Muramyl Tripeptide Plus Chemotherapy Reduces Metastasis in Non-Metastatic Osteosarcoma: A Single-Center Experience.

BACKGROUND: The immunomodulator mifamurtide plus a chemotherapy regimen has been shown to significantly improve the outcome in non-metastatic osteosarcoma patients. We report the results of the addition of mifamurtide to chemotherapy in newly diagnosed patients with osteosarcoma. METHODS: A total of 36 children with osteosarcoma without detectable metastasis were treated between November 2010 and April 2018 at the Ankara University Department of Pediatric Oncology. Mifamurtide was added to the chemotherapy regimen in 17 patients while the remaining 19 did not receive mifamurtide. The probabilities of metastasis and overall survival were compared between the groups. RESULTS: The 43-month survival rate was 87.5% and 89.9% in the patients who received and did not receive mifamurtide, respectively (p=0.65). Common side effects of mifamurtide were chills and fever. The addition of mifamurtide in the high-risk group with ≤95% necrosis tended to decrease the probability of distant metastasis (36.4% vs. 58.3%) (p=0.39). The time to metastasis in the group with positive surgical margins (4 months in one patient in the non-mifamurtide group, 7 and 20 months in the mifamurtide group) was also longer in the mifamurtide group. During the 43-month follow up period, median time to metastasis was longer in the mifamurtide group (20 vs. 5 months). In addition, mifamurtide plus chemotherapy decreased the risk of metastasis in the cases with primary site relapse. CONCLUSIONS: The addition of mifamurtide to chemotherapy might improve event-free survival by decreasing the probability of distant metastasis in bad histologic responders, and also by increasing the time to distant metastasis in the surgical margin positive group. Additional clinical studies are necessary to determine the long-term effects of mifamurtide on metastatic disease.
.

A novel graft option after pterygium excision: platelet-rich fibrin for conjunctivoplasty.

PurposeTo compare the surgical results, complications, and recurrence rates of primary pterygium excision with conjunctival autografts (CA) vs platelet-rich fibrin (PRF) grafts.Patients and methodsA total of 35 eyes of 35 patients with primary pterygium were included in the study. The patients underwent excision of pterygium followed by closure of the bare sclera by CA (group 1, n=20) vs PRF grafts (group 2, n=15). The PRF was generated from the patients' own whole-blood sample by centrifugation and pressing. The surgery times, intra/postoperative complications, recurrence rates of pterygium, and changes in visual acuity (VA) were evaluated and compared within groups.ResultsThe mean follow-up period was 14.3±6.5 months (6-24 months). The mean preoperative and postoperative VAs were same (20/25) (P=0.204). The mean surgery time was shorter in group 2 (22.1±1.9 min) compared to group 1 (33.8±7.8 min) (P=0.001). The recurrence was observed only in one (6.6%) case of group 2, while none of the cases showed recurrence in group 1. Graft loss was observed in 2 (10%) cases in group 1, and 1 (6.6%) case in group 2. No other intra/postoperative complications such as tear in the graft, excessive bleeding, scleral necrosis, graft necrosis, pannus formation, or symblepharon occurred in both groups.ConclusionsThis preliminary study showed encouraging results of the application of PRF for conjuntivoplasty after pterygium excision. The use of PRF in pterygium surgery is a simple, easily applicable, and a promising method with low rates of recurrence and complications.

Prognostic utility of serum vitronectin levels in acute myocardial infarction.

BACKGROUND: Vitronectin (VN) functions as a regulator of platelet adhesion and aggregation, coagulation, and fibrinolysis. The aim of this study was to assess the prognostic significance of serum VN levels in patients with acute myocardial infarction (MI). METHODS: In this study 62 patients admitted with ST-elevation myocardial infarction (STEMI), or non-ST-elevation myocardial infarction (NSTEMI) were enrolled. Serum VN levels were measured within 6 h after onset of chest pains. RESULTS: The VN serum levels were higher in MI patients with a mean of 2.257 µg/ml (range 1.541-4.493 µg/ml) in the STEMI group, 1.785 µg/ml (range 1.372-4.113 µg/ml) in the NSTEMI group, and 1.222 µg/ml (range 1.033-1.466 µg/ml) in the controls (p = 0.012). Major adverse cardiovascular events could be predicted at 6 months using VN levels independently of other variables [odds ratio (OR) 9.87, 95 % confidence interval (CI) 2.54-47.37, p = 0.001]. There was a significant positive correlation between VN levels and the Gensini score in NSTEMI patients (r = 0.436, p = 0.013). CONCLUSION: The VN level may be relevant as a clinical biomarker for adverse cardiovascular outcomes not only in patients with ischemic heart disease undergoing coronary interventions, as previously reported, but also in coronary artery disease patients presenting with acute MI.

