in female mice demonstrated an essential role for forkhead box L2 (FOXL2) in early follicle development, whereas an inducible granulosa cell (GC)-specific deletion of Foxl2 in adults has shown ovary-to-testis somatic sex reprogramming. In women, over 120 different germline mutations in the FOXL2 gene have been shown to cause blepharophimosis/ptosis/epicantus inversus syndrome associated with or without primary ovarian insufficiency. By contrast, a single somatic mutation (FOXL2C134W) accounts for almost all adult-type GC tumors (aGCTs). To test the hypothesis that FOXL2C134W differentially regulates the expression of aGCT markers, we investigated the effect of FOXL2C134W on inhibin B and P450 aromatase expression using a recently established human GC line (HGrC1), which we now show to bear two normal alleles of FOXL2. Neither FOXL2wt nor FOXL2C134W regulate INHBB messenger RNA (mRNA) expression. However, FOXL2C134W selectively displays a 50-fold induction of CYP19 mRNA expression dependent upon activin A. Mechanistically, the CYP19 promoter is activated in a similar way by FOXL2C134W interaction with SMAD3, but not by FOXL2wt. SMAD2 had no effect. Moreover, FOXL2C134W interactions with SMAD3 and with the FOX binding element located at -199 bp upstream of the ATG initiation codon of CYP19 are more sustainable than FOXL2wt. Thus, FOXL2C134W potentiates CYP19 expression in HGrC1 cells via enhanced recruitment of SMAD3 to a proximal FOX binding element. These findings may explain the pathophysiology of estrogen excess in patients with aGCT.

Tumor is an Oxidative Stress Factor in Ovarian Cancer Patients.

To determine the intensity of oxidative stress in ovarian cancer patients and to establish a connection between the presence of the tumor and reactive oxygen species (ROS). Thirty-five patients diagnosed with epithelial ovarian carcinoma stage II-IV between 2010 and 2017, who underwent multimodality treatment (surgery and chemotherapy) were included in the study. ROS measured in dynamic (four determinations between every cycle) were malondialdehyde to evaluate the lipid peroxidation, ceruloplasmin, SH- albumin thiols groups and total antioxidants. Results: There was an increase in the value of ROS: malondialdehyde mean value was 8.1 µmol/100 ml (normal value 4 µmol/100 ml); ceruloplasmin mean value was 144.8U.I. (normal value 120U.I), both showing an active oxidative process in patients with ovarian cancer. A small decrease of the value of thiols (395 vs. 450 µmol/l) and a small increase of total antioxidants was noticed (1.44 vs. 1.4 µmol). All four compounds decrease between the first determination and the fourth one. There was a strong correlation between lipid peroxides levels and ceruloplasmin (Pearson correlation 0.315 p=0.005) and between lipid peroxides and thiols groups (Pearson correlation 0.23 p=0.039). There was a correlation between thiols and antioxidants (Pearson correlation 0.33 p=0.003). Lipid peroxidation and ceruloplasmin were significantly higher in patients with residual disease (p=0.039, p=0.046) emphasizing that the tumor is a generator of oxidative stress. Tumor produces ROS in excess in patients with advanced ovarian adenocarcinoma. Those ROS are corelated and acts as signalling molecules.

Macrolides Blunt Aldosterone Biosynthesis: A Proof-of-Concept Study in KCNJ5 Mutated Adenoma Cells Ex Vivo.

