Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II.

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

Session 2: Mutational discordance: the big challenge in personalized treatments - any solutions?

The great challenge for oncologists treating patients who are developing or progressing with metastatic disease is to be able to offer a truly personalized and targeted therapy that can have an early and meaningful effect on the course of the disease. At present the known molecular markers are limited in their frequency and reliability in determining the use of newer chemotherapies. Professor Eng discusses the challenges faced in ensuring timely and effective treatments based on the molecular profile of the tumour and the potential role of real-time analysis of mutational changes in the tumour when progression occurs.

Photothermal cancer therapy by gold-ferrite nanocomposite and near-infrared laser in animal model.

Surface plasmon resonance effect of gold nanostructures makes them good candidates for photothermal therapy (PTT) application. Herein, gold-ferrite nanocomposite (GFNC) was synthesized and characterized as a photothermal agent in PTT. The aim of this study was to investigate the effect of GFNC upon laser irradiation on treatment of cancer in mice bearing melanoma cancer. Thirty mice received 1.5 × 10(6) B16/F10 cells subcutaneously. After 1 week, the mice bearing solid tumor were divided into four groups: control group (without any treatment), laser group (received laser irradiation without GFNC injection), GFNC group (only received intratumorally GFNC), and GFNC + laser group (received intratumorally GFNC upon laser irradiation). In GFNC + laser group, 200 µL of fluid, 1.3 × 10(-7) mol L(-1) gold nanoparticles, was injected intratumorally and immediately the site of tumor was exposed to continuous wave diode laser beam (808 nm, 1.6 W cm(-2)) for 15 min. All mice but four were euthanized 24 h after treatment to compare the necrotic surface area histologically by using measuring graticule. Statistical analyses revealed significant differences in necrosis extent for GFNC + laser group, compared to other groups. Four subjects (control group and GFNC + laser group, two mice each) were kept for longitudinal study. Histological analyses and tumor volume measurements of the four subjects indicated that tumor in GFNC + laser group was controlled appropriately. It was concluded that combining an 808-nm laser at a power density of 1.6 W cm(-2) with GFNC has a destruction effect in melanoma cancer cells in an animal model.

Analysis of follicular fluid total phospholipids in women undergoing in-vitro fertilisation.

Follicular fluid (FF) samples were obtained from 100 patients referred to the University Hospital. A total of 79 subjects underwent IVF and the remaining 21 underwent ICSI. The levels of apoA-I and total phospholipid were measured using turbidometric and colorimetric phosphorus assays, respectively. Correlation analysis showed a significant inverse association of total phospholipid in FF with fertilisation ratio (r = -0.24, p = 0.04). Furthermore, the ratio of phospholipid/apoA-I in patients with a percentage of fertilised oocytes ≤ 50% was significantly higher (> 2.5%, p < 0.05) than in those with higher percentages of fertilised oocytes. The amounts of phospholipid and phospholipid/apoA-I ratio in FF were associated negatively to the percentage of oocyte fertilisation. Therefore, the change in the phospholipid and phospholipid/apoA-I ratio of FF might be regarded as indicators of female fertility.

Tissue fatty acid composition in human urothelial carcinoma.

Bladder cancer cells appear to have an altered lipid metabolism as evidenced by modulated lipogenic enzymes. The aim of this study is to investigate differences in tissue fat composition between malignant and adjacent normal urinary bladder tissue. Normal-appearing and malignant bladder tissues were collected from 31 patients with high-grade (Ta) urothelial carcinoma during transurethral resection (TUR). The fatty acid composition in the tissue was determined by gas liquid chromatography. In the bladder cancer tissue, levels of stearic acid (18:0; P = 0.01) and oleic acid (18:1n-9; P = 0.03) were higher, and the level of arachidonic aid (20:4n-6; P < 0.001) was lower than that in the normal-appearing bladder. Overall, bladder cancer tissue showed a significant reduction in total n-6 polyunsaturated fatty acid (-15.1%; P < 0.001). The change in the fatty acid composition may be regarded as an indicator of altered lipid metabolism occurring in vivo during human bladder tumourigenesis.

Investigation the Effect of Low, Medium and High Dose of X-Radiation on the Expression of E-cadherin in Colorectal Cancer Cell Line.