Serum total and high-density lipoprotein phospholipids: independent predictive value for cardiometabolic risk.

OBJECTIVE: Given that serum phospholipids (PL) may serve as inflammation mediators, we studied whether they predicted metabolic syndrome (MetS), type-2 diabetes or coronary heart disease (CHD) risk in people prone to enhanced low-grade inflammation. METHODS: We analyzed unselected middle-aged Turkish adults with available serum total (n = 852) and HDL-PL (n = 428) measurements and follow-up (mean 6.6 years) by Cox or logistic regression, after exclusion of prevalent cases of outcome disorder. The enzymatic method used measured total content of phosphatidylcholine, sphingomyelin and lyso-phosphatidylcholine. RESULTS: Most lipid and non-lipid variables were significantly different in the upper two compared with the lowest total PL tertile, whereby apolipoprotein (apo)A-I and HDL-cholesterol were higher (not lower). ApoA-I, HDL-cholesterol and uric acid were uniformly positive independent linear covariates of total and HDL PL, apoA-I even in participants without MetS. After adjustment for sex, age, waist circumference, HDL-cholesterol and systolic blood pressure, logistic regression for incident MetS disclosed a 3-fold risk (RR [95% CI 1.28; 6.81]) in the upper HDL-pl tertile. In Cox regression models, while the combined two higher HDL-pl tertiles significantly protected against CHD risk in males (HR 0.29 [95% CI 0.10; 0.89]), they weakly tended to impart risk in females: upper two total PL tertiles tended to increased risk of diabetes and CHD. CONCLUSION: Excess total PL may mediate inflammatory properties to apoA-I, HDL and uric acid. Excess HDL-pl independently predict risk for MetS in each gender, but are protective against CHD risk in men, possibly because oxidized PL content mediated by total PL is sex-dependent, as reviewed elsewhere.

Impaired fasting glucose: Pro-diabetic, "atheroprotective" and modified by metabolic syndrome.

AIM: To investigate whether impaired fasting glucose (IFG) confers cardiovascular risk. METHODS: A non-diabetic population-based sample representative of middle-aged and elderly Turks was studied at 8.5 years' follow-up for incident diabetes and coronary heart disease (CHD). Metabolic syndrome (MetS) was defined by ATP-III criteria modified for male abdominal obesity, and IFG and type 2 diabetes were identified by criteria of the American Diabetes Association. Stratification by presence of MetS was used. Outcomes were predicted providing estimates for hazard ratio (HR) obtained by use of Cox proportional hazards regression analysis in models that controlled for potential confounders. RESULTS: In 3181 adults (aged 52 ± 11.5 years at baseline), analysis stratified by MetS, gender and IFG status distinguished normoglycemic subjects by a "hypertriglyceridemic waist" phenotype consisting of significantly higher waist circumference, fasting triglyceride and lower high-density lipoprotein-cholesterol, regardless of gender and MetS. Additionally, lipoprotein (Lp) (a) tended to be lower in (especially female) participants with MetS. Multivariable linear regression in a subset of the sample demonstrated decreased Lp (a) levels to be associated with increased fasting glucose and insulin concentrations, again particularly in women. In Cox regression analysis, compared with normoglycemia, baseline IFG adjusted for major confounders significantly predicted incident diabetes at a 3-fold HR in men and only women with MetS. Cox models for developing CHD in 339 individuals, adjusted for conventional risk factors, revealed that IFG status protected against CHD risk [HR = 0.37 (95%CI: 0.14-0.998)] in subjects free of MetS, a protection that attenuated partly in male and fully in female participants with MetS. CONCLUSION: IFG status in non-diabetic people without MetS displays reduced future CHD risk, yet is modulated by MetS, likely due to autoimmune activation linked to serum Lp (a).

[Turkish Adult Risk Factor Study survey 2012: overall and coronary mortality and trends in the prevalence of metabolic syndrome]. / TEKHARF 2012: Genel ve koroner mortalite ile metabolik sendrom prevalansi egilimleri.