Aldosterone-producing adenoma (APA), a major subtype of primary hyperaldosteronism, the main curable cause of human endocrine hypertension, involves somatic mutations in the potassium channel Kir3.4 (KCNJ5) in 30% to 70% of cases, typically the more florid phenotypes. Because KCNJ5 mutated channels were reported to be specifically sensitive to inhibition by macrolide antibiotics, which concentration dependently blunts aldosterone production in HAC15 transfected with the G151R and L168R mutated channel, we herein tested the effect of clarithromycin on aldosterone synthesis and secretion in a pure population of aldosterone-secreting cells obtained by immunoseparation (CD56+ cells) from APA tissues with/without the 2 most common KCNJ5 mutations. From a large cohort of patients with an unambiguous APA diagnosis, we recruited those who were wild type (n=3) or had G151R (n=2) and L168R (n=2) mutations. We found that clarithromycin concentration dependently lowered CYP11B2 gene expression (by 60%) and aldosterone secretion (by 70%; P<0.001 for both) in CD56+ cells isolated ex vivo from KCNJ5 mutated APAs, although it was ineffective in CD56+ cells from wild-type APAs. By proving the principle that the oversecretion of aldosterone can be specifically blunted in APA cells ex vivo with G151R and L168R mutations, these results provide compelling evidence of the possibility of specifically correcting aldosterone excess in patients with APA carrying the 2 most common KCNJ5 somatic mutations.

Reactive oxygen species in patients with ovarian adenocarcinoma treated with platinum based chemotherapy.

e17047 Background: Ovarian adenocarcinoma (OA) is the most lethal of gynecologic tumors because women generally present with advanced stage disease. Platinum-based chemotherapy plays a pivotal role in OA treatment. The aim of the study was to assess the role of oxygen species in patients with OA and the effects of platinum based chemotherapy on blood redox status. Methods: Twenty three patients with advanced stage IIIC or IV OA who underwent platinum salts chemotherapy were included. Blood sample were collected before treatment, at 21 days (second cycle of chemotherapy) and at 42 days (3rd cycle) and at 63 day (4th cycle) with a platinum salt (cisplatin or carboplatin). Biochemical determination of oxidative stress was made by mesuring lipid peroxidation index (LPI), the enzymatic activity of ceruloplasmin and the thiol albumin groups. Results: Median age at diagnosis was 52 years, and 47.8% of patients presented with stage IIIC and 52.2% with stage IV. Nine patients received for the first time platinum based chemotherapy and 14 received multiple lines of chemotherapy. Response rate after 4 cycles were partial in 30%, stable disease in 57%, and progression disease in 13%. Mean value (± SD) of lipid peroxides was 6.81±1.μmol/100 ml (normal value 0-4), and of ceruloplasmin 156 ± 66 UI (normal value 80-120) which showed an increase of the final products of lipid peroxidation. Thiol mean value was 296±124 μmol/l (normal value 370- 450). The evolution of these reactive oxygen species were monitored during chemotherapy cycles. Decrease of the lipid peroxidation after 1st cycle was noticed, (7, 6.89, 5.87, 6.61), because platinum salt can bind peroxyde and this can be considered a marker of effectiveness of treatment.The thiol levels increased from one cycle to other (233, 311, 384, 393) showing that the cell is trying to contracarete the oxidative stress. Conclusions: Tumors produces reactive oxygen species in excess in patients with advanced OA. Platinum based chemotherapy in patients with OA induces radical formation and the dynamic of these markers may be used to monitor response to treatment.

Clinical characteristics and management of growth hormone excess in patients with McCune-Albright syndrome.

McCune-Albright syndrome (MAS) is a sporadic, postzygotic disease presenting with fibrous dysplasia, cafe-au-lait spots and multiple endocrinopathies. Growth hormone (GH) excess is an uncommon but potentially severe complication of MAS. This study aims to describe the clinical manifestations of GH excess in the context of MAS and analyze the responses of these patients to treatments. Retrospective clinical study. Clinical data from 52 MAS patients were analyzed. Serum GH and IGF1 levels, as well as nadir GH levels after an oral glucose tolerance test and alkaline phosphatase (ALP) levels were determined before and after the treatment. In total, 13 MAS patients (25%) had the complication of GH excess, including 10 males (76.9%). Among them, all had FD, and 6 patients had sphenoidal bone involvement. Visual deficits were present in 8 patients, and hearing deficits were present in 5. Olfactory dysfunction was observed in 3 patients. Evident pituitary adenomas were confirmed in 9 patients by MRI. These patients underwent surgery with or without pretreatment of long-acting somatostatin analogue octreotide, and 6 achieved complete remission. The serum ALP levels decreased significantly after treatment for GH excess. MAS with GH excess is more common in male patients. GH excess can lead to more severe skeletal lesions in MAS patients involving more of the craniofacial bones. Complete trans-sphenoidal complete tumor excision with neuronavigational guidance is effective and could lower ALP levels. LAR is recommended as a preoperative treatment and when patients fail to achieve complete remission after surgery.