BACKGROUND: Radiotherapy has become a part of therapeutic process of more than 50 percent of patients suffering from cancer. However, recent studies have shown that radiation therapy might affect the expression of adhesive molecule related genes such as E-cadherin and cause cancer cells to move and migrate. Besides, various studies have reported that the expression of E-cadherin changes differently after radiation treatment. There are several studies which showed the loss of E-cadherin function after radiation; however, this reduction has not been observed in others. OBJECTIVE: This study aims to investigate the effect of different radiation doses of X-ray on changes that might occur in the expression of E-cadherin gene in colorectal cancer cell line HT-29. MATERIAL AND METHODS: In this experimental study, the cells cultured in flasks were irradiated with X- rays in different doses, including 0.1, 2.5, 5, and 10 Gy; then, the expression of E-cadherin gene was measured using real-time PCR. RESULTS: The expression of E-cadherin did not change significantly in post-irradiated HT-29 cell line after different radiation doses of X-ray. CONCLUSION: The results showed that low, medium and high doses of X- radiation did not change the expression of E-cadherin gene in HT-29 cancer cells. However, it has been reported that radiation mostly downregulated the expression of E-cadherin and mediated metastasis formation and invasiveness in different cancer cell lines. Therefore, further studies need to be conducted to investigate the effects of radiation dose on the molecular pathways contributing to regulation of E-cadherin in HT-29 cell line.

Mandibular Trabecular Bone Analysis Using Local Binary Pattern for Osteoporosis Diagnosis.

BACKGROUND: Osteoporosis is a systemic skeletal disease characterized by low bone mineral density (BMD) and micro-architectural deterioration of bone tissue, leading to bone fragility and increased fracture risk. Since Panoramic image is a feasible and relatively routine imaging technique in dentistry; it could provide an opportunistic chance for screening osteoporosis. In this regard, numerous panoramic derived indices have been developed and suggested for osteoporosis screening. Jaw trabecular pattern is one of the main bone strength factors and trabecular bone pattern assessment is important factor in bone quality analysis. Texture analysis applied to trabecular bone images offers an ability to exploit the information present on conventional radiographs. OBJECTIVE: The purpose of this study was to evaluate the relationship between Jaw trabecular pattern in panoramic image and osteoporosis based on image texture analyzing using local binary pattern. MATERIAL AND METHODS: An experiment is evaluated in this paper based on a real hand-captured database of panoramic radiograph images from osteoporosis and non-osteoporosis person in Namazi Hospital, Shiraz, Iran .An approach is proposed for osteoporosis diagnosis consisting of two steps. First, modified version of local binary patterns is used to extract discriminative features from jaw panoramic radiograph images. Then, classification is done using different classifiers. RESULTS: Comparative results show that the proposed approach provides classification accuracy about 99.6%, which is higher than many state-of-the-art methods. CONCLUSION: High classification accuracy, low computational complexity, multi-resolution and rotation invariant are among advantages of our proposed approach.

Burnout in hospital nurses: a comparison of internal, surgery, psychiatry and burns wards.

INTRODUCTION: Burnout is a phenomenon in which the cumulative effects of a stressful work environment gradually overwhelm the defenses of staff members, forcing them to withdraw psychologically. This study compared the levels of burnout among nurses in different nursing specialties. MATERIALS AND METHODS: The sample of the study consisted of all the nurses working in all public hospitals in Shiraz, Iran who were graduates of either technological educational institutions or universities and had experienced clinical nursing practice for at least 1 year. Using Maslach Burnout Inventory and General Health Questionnaire (28-item version), we identified the psychiatric morbidity and burnout among nurses. RESULTS: Study results indicated that nurses of psychiatry wards showed significantly higher levels of emotional exhaustion and depersonalization in comparison with nurses working in other wards, and burn wards nurses showed significantly higher levels of personal accomplishment. Also, nurses who were single were more emotionally exhausted. CONCLUSION: Different clinical working environments appear to have an impact on the development of nurses' burnout.

"Triple M" Effect: A Proposed Mechanism to Explain Increased Dental Amalgam Microleakage after Exposure to Radiofrequency Electromagnetic Radiation.

A large body of evidence now indicates that the amount of mercury released from dental amalgam fillings can be significantly accelerated by exposure to radiofrequency electromagnetic fields (RF-EMFs) such as common mobile phones and magnetic resonance imaging (MRI). Studies performed on the increased microleakage of dental amalgam restorations after exposure to RF-EMFs have further supported these findings. Although the accelerated microleakage induced by RF-EMFs is clinically significant, the entire mechanisms of this phenomenon are not clearly understood. In this paper, we introduce "Triple M" effect, a new evidence-based theory which can explain the accelerated microleakage of dental amalgam fillings after exposure to different sources of electromagnetic radiation. Based on this theory, there are saliva-filled tiny spaces between amalgam and the tooth. Exposure of the oral cavity to RF-EMFs increases the energy of these small amounts of saliva. Due to the small mass of saliva in these tiny spaces, a small amount of energy will be required for heating. Moreover, reflection of the radiofrequency radiation on the inner walls of the tiny spaces causes interference which in turn produces some "hot spots" in these spaces. Finally, formation of gas bubbles in response to increased temperature and very rapid expansion of these bubbles will accelerate the microleakage of amalgam. Experiments that confirm the validity of this theory are discussed.