OBJECTIVES: We aimed to analyze 1) overall and coronary mortality findings in the Turkish Adult Risk Factor (TARF) study survey 2012 and 2) the temporal trends in prevalence of metabolic syndrome (MetS) and its distribution across seven geographic regions. STUDY DESIGN: Information on the mode of death was obtained from first-degree relatives and/or health personnel of a local health office. Information collected in survivors was based on history, physical examination of the cardiovascular system and Minnesota coding of resting electrocardiograms. RESULTS: Of 1527 participants to be surveyed, 796 were examined; information was obtained on the health status in 502 subjects, and death was ascertained in 56 participants. Thirty deaths were attributed to coronary and cerebrovascular disease. Cumulative 22-year evaluation of participants in the age bracket 45-74 years revealed coronary mortality to be high, with 7.6 per 1000 person-years in men and 3.8 in women. Data used from 1754 identical subjects (median age 46 years initially), and examined in two periods 12 years apart, indicated an increase in the prevalence of MetS by 1.3% per aging of 1 year. Analysis across geographic regions showed a rise in the prevalence in the Mediterranean region, already having highest prevalence along with Southeast Anatolia, while the prevalence declined in the Marmara region and persisted to be lowest in the Aegean region. CONCLUSION: The prevalence of MetS in Turkish adults aged 40 years or over, currently standing at 53%, shows significant differences across geographic regions, being highest in the two southern regions and lowest in the Aegean region.

Heparin treatment for allergic conjunctivitis in the experimental BALB/c model.

PURPOSE: To compare the inhibitory effects of dexamethasone and heparin on the infiltration of mast cells in the conjunctiva by using a mouse allergic conjunctivitis model. METHODS: 24 Balb/c mice were divided into four groups: allergy group (positive control), dexamethasone group, heparin group, and negative control group, as groups 1, 2, 3, and 4, respectively. Each group comprised 6 mice, and experimental allergic conjunctivitis was developed in groups 1, 2, and 3. The mice in group 2 were treated with topical 0.1% dexamethasone eye ointment, and the mice in group 3 were treated topically with 5,000 IU/ml standard heparin. Both dexamethasone and heparin were instilled once a day for 4 days. Hanks' balanced salt solution was dropped into both eyes of the mice in group 4 instead of dexamethasone or heparin. Eyeballs and eyelids were removed from the mice in all groups while one eye of each animal was used for histopathological, the other for molecular biological examination. RESULTS: Mast cells, infiltrating the subconjunctival tissue, were significantly lower in group 2 (p < 0.0001), group 3 (p < 0.0001) and group 4 (p < 0.0001) when compared to group 1. CONCLUSIONS: Topical heparin could be a viable option in treating IgE-induced allergic eye disease since it is found to be as effective as topical dexamethasone in experimental acute allergic eye disease.

High rate of allergies among women with endometriosis.

Women with endometriosis frequently suffer from autoimmune inflammatory diseases, allergies and asthma. This study was conducted to examine whether the prevalence of allergies is higher in patients with endometriosis than in the control group, and to show potential correlation with endometriosis stages. We evaluated the medical files of 501 women with laparoscopically-diagnosed endometriosis and 188 women without endometriosis enrolled in Yale University Hospital. Main outcome measures used were allergy on medications, complaints of sinus or perennial allergic rhinitis, asthma, family history of allergic disease, and correlation with stages of endometriosis. Our results indicated that the overall risk of women with endometriosis and positive history of allergies was 4.28 (95% CI, 2.9-6.3) (p < 0.001). Significant excesses were identified for medications, sinus allergic rhinitis, and asthma; also, women with endometriosis were significantly more likely to report a positive family history of allergies. Overall, our study indicated a link between endometriosis and increased risk of allergic autoimmune disorders that should further be explored.

Postoperative changes related to intraoperative blood transfusions.