Resection of Pheochromocytoma Improves Diabetes Mellitus in the Majority of Patients.

Catecholamine excess in patients with pheochromocytoma often results in impaired glucose tolerance, leading to diabetes mellitus. Little data are available on the long-term effect of surgery on diabetes. The primary aim of this study was to determine the likelihood of diabetes cure after surgery, while secondary objectives were to determine risk factors for development of diabetes preoperatively and persistence of diabetes postoperatively. All patients undergoing surgery for pheochromocytoma from 1996 to 2015 were retrospectively reviewed to identify those with a preoperative diagnosis of diabetes. Demographic and diabetes-specific data were collected. Median follow-up was 52.1months. Overall, 153 patients underwent surgery. Diabetes was seen in 36 (23.4%) patients. Eight patients met the exclusion criteria and were removed from the final analysis, while 22 (78.6%) patients had complete resolution of diabetes. Four patients remained on medication with improved control. Overall, 93.0% of patients had improvement of their diabetes; two patients did not improve. Patients with large, symptomatic tumors were more likely to develop preoperative diabetes, and diabetes was more likely to persist in patients who had an elevated body mass index (BMI). Diabetes was found concurrently with pheochromocytoma in 23% of patients, more often in those with large, symptomatic tumors. The majority of patients had long-term resolution of diabetes after successful resection; however, some patients may continue to require treatment of diabetes after operation, especially those with a higher BMI.

OP.LB01.04] HIGH PREVALENCE OF CARDIAC ELECTRIC ABNORMALITIES IN PATIENTS WITH PHEOCHROMOCYTOMAS AND SECRETING PARAGANGLIOMAS

Objective: Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing tumours of chromaffin cells of the adrenal medulla and extra-adrenal paraganglia. Besides hypertension, they can be at the origin of a wide range of cardiovascular manifestations, including cardiac electric abnormalities such as long QT interval, ventricular tachycardia and torsades de pointe. However, knowledge about PPGL-related arrhythmias is scarce and mostly derived from case reports. The aim of our study was to evaluate the prevalence, nature and reversibility of cardiac electric changes and arrhythmias in patients with PPGLs. Design and method: We retrospectively reviewed the medical records of patients diagnosed with PPGLs at the Cliniques Universitaires Saint-Luc (Brussels) from 1995 to 2015. All patients with secreting PPGLs in whom an electrocardiogram (ECG) was available at the time of diagnosis were eligible. Results: Forty-five patients with secreting PPGLs were identified. The mean age at diagnosis was 48 years (12-72), 40% of patients (n = 18) were males and location of the tumour was adrenal in 87% of cases (n = 39). An ECG was available in 31 patients at the time of diagnosis. Of these, 77% (n = 24) presented at least one electric abnormality. While a positive Sokolow index was found in only 3 patients, non-specific ST-abnormalities were documented in 14 patients (45%), a T-wave inversion in at least two precordial leads in 9 (29%) and a predominant U- wave in 7 patients (23%). Finally, two patients had severe bradycardia (<50 bpm) and extremely long QTc (>600 ms), two patients presented with polymorphic ventricular tachycardia related to a long QT interval at diagnosis that never recurred after surgery, and one patient was diagnosed with paroxystic atrial fibrillation, which resolved after tumour removal. Conclusions: We report a high prevalence (77%) of cardiac electric abnormalities in a retrospective monocentric series of PPGLs. While our findings need confirmation in larger, prospective cohorts, they strongly suggest that cardiac electric abnormalities are an underrecognized, frequent complication of catecholamine excess in patients with PPGLs, and should be an integral part of the work-up and management of these patients.