Design and Production of Two-piece Thyroid-neck Phantom by the Concurrent Use of Epoxy Resin and Poly(methyl methacrylate) Soft Tissue Equivalent Materials.

The aim of this report is to present a new two-piece thyroid-neck phantom produced by the concurrent use of epoxy resin and poly(methyl methacrylate) (PMMA: plexiglass) soft tissue equivalent materials. Accordingly, mass attenuation coefficients of the epoxy resin and the plexiglass compounds were obtained from simulation (NIST XCOM 3.1) and measurements (practical dosimetry) and compared to those related to human soft tissue (ICRU 44). The thyroid-neck phantom and thyroid gland dimensions were derived from scientific references and the atlas of human anatomy, respectively. The thyroid phantom was designed by CATIA V5R16 software and produced by the epoxy resin compound by three-dimensional printer. Other organs were designed by ProNest software and made by the plexiglass sheets by CNC laser cutting machine. The mass attenuation coefficients for the epoxy resin (50 keV- 20 MeV) and the plexiglass (0-20 MeV) were comparable to human soft tissue (ICRU 44), all with standard relative deviation beneath 5%. In addition, the SPECT images indicated the similarity between human thyroid tissue and its phantom. In conclusion, this study proves the feasibility and reliability of epoxy resin application in the production of two-piece thyroid-neck phantom. This phantom can be applied in the calibration of gamma camera systems, dosimetry and gamma spectrometry in the nuclear medicine field.

Effect of hypertension on transplant kidney function: three year of follow-up.

BACKGROUND: Hypertension significantly increases the risk for chronic graft loss and accelerates the deterioration of transplanted kidney function. Aggressive control of blood pressure (BP) is recommended in the posttransplant period when maintenance levels of immunosuppressive drugs are achieved. The aim of this study was to investigate whether the improved control improved the graft survival. METHODS: We compared transplant kidney function in two groups of hypertensive patients matched for age, gender, donor-recipient relation, primary disease, early posttransplant course, and immunosuppressant and hypertensive therapy during 3 years follow-up. The patients were divided into satisfactory and unsatisfactory controlled blood pressure. Group 1 consisted of 98 patients with satisfactory BP control (arterial pressure <160/90 mmHg) and group 2, 98 patients with unsatisfactory BP control. RESULTS: The mean through levels of cyclosporine in whole blood were similar in both groups and did not exceed 185 ng/mL. A slow but significant increase in mean creatinine levels was observed among group 2 during 3 years follow-up, whereas, among group 1, graft function remained stable. Cardiovascular events were observed only in group 2: stroke in one patient and death because of heart failure in one patient. Factors which correlated with development of post transplant hypertension were age, gender, duration of disease before transplant, and underlying disease. CONCLUSION: Lowering BP, even several years posttransplantation, was associated with improved graft and patient survival in renal transplant recipients.

Modification of Source Strength in Low-Dose-Rate Lung Brachytherapy with 125I and 103Pd Seeds.

BACKGROUND: A new treatment approach for most patients who have undergone early stage non-small-cell lung carcinoma (NSCLC) is wedge resection plus permanent implant brachytherapy. However, the specification of dose to medium at low energies especially in heterogeneous lung is unclear yet. OBJECTIVE: The present study aims to modify source strength for different configurations of 125I and 103Pd seeds used in lung permanent implant brachytherapy. METHODS: Different arrays of 125I and 103Pd seeds were simulated by MCNPX code in protocol-based water vs. actual 3D lung environments. Absorbed dose was, then, scored in both mediums. Dose differences between both environments were calculated and source strength was modified for the prescription point. In addition, lung-to-water absorbed dose ratio was obtained and presented by precise equations. RESULTS: Due to significant differences in prescription dose, source strength was modified 16%-19% and 37%-43% for different configurations of 125I and 103Pd seeds, respectively. In addition, depth-dependent dose differences were observed between the actual lung and protocol-based water mediums (dose difference as a function of depth). CONCLUSION: Modification of source strength is essential for different arrangements of 125I and 103Pd seeds in lung implantation. Modified source strength and presented equations are recommended to be considered in future studies based on lung brachytherapy.

Incidence of cardiovascular risk factors and complications before and after kidney transplantation.