OBJECTIVE: Wound infection, flap necrosis rates and peripheral complete blood cell count changes related to intraoperative whole-blood transfusions were investigated. BACKGROUND: Evidence is growing that whole-blood cell transfusions are immunosuppressive and predispose patients to postoperative infections. METHODS: 102 female breast carcinoma patients with hemoglobin levels = 10 g/dl before modified radical mastectomy and < 10 g/dl intraoperatively but with no signs of oxygen debt were included. Group I included patients who had received two units of whole-blood transfusions intraoperatively. Patients who had received no transfusion were in group II. Peripheral complete blood cell count, wound infection rates and flap necrosis were compared. RESULTS: Perioperative neutrophile and monocyte count increased in both groups. This increase was especially significant in the transfused group (p < 0.05). In both groups, these changes returned to normal levels on the tenth postoperative day. The decreased perioperative basophile count did not return to the baseline even on the tenth postoperative day in group I (p < 0.05). Lymphocyte count, and flap necrosis did not differ between the groups (p > 0.05). Wound infection seemed to take place and increase in the transfused group (p < 0.05). CONCLUSION: Two units of whole-blood transfusions seem to increase wound infection and decrease basophile count in this series (Tab. 3, Ref. 30).

Endometriosis-associated Lyme disease.

The aim of this study is to report three cases of patients with endometriosis and infertility, and associated with Lyme disease. The medical files of 405 women with endometriosis and 200 without endometriosis were studied retrospectively. We report 3 cases with endometriosis and Lyme disease. Of 405 patients with endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme disease. All cases presented with typical erythema migraines, fever and fatigue. The serological findings were positive for Borrelia burgdorferi, for 3 cases. Two out of 3 women underwent IVF-ET procedures and one of them conceived in the first cycle without complication during pregnancy or after childbirth recorded. We concluded that women with endometriosis are more likely to have chronic fatigue syndrome, systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, multiple sclerosis, and other autoimmune inflammatory and endocrine diseases. A review of the literature confirms the uniqueness of the co-existence of Lyme disease in women with endometriosis in these cases.

Association of endometriosis with family history of non-Hodgkin's lymphoma: presentation of 10 cases.

PURPOSE: Women with endometriosis have been reported to be at increased risk of developing non-Hodgkin's lymphoma (NHL). The purpose of this article was to investigate the familial risk of NHL in women with endometriosis. We report on 10 cases with endometriosis and positive family history of NHL. METHODS: The medical records of 405 women with endometriosis and 200 without endometriosis were retrospectively analysed. All of the cases were diagnosed by laparoscopy. Ten cases of endometriosis having first-degree relatives with NHL are reported. RESULTS: We found no case with endometriosis and NHL. In contrast, we found 10/405 (2.5%) women with endometriosis and first-degree relatives with NHL. Their mean age was 38.3 years (range 29-46). The main complaint was infertility. The mean age at onset of endometriosis was 32 years (range 22-43). The stages of endometriosis were: stage II (n=4), stage III (n=2) and stage IV (n=4). All of these patients had first-degree relatives with a history of NHL. Five had mothers with NHL, 5 had fathers and one had a sister. CONCLUSION: These cases could suggest a link between a family history of NHL and subsequent development of endometriosis in the first-generation women. Moreover, there was no evidence of association between endometriosis and NHL.

Epidemiological factors influencing IVF outcome: Evidence from the Yale IVF program.

Age, BMI, lifestyle, menstrual status and obstetric history can modulate the endocrine system and, therefore, have been hypothesised to play a role in in-vitro fertilisation (IVF) outcome. We designed a retrospective study, set in a medical school hospital. We evaluated the medical files of 297 infertile women who underwent laparoscopy and consecutive IVF-ET treatment in the Yale IVF unit between 1996 and 2002. The study group consisted of 151 women who conceived after IVF-ET and the control group of 146 women who underwent 288 IVF-ET cycles without pregnancy. The main outcome measure was the impact of epidemiological factors on the IVF outcome. There was no association between IVF outcome and race, BMI, age at menarche, length of cycle, duration and amount of flow, menstrual symptoms, other medical problems, medical history of allergies, and family history of endometriosis and cancer. We found that the degree of smoking and alcohol use was not a factor when comparing women with and without pregnancy after IVF (34.5% vs 29.5%, and 33.7% vs 27%, respectively). The rate of duration of infertility tended to be lower in pregnant women (35.9+/-23.4 months) vs (42.3+/-30.2) non-pregnant women. As expected, we also confirmed the inverse association between the age of women and IVF outcome. Overall, body attributes, lifestyle, family history, menstrual and reproductive factors were not related to IVF-ET outcome.

Effects of topical dorzolamide on IOP after phacoemulsification with different types of ophthalmic viscosurgical devices.