Growth hormone and risk for cardiac tumors in Carney complex.

Carney complex (CNC) is a multiple neoplasia syndrome that is caused mostly by PRKAR1A mutations. Cardiac myxomas are the leading cause of mortality in CNC patients who, in addition, often develop growth hormone (GH) excess. We studied patients with CNC, who were observed for over a period of 20 years (1995-2015) for the development of both GH excess and cardiac myxomas. GH secretion was evaluated by standard testing; dedicated cardiovascular imaging was used to detect cardiac abnormalities. Four excised cardiac myxomas were tested for the expression of insulin-like growth factor-1 (IGF-1). A total of 99 CNC patients (97 with a PRKAR1A mutation) were included in the study with a mean age of 25.8 ± 16.6 years at presentation. Over an observed mean follow-up of 25.8 years, 60% of patients with GH excess (n = 46) developed a cardiac myxoma compared with only 36% of those without GH excess (n = 54) (P = 0.016). Overall, patients with GH excess were also more likely to have a tumor vs those with normal GH secretion (OR: 2.78, 95% CI: 1.23-6.29; P = 0.014). IGF-1 mRNA and protein were higher in CNC myxomas than in normal heart tissue. We conclude that the development of cardiac myxomas in CNC may be associated with increased GH secretion, in a manner analogous to the association between fibrous dysplasia and GH excess in McCune-Albright syndrome, a condition similar to CNC. We speculate that treatment of GH excess in patients with CNC may reduce the likelihood of cardiac myxoma formation and/or recurrence of this tumor.

PTU-158 The Influence of Social Class on Progression of Barrett’s Oesophagus to Oesophageal Adenocarcinoma: Abstract PTU-158 Table 1

Introduction The incidence of oesophageal adenocarcinoma (OAC) has been rapidly increasing over the last three to four decades in many western nations, including the UK. Barrett’s oesophagus (BO) is the only known precursor condition for OAC. Surveillance of BO may be undertaken with the goal of detecting dysplasia and early neoplasia prior to the development of incurable cancer. The identification of subpopulations of subjects at highest risk of cancer development should allow more effective targeted surveillance. Methods Clinical records of 2896 patients from two centres in the UK, who have consented and registered with the UK Barrett’s Oesophagus Registry (UKBOR), were used for the purpose of this study. Data on patient’s occupation were obtained from hospital records, or from death certificates where available. The most widely used measure of social class in the UK is the ‘Registrar General’s Classification’ which assigns a social class category (I-V with subdivision of class III into III N [non-manual workers] and III M [manual workers] against individual occupation. Social class I are the professionals and higher managers, II and III are junior managers/supervisors, III and IV comprises of semiskilled and manual occupations and those in V are unskilled workers. A Chi-squared goodness of fit test was used to test for significance of the association of social class in both BO and OAC. Results In the BO group, 1824 people had usable information on occupation. Table 1 shows the observed (O) cases of BO and OAC in each of the social classes and the number of expected (E) cases of OAC assuming an equal proportion of social class developed OAC (p-value – 0.003) The O/E results demonstrate an excess of patients progressing to OAC in social class III M, and a lower than expected number of cases in social classes I, III N and V. Conclusion Our study shows that more OAC is observed in BO patients in social class III M than expected whereas fewer are observed in social class I, IIIN and V than expected. References 1 Jansson C, Johansson AL, Nyren O, et al . Socioeconomicfactors and risk of esophageal adenocarcinoma: a nationwide Swedish case-control study. Cancer Epidemiol Biomarkers Prev 2005; 14 : 1754–1761. 2 Islami F, Kamnagar F, Nasrollahzadeh D, et al . Socio-economic status and oesophageal cancer: results from a population based case-control study in a high risk area. Int J Epidemiol 2009; 38 :978–988. Disclosure of Interest None Declared

Serum Adiponectin Level as a Predictor of Subclinical Cushing's Syndrome in Patients with Adrenal Incidentaloma.