BACKGROUND: Cardiovascular disease is a leading cause of death after renal transplantation with an incidence considerably higher than that in the general population. The aim of this study was to evaluate the association of atherosclerotic cardiovascular complications and the prevalence of cardiovascular risk factors prior to and following transplantation. PATIENTS AND METHODS: Atherosclerotic cardiovascular diseases including coronary artery disease, as well as cerebral and peripheral vascular disease, and cardiovascular risk factors pre- and posttransplantation were analyzed in 500 renal transplant recipients between 1988 and 1992. The mean recipient age at transplantation was 45 +/- 12 years, with 58% men and 7% diabetics. RESULTS: Following transplantation 11.7% developed atherosclerotic cardiovascular diseases, the majority being coronary artery disease (9.8%). Comparison of the risk factors before and after transplantation showed the increased prevalence of systemic hypertension to be 67% to 86%, of diabetes mellitus, 7% to 16%, and obesity, with a body mass index > 25 kg/m2 from 26% to 48%, whereas the number of smokers was halved to 20%. The triglycerides decreased significantly (from 235 +/- 144 mg/dL to 217 +/- 122 mg/dL) but the total and high-density lipoprotein (HDL) cholesterol rose significantly (from 232 +/- 65 mg/dL to 273 +/- 62 mg/dL and from 47 +/- 29 mg/dL to 56 +/- 21 mg/dL, respectively). The low-density lipoprotein (LDL) cholesterol increase was insignificant (from 180 +/- 62 mg/dL to 189 +/- 53 mg/dL). Upon univariate analysis, cardiovascular diseases were significantly associated with male gender; age over 50 years; diabetes mellitus (DM); smoking; total cholesterol > 200 mg/dL; LDL cholesterol > 180 mg/dL; HDL cholesterol < 55 mg/dL; fibrinogen > 350 mg/dL; body mass index > 25 kg/m2; and more than two antihypertensive agents per day. The Cox proportional hazards model revealed DM with a relative risk (RR) of 4.3; age > 50 years (RR = 2.7); body mass index > 25 kg/m2 (RR = 2.6); smoking (RR = 2.5); and LDL cholesterol > 180 mg/dL (RR = 2.3) as independent risk factors. CONCLUSIONS: The high incidence of cardiovascular disease following renal transplantation is mainly due to a high prevalence and accumulation of classical risk factors before and following transplantation. The treatment of risk factors must be introduced early in the course of renal failure and continued following transplantation. Future prospective studies should evaluate the success of treatment regarding reduction of cardiovascular morbidity and mortality in this high-risk population.

Predictors of cardiovascular events and associated mortality of kidney transplant recipients.

BACKGROUND: Cardiovascular disease is the most common cause of death after renal transplantation. Furthermore, acute coronary syndrome (ACS) attributable to coronary artery disease (CAD) accounts for the majority of deaths due to cardiovascular disease posttransplant. Although renal transplantation is the treatment of choice for end-stage renal disease, understanding the causes of graft and patient loss is exceedingly important to improve outcomes. METHODS: This observational study included 1200 patients who underwent a kidney transplant between 1988 and 2003. The outcome was the occurrence of an ACS event within a maximum of 15 years after renal transplantation. RESULTS: Of all 215 deaths, 28.3% were caused by complications of CAD, the most common cause of death at our center. On multivariate analysis, diabetes (P = .005), prior transplant (P = .047), body mass index (BMI) at the time of transplant (P = .01), cholesterol level (P = .012), and low-density lipoprotein (LDL) level (P = .007) during 3 years after transplant were associated with early ACS. In conclusion, diabetes, prior transplant, BMI, cholesterol, and LDL were significantly associated with early ACS highlighting the importance of improved screening and perioperative management.

Complications of arteriovenous fistula in dialysis patients.

Repeated access to the circulation is essential to perform adequate maintenance hemodialysis (HD). Dysfunction of fistulae is the most common reason for a second intervention and recurrent hospitalization. The aim of this study was to evaluate the complications of HD fistulas seeking to evaluate the impact of age, site of arteriovenous fistula (AVF) (proximal or distal), side (left or right), and history of previous vascular access. We evaluated the clinical complications in 273 patients from the beginning of the use of the current access using the history and physical examination obtained at every dialysis session. We performed further investigations including doppler ultrasound or spiral computed tomography to confirm the clinical diagnosis. Of our patients, 40% had diabetes mellitus as the cause of end-stage renal disease. Almost half (49%) the patients dialyzed through an AVF and 13% with a catheter. One hundred eighty-four cases (67.6%) experienced complications. Of 145 cases that had elbow AVFs, 103 cases (71%) had complications; of 128 cases with wrist AVFs, 80 cases (62.5%) had complications. There were 115 (62.5%) complicated cases among 185 patients with left AVFs, and 69 (78%) among 88 patients with right AVFs. The rate of AVF complications increased with age. The 1-year survival rate was 94%. We did not observe any significant difference between AVF complications in patients with diabetes mellitus or hypertension as the underlying cause of renal failure. Mean cholesterol plasma level did not differ significantly between the patients with and without AVF complications. Mean hematocrit levels were not significantly different between the two groups. However, mean EPO weekly dose was significantly higher among the group of patients with AVF complications. We did find that rate of complications increased with age (P<.05). Our results showed that the frequency of complications was higher among patients with elbow and right-side AVFs, and also among patients with a history of a previous failed shunt but no significant relationship was observed between these variables (P>.05).