PURPOSE: To evaluate the effect of topical dorzolamide on postoperative intraocular pressure (IOP) after routine phacoemulsification surgery with different type of ophthalmic viscosurgical device (OVD). METHODS: Patients who were scheduled for phacoemulsification with intraocular lens (IOL) implantation were evenly divided into four groups. Group I (83 eyes) received one drop of topical dorzolamide immediately after surgery and 1.4% NaHa (BD Visc) was used as a cohesive OVD during IOL implantation. Group II (83 eyes) did not receive any topical antiglaucoma medication after operation and 1.4% NaHa was used as a cohesive OVD. Group III (83 eyes) received topical dorzolamide and 1% NaHa (Healon) was used, and Group IV (83 eyes) did not receive any topical and 1% NaHa was used in operation. Mean postoperative IOPs were compared between groups. RESULTS: Eyes with 1.4% NaHa usage (18.2+/-9.2 mmHg) had higher mean postoperative IOPs than eyes with 1% NaHa usage (15.5+/-5.3 mmHg) (p=0.002). Mean postoperative IOPs were lower in eyes with dorzolamide application (15.6+/-7.2 mmHg) than in eyes without any medication (18.1+/-8.5 mmHg) both in eyes with 1.4% NaHa and 1% NaHa usage (p=0.003). Dorzolamide application caused an average 2.5 mm decrease in mean postoperative IOPs in both groups. CONCLUSIONS: Effects of OVDs on IOP rises after phacoemulsification surgery are closely related to their molecular structure. Increase in viscosity rendered higher postoperative IOP increments. However, topical dorzolamide application effectively reduced postoperative IOP increments in eyes with both Healon and BD Visc use.

Common adiponectin gene variants show different effects on risk of cardiovascular disease and type 2 diabetes in European subjects.

Alterations in the secretion of adipokines may explain the link between obesity, type 2 diabetes (T2DM) and coronary artery disease (CAD). These conditions have been associated with variation in the adiponectin gene, although evidence for this relationship has been variable, with differences found even in similar samples. This study aims to clarify these inconsistencies by determining the impact of identified adiponectin gene (ADIPOQ) variants (-11391G>A,-1377C>G[promoter] and +45T>G[exon 2] and +276G>T[intron 2]) on the prospective risk of CAD and T2DM in healthy men, and on adverse metabolic markers, in myocardial infarct survivors and controls from different parts of Europe. The hazard ratio for cardiovascular disease varied across the -11391GG/GA/AA(p = 0.03) and -11371CC/CG/GG(p = 0.05) genotypes only. In contrast, only the +45T>G variant (3.80[1.76-8.24]) was associated with T2DM, while two haplotypes GCTT/GCGG (p < 0.05) and +276G>T(p = 0.01) increased risk in interaction with obesity. The variants were associated with a number of biomarkers in Southern but not Northern Europe (p = 0.01), despite no significant differences in allele or haplotype frequencies (p > 0.44). A risk haplotype could not be identified in either sample. Adiponectin gene variants are hence currently poor markers for the development of T2DM and CAD. Their influence on risk depends significantly on interactions that are not currently understood with either genetic variation elsewhere or the environment of the sample studied.

VSOne, a virtual reality simulator for laparoscopic surgery.

The introduction of computer-based training systems for laparoscopic surgery has increased the training quality and made the learning effect measurable with objective criteria. This paper introduces VSOne as a fully-featured virtual reality training system for laparoscopic surgery. VSOne utilizes the state-of-the-art in virtual reality techniques, soft tissue simulation and haptic device control and guarantees realistic training possibilities for various laparoscopic procedures. An authoring software helps to create individual simulation models easily within the shortest time based on real patient data using standardized data formats. We have developed several Basic Task Training (BTT) modules to improve dexterity and complex Surgical Procedure Task (SPT) modules for full training of laparoscopic procedures such as cholecystectomy, tubal sterilization and myomectomy. VSOne has been evaluated in a comparative study with classic training methods and has shown the typical learning curves for inexperienced trainees and the transferability of the learning effect to the real-world situation.

The medical engineering program of Forschungszentrum Karlsruhe.

The research activities of the Forschungszentrum Karlsruhe on minimally-invasive surgery (MIS) have for several years improved techniques and instrumentation for different types of MIS. Many types of instruments and robotic devices have been developed and new techniques implemented. In this paper we present the most recent results from our different projects, such as endoscopic heart surgery, tracking systems, a camera guidance device, telemanipulator systems, minimally-invasive breast biopsy in closed-bore MRI, endoscopic training simulators and developments using smart materials (e.g. Nitinol).