Subclinical Cushing's syndrome (SCS) is a condition of slight but chronic cortisol excess in patients with adrenal incidentaloma (AI) without typical signs and symptoms of Cushing's syndrome. Adiponectin has potent roles in modulating energy balance and metabolic homeostasis and acts in opposition to glucocorticoids. This study aimed to evaluate adiponectin level in SCS and nonfunctional AI (NAI) patients and its relation with metabolic parameters. Patients with AI (n = 40) and metabolically healthy controls (n = 30) were included. In AI patients and controls, detailed medical history assessment, physical examinations, anthropometric measurements, and laboratory measurements were performed. Age, body mass index, waist circumference, and lipid profiles were significantly higher and waist-to-hip ratio and adiponectin level were significantly lower in the AI patients than in the controls. The midnight cortisol and urinary free cortisol levels were significantly higher in the SCS patients (n = 8) than in the NAI patients (n = 32). Adiponectin level of the SCS group was significantly lower than those of the NAI and control groups. The sensitivity and specificity for an adiponectin level of ≤13.00 ng/mL in predicting the presence of SCS were 87.5% and 77.4%, respectively. In conclusion, adiponectin is valuable in predicting the presence of SCS in AI patients.

Chapter 44 - Neuroendocrine disorders: pituitary imaging

Significant advances in pituitary imaging have taken place in the past several decades, including the introduction of magnetic resonance imaging (MRI). This imaging modality has vastly improved our ability to detect and characterize sellar masses and more accurately characterize the extent and spread of lesions in and around the sella. Intraoperative MRI may help improve the completeness of resection of sellar masses. Other imaging modalities, including magnetic resonance angiography, computed tomography (CT), and CT angiography, have an important role in specific cases. Interventional methods, including bilateral inferior petrosal sinus sampling, may establish the pituitary origin of corticotropin (ACTH) excess in patients with ACTH-dependent Cushing's syndrome. Pituitary imaging should be obtained in patients with pituitary hormone excess, hypopituitarism, or mass effect in the sella. Despite rapid advances in pituitary imaging, there are several diagnostic challenges remaining. Future research may help improve the radiographic detection of small sellar lesions, such as ACTH-secreting adenomas causing Cushing's disease, accurately characterize the type and extent of sellar pathologies, and provide prognostic information regarding their growth potential.

P3-21: High prevalence of cardiac electric abnormalities in patients with pheochromocytomas and secreting paragangliomas

Background Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing tumours of chromaffin cells of the adrenal medulla and extra-adrenal paraganglia. Besides hypertension, they can be at the origin of a wide range of cardiovascular manifestations, including cardiac electric abnormalities such as long QT interval, ventricular tachycardia and torsades de pointe. However, knowledge about PPGL-related arrhythmias is scarce and mostly derived from case reports. The aim of our study was to evaluate the prevalence, nature and reversibility of cardiac electric changes and arrhythmias in patients with PPGLs. Methods We retrospectively reviewed the medical records of patients diagnosed with PPGLs at the Cliniques Universitaires Saint-Luc (Brussels) from 1995 to 2015. All patients with secreting PPGLs in whom an electrocardiogram (ECG) was available at the time of diagnosis were eligible. Results Forty-five patients with secreting PPGLs were identified. The mean age at diagnosis was 48 years (12-72), 40% of patients (n=18) were males and location of the tumour was adrenal in 87% of cases (n=39). An ECG was available in 31 patients at the time of diagnosis. Of these, 77% (n=24) presented at least one electric abnormality. While a positive Sokolow index was found in only 3 patients, non-specific ST-abnormalities were documented in 14 patients (45%), a T-wave inversion in at least two precordial leads in 9 (29%) and a predominant U- wave in 7 patients (23%) Furthermore, a corrected QT interval prolongation (>450ms) was present in 55% of patients (n=17, mean: 528ms±93ms). In all nine patients with QTc prolongation at diagnosis in whom a follow-up ECG was available, QTc normalized after surgery (QTc.: 420±20ms after surgery vs. 523±50ms at baseline, p 600ms), two patients presented with polymorphic ventricular tachycardia related to a long QT interval at diagnosis that never recurred after surgery, and one patient was diagnosed with paroxystic atrial fibrillation, which resolved after tumour removal. Conclusions We report a high prevalence (77%) of cardiac electric abnormalities in a retrospective monocentric series of PPGLs. While our findings need confirmation in larger, prospective cohorts, they strongly suggest that cardiac electric abnormalities are an underrecognized, frequent complication of catecholamine excess in patients with PPGLs, and should be an integral part of the work-up and management of these patients.