Comparison of spousal with other donor groups: Study of a single center.

In coping with the shortage of living-related and cadaveric donor groups for renal transplantation, and in the fear of organ marketing, spousal donors are considered an invaluable potential source. Survival rates have been reported to be as high as even some related groups. This study evaluated 1039 renal transplantations up to 2003. Patient survival rates in different donor groups were determined using the Kaplan-Meier method. The 3-year patient survival rates were 93% for kidneys from 61 spouses; 92% for kidneys from 433 living-related donors; 91% for kidneys from 427 living-unrelated (excluding spouses) donors; and 90.5% for 118 cadaveric kidneys. Such results were consistent with many other reports which consistently showed that spousal donors were at least as good as living-related donors, representing a reliable source in cases of organ shortage. The high survival rate of spousal donors is probably related to their strong emotional support.

How to decrease cardiovascular mortality in renal transplant recipients.

Cardiovascular disease is the leading cause of death following renal transplantation, accounting for 40% to 55% of all deaths. An analysis in our center showed a 15% mortality in a cohort of renal transplant recipients followed for an average of 10 years. Various contributing risk factors of cardiovascular diseases in transplant recipients such as tobacco use, hypertension, hyperlipidemia, hereditary risk, diabetes, physical inactivity, obesity, dialysis duration, hyperuricemia, proteinuria, hyperhomocysteinemia, hyperparathyroidism, anemia; C-reactive protein level, and immunosuppressive regimen as well as some rare risk factors, such as cytomegalovirus infection, were evaluated in a population of 1200 kidney transplant recipients. Also we introduced methods for early detection, monitoring, and follow-up of proven risk factors of cardiovascular disease.

Long-term results of renal transplantation: A single-center analysis of 1200 transplants.

The present study is a report of long-term results of the first 1200 operations from December 1988 to December 2003. Graft and patient survival rates in eligible cases were computed with Kaplan-Meier analysis. Recipients were 808 men, 392 women of mean age 33.6 +/- 12.5 years. Eighty six percent of cases used organs from living donors (40% related, 41% unrelated, and 5% spouses) and 14% from cadaveric source. The most common causes of end-stage renal disease were chronic glomerulonephritis (18.2%); reflux nephropathy (13.4%); and diabetic nephropathy (10.1%). Among 215 (17.9%) patients, 156 patients (13%) died in the posttransplant period. Most common causes of death were cardiovascular (28.3%), graft loss (20.7%), and infections (19.6%). The 1- and 3-year patient survival rates were 94% and 91.5%, and graft survival rates were 88% and 84%. Although the success rate of operations was not satisfactory at the beginning, the current data reflect a >90% survival rate comparable to the major centers in the world.

Incidence of posttransplantation diabetes mellitus in kidney transplantation: a single-center experience.

Posttransplantation diabetes mellitus (PTDM) is a well-recognized complication of renal transplantation. PTDM is reported to contribute to major infections and cardiovascular complications and leads to increased posttransplantation morbidity. The present study was conducted to evaluate the frequency of PTDM in our center, to identify the role of immunosuppressive therapy and other risk factors in the genesis of PTDM, and to assess the impact of PTDM on graft and patient survival. From December 1998 to December 2003 we followed-up 1200 renal transplant recipients, including 121 recipients with pretransplantation diabetes mellitus and 1079 recipients without diabetes. PTDM occurred in 203 patients (mean age, 35.4 +/- 5.9 years); 131 (64.5%) were male. Graft loss and mortality were significantly higher in patients with PTDM versus those without. The overall reported incidence of PTDM worldwide varies from 3.4% to 46%. The incidence in our center is 18.8%. We also found a significantly higher incidence of PTDM among patients receiving grafts from living-related donors. This may be related to the higher cumulative doses of immunosuppressive drugs administered (in part, due to the greater number of acute rejections) in these patients.