Correlation of Pain and Fluoride Concentration in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Voriconazole

Supportive care guidelines recommend antimold prophylaxis in hematopoietic stem cell transplant (HSCT) recipients deemed to have high risk for invasive fungal infection, leading to long-term use of voriconazole after allogeneic HSCT in patients who remain immunocompromised. Voriconazole has been associated with periostitis, exostoses, and fluoride excess in patients after solid organ transplantation, HSCT, and leukemia therapy. The aims of this study were to describe the frequency and clinical presentation of patients presenting with pain and fluoride excess among allogeneic HSCT patients taking voriconazole, to identify when a plasma fluoride concentration was measured with respect to voriconazole initiation and onset of pain, and to describe the outcomes of patients with fluoride excess in the setting of HSCT. A retrospective review was conducted of all adult allogeneic HSCT patients receiving voriconazole at Mayo Clinic in Rochester, Minnesota, between January 1, 2009 and July 31, 2012. Of 242 patients included, 32 had plasma fluoride measured to explore the etiology of musculoskeletal pain. In 31 patients with fluoride measurement while on voriconazole, 29 (93.5%) had elevated levels. The median plasma fluoride was 11.1 μmol/L (range, 2.4 to 24.7). The median duration of voriconazole was 163 days (range, 2 to 1327). The median time to fluoride measurement was 128 days after voriconazole initiation (range, 28 to 692). At 1 year after the start of voriconazole after HSCT, 15.3% of patients had developed pain associated with voriconazole use and 35.7% developed pain while on voriconazole after 2 years. Of the patients with an elevated fluoride level, 22 discontinued voriconazole; pain resolved or improved in 15, stabilized in 3, and worsened in 4 patients. Ten patients continued voriconazole; pain resolved or improved in 7, was attributable to alternative causes in 2, and undefined in 1. Serum creatinine, estimated glomerular filtration rate, alkaline phosphatase, and voriconazole concentration did not predict for fluoride excess and associated pain. Periostitis due to fluoride excess is a common adverse effect of voriconazole that should be considered in patients presenting with pain and is often reversible after drug discontinuation. Alternative antifungal agents with a lower risk for fluoride excess should be considered in patients receiving voriconazole who develop fluoride excess and pain.

ARMC5 mutation analysis in patients with primary aldosteronism and bilateral adrenal lesions.

Idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia is the most common subtype of primary aldosteronism (PA). The pathogenesis of IHA is still unknown, but the bilateral disease suggests a potential predisposing genetic alteration. Heterozygous germline mutations of armadillo repeat containing 5 (ARMC5) have been shown to be associated with hypercortisolism due to sporadic primary bilateral macronodular adrenal hyperplasia and are also observed in African-American PA patients. We investigated the presence of germline ARMC5 mutations in a group of PA patients who had bilateral computed tomography-detectable adrenal alterations. We sequenced the entire coding region of ARMC5 and all intron/exon boundaries in 39 patients (37 Caucasians and 2 black Africans) with confirmed PA (8 unilateral, 27 bilateral and 4 undetermined subtype) and bilateral adrenal lesions. We identified 11 common variants, 5 rare variants with a minor allele frequency <1% and 2 new variants not previously reported in public databases. We did not detect by in silico analysis any ARMC5 sequence variations that were predicted to alter protein function. In conclusion, ARMC5 mutations are not present in a fairly large series of Caucasian patients with PA associated to bilateral adrenal disease. Further studies are required to definitively clarify the role of ARMC5 in the pathogenesis of adrenal nodules and aldosterone excess in patients with PA.

Increased serum chemerin concentrations in patients with polycystic ovary syndrome: Relationship between insulin resistance and ovarian volume

BackgroundChemerin has been linked to adiposity, and insulin resistance (IR) which are the common characteristics of polycystic ovary syndrome (PCOS). Chemerin also shows inhibitory action on follicular steroidogenesis. We investigated the associations between chemerin and IR or polycystic ovary morphology in patients with PCOS. MethodsA total of 148 women with newly diagnosed PCOS using Rotterdam criteria and 88 healthy individuals were enrolled. The recruited patients with PCOS were further stratified by tertiles of serum chemerin concentrations as follows: Group 1 (<24.79ng/ml), Group 2 (24.79–30.27ng/ml), and Group 3 (>30.27ng/ml). ResultsCompared to controls, women with PCOS in each tertile had higher serum chemerin concentrations. By linear regression analysis, homeostasis model assessment-insulin resistance and ovarian volume showed significant associations with chemerin after adjusting for confounding factors (β=0.257, P=0.028; β=0.276, P=0.005, respectively). The odds ratios (ORs) for ovarian volume excess gradually increased across increasing tertiles of chemerin in the adjusted model [Group 1: reference; Group 2: OR 1.602; 95% confidence interval (CI): 1.170–2.194; Group 3: OR 1.857; 95% CI: 1.335–2.583]. ConclusionsPatients with PCOS showed increased serum chemerin concentrations as compared to healthy women. Individuals with higher chemerin tended to have higher risk for ovarian volume excess in patients with PCOS, regardless of adiposity.

The attributable mortality of delirium in critically ill patients: prospective cohort study

Objective To determine the attributable mortality caused by delirium in critically ill patients.Design Prospective cohort study.Setting 32 mixed bed intensive care unit in the Netherlands, January 2011 to July 2013.Participants...

Radiation Exposure During Cardiac Catheterisation is Similar for Both Femoral and Radial Approaches

Radial approach invasive coronary angiography has been shown to be superior to the femoral approach in terms of reducing vascular access complications and improving patient comfort. However, one major limitation has been the perception of higher patient radiation exposure, with guidelines recommending 7mSv as an appropriate average effective dose (E) for routine coronary angiography. Therefore, we sought here to assess differences in radiation exposure between the femoral and radial access routes in patients undergoing diagnostic coronary angiography with or without angioplasty (CA +/- PCI), as performed by two operators, experienced in both techniques. Consecutive patients (n=870) from July 2011-December 2012, undergoing routine CA +/- PCI at Royal Prince Alfred Hospital, Sydney by two experienced interventional cardiologists were identified. Radiation doses were automatically recorded as dose area products (DAPs) at procedure time and converted into E using a conversion factor of 0.18 mSv/(Gycm2), as validated by the National Radiological Protection Board (NRPB). Of the 870 patients, 598 underwent diagnostic CA (347 femoral, 251 radial); and 272 underwent CA+ PCI (179 femoral, 93 radial). The mean age of the patients was 65±12 years and the majority (n=617, 71%) were male. Both groups were well matched with respect to baseline demographics, clinical presentation and angiographic characteristics, though there was an excess of patients with a history of coronary grafts in the femoral group, due to operator preference. In the patients who underwent diagnostic CA, there was no significant difference in the average effective radiation dose for femoral versus radial arterial access (E=7.9±8.2 vs. 8.3±10.6mSv; p=0.66). Similarly, there was also no difference in average effective radiation dose for femoral versus radial arterial access in patients undergoing CA+PCI (E=13.2±8.1 vs E=14.4±8.3 mSv; p=0.26). In our high volume cardiac catheterisation laboratory, radiation doses for routine angiography were near UNSC targets. Patient radiation exposure was comparable between femoral and radial approaches, for both CA and CA +/- PCI. Thus, our results allay concerns that radial cardiac catheterisation might be associated with greater radiation exposure.

Prevalence of nursing diagnosis of fluid volume excess in patients undergoing hemodialysis

To identify the prevalence of nursing diagnosis of fluid volume excess and their defining characteristics in hemodialysis patients and the association between them. Cross-sectional study conducted in two steps. We interviewed 100 patients between the months of December 2012 and April 2013 in a teaching hospital and one hemodialysis clinic. The inference was performed by diagnostician nurses between July and September 2013. The diagnostic studied was identified in 82% of patients. The characteristics that were statistically associated: bounding pulses, pulmonary congestion, jugular vein distention, edema, change in electrolytes, weight gain, intake greater than output and abnormal breath sounds. Among these, edema and weight gain had the highest chances for the development of this diagnostic. The analyzed diagnostic is prevalent in this population and eight characteristics presented significant association.

Long-term course after initial iron removal of iron excess in patients with dysmetabolic iron overload syndrome

Initial venesection therapy in dysmetabolic iron overload syndrome (DIOS) was shown to improve insulin resistance. However, no data are available on the long-term outcome of iron store, thus questioning the relevance of maintenance therapy. The aim of the study was to describe the long-term evolution of iron overload after successful iron removal in patients with DIOS. Patients diagnosed with DIOS from 1998 to 2003 and having completed venesection therapy were proposed an outpatient visit in 2009. Inclusion criteria were as follows: confirmation of the DIOS diagnosis, absence of iron-related treatment or bloodletting since the end of the initial venesection treatment, at least 2 years of follow-up since last phlebotomy. Clinical and biological data were recorded at diagnosis and at inclusion. A total of 58 patients were included. The mean liver iron content at diagnosis was 80±43 µmol/g and the mean amount of iron removed was 2.2±1.2 g. The mean follow-up time was 71±23 months since end of treatment. At inclusion, 64% of patients had recurrence of iron overload. Serum ferritin at diagnosis was the only parameter associated with recurrence of iron overload. In patients with DIOS, the course of iron loading after initial iron removal supports periodical follow-up to detect those patients with recurrence of iron overload who could benefit from maintenance therapy.

Relationship between copper doses in parenteral nutrition mixtures, serum copper, erythrocyte copper levels, ceruloplasmin and C-reactive protein, in critically ill patients

Summary Background and aims There is no consensus on the recommended amounts of copper to be administered to critically ill patients on parenteral nutrition, as requirements are variable and very difficult to determine in different disease states. The objective of this study was to assess copper status of critically ill patients on total parenteral nutrition in order to prevent inadequate copper administration. Methods The study comprised adult patients (20 males and 10 females) requiring total parenteral nutrition for 4–21 days, because of pancreatitis ( n = 5) or after major abdominal surgery ( n = 25). Parenteral nutrition was discontinued when the patient tolerated enteral or oral feeding. The following parameters were determined throughout the study (4–21 days): total copper administered by parenteral nutrition, serum copper, erythrocyte copper (Atomic Absorption Spectrometry); serum ceruloplasmin (Ferroxidase activity) and C-reactive protein levels (Immunoturbidimetry, Latex HS). Results Total copper administered in parenteral nutrition ranged between 0.03 and 3.8 mg/d, and was higher than prescribed amounts due to copper contamination of individual components. The amount of copper given in parenteral nutrition correlated with changes in erythrocyte copper, but not with changes in serum copper, ceruloplasmin, or C-reactive protein. Conclusions Variations in erythrocyte copper levels showed significant correlation with the amount of copper administered daily in parenteral nutrition mixtures, and this biochemical indicator could be useful to monitor copper deficiency or excess in patients on parenteral nutrition. It is noteworthy that copper delivery above 1.2 mg/d was frequent and prompts such monitoring.