Relationship between anti-Müllerian hormone and antral follicle count across the menstrual cycle using the Beckman Coulter Access assay in comparison with Gen II manual assay.

BACKGROUND: The study aim was to validate Beckman Coulter's fully automated Access Immunoassay System (BC Access assay) for anti-Müllerian hormone (AMH) and compare it with Beckman Coulter's Modified Manual Generation II assay (BC Mod Gen II), with regard to cycle AMH fluctuations and antral follicle counts. METHODS: During one complete menstrual cycle, transvaginal ultrasound was performed on regularly menstruating women (n=39; 18-40years) every 2 days until the dominant ovarian follicle reached 16mm, then daily until observed ovulation; blood samples were collected throughout the cycle. Number and size of antral follicles was determined and AMH levels measured using both assays. RESULTS: AMH levels measured by the BC Access assay vary over ovulatory menstrual cycles, with a statistically significant pre-ovulatory decrease from -5 to +2 days around objective ovulation. Mean luteal AMH levels were significantly lower (-7.99%) than mean follicular levels but increased again towards the end of the luteal phase. Antral follicle count can be estimated from AMH (ng/mL, BC Access assay) concentrations on any follicular phase day. BC Access assay-obtained AMH values are considerably lower compared with the BC Mod Gen II assay (-19% on average); conversion equation: AMH BC Access (ng/mL)=0.85 [AMH BC Mod Gen II (ng/mL)]0.95. CONCLUSIONS: AMH levels vary throughout the cycle, independently of assay utilised. A formula can be used to convert BC Access assay-obtained AMH levels to BC Mod Gen II values. The number of antral follicles can be consistently estimated from pre-ovulatory AMH levels using either assay.

Prognostic value of the new high sensitive cardiac troponin T assay (hs-cTnT) after coronary artery bypass grafting.

Background The aim of the study was to assess the value of post-operative cardiac troponin T-levels, measured with a new highly sensitive assay (hs-cTnT), as a suitable parameter to predict patients' outcome after cardiac surgery. With the introduction of the new hs-cTnT assay the correlation between measured levels and the post-operative patient's outcome remains to be evaluated. Methods Patients undergoing coronary artery bypass grafting (n = 213) were included. Perioperative measurements of hs-cTnT and CK-MB were correlated to parameters of clinical outcome and further explored. Patients with an uneventful course were compared with those with post-operative complications, including need of repeat revascularization (RR) or death (RR/death), cardiogenic shock (CS) or death (CS/death) and a combination of all (RR/CS/death). Results Significant results were observed in patients after isolated CABG, where CS/death and RR/CS/death patients had higher post-operative hs-cTnT levels (P < 0.01). Moreover, multivariate analysis of the CABG-group revealed that acute renal failure (OR =14.7, 95% CI =2.7-79.1, P < 0.001), early post-operative hs-cTnT levels higher than the upper quintile (> 1,476.8 pg/ml) (OR =8.1, 95% CI =3.0-22.2, P < 0.001) and unstable angina pectoris (OR =2.4, 95% CI =1.1-5.7, P < 0.05) were the most powerful independent predictors of post-operative complications. Upon discriminant analysis the application of hs-cTnT almost doubled the sensitivity of the outcome prediction. Conclusions The new hs-cTnT assay is a useful diagnostic tool that may significantly enhance the prediction of adverse events after CABG. In our study a hs-cTnT-value >1,476.8 pg/ml proved to be a reliable marker for ongoing post-operative complications.

Determinants of cumulative ART live-birth rates in a single-center study: age, fertilization modality, and first-cycle outcome.

PURPOSE: To analyze cumulative and single-cycle success rates of IVF and intracytoplasmic sperm injection (ICSI) separately in relation to female age, fertilization modality, and first-cycle outcome. METHODS: The study involved 2997 patients and couples, respectively, who underwent 5339 fresh and 3006 cryo cycles using pronuclear-stage oocytes. Fertilization was achieved by the conventional IVF or ICSI. Because of legal restrictions in Germany, no embryo selection was performed. All cycles were documented prospectively. Kaplan-Meier survival rates were calculated for all treatment cycles and transferred embryos. RESULTS: Essentially, the success of assisted reproductive technology (ART) depends on a woman's age and on skilful counselling. Cumulative pregnancy and live-birth rates are the best indicators of successful ART. Probably for the first time, we determined these cumulative rates separately for IVF and ICSI, and found them to be almost identical. Live-birth rates reached 70-95 %, except for women aged over 40 years, whose chances of life birth are limited to about 25 %. Live-birth rate per retrieval was 25.61 % for IVF and 26.3 % for ICSI. Time to pregnancy was shorter for women who underwent a successful treatment in their first cycle. CONCLUSIONS: The primary intention for the choice of fertilization modality between IVF and ICSI is the prevention of a relative or total fertilization failure. Such treatment failure is best prevented through ICSI, which results in slightly higher clinical pregnancy rates per started cycle. After embryo transfer, there are no differences in the success rates of IVF and ICSI. The supposed cumulative live-birth rates are useful as a basis for counselling subfertile couples to help reduce the high discontinuation rate, which is still the main reason for inefficacy in ART. Following an unsuccessful first treatment cycle, the prognosis remains positive, but until success is achieved, more treatment cycles are necessary.

Intermittent Cold-Blood Cardioplegia and Its Impact on Myocardial Acidosis during Coronary Bypass Surgery.

BACKGROUND: The purpose of the study was to assess the degree of myocardial acidosis in patients undergoing elective coronary bypass surgery, in whom intermittent cold-blood cardioplegia (ICBC) was used for myocardial protection. The results of this study are presented in comparison to those of a previous trial conducted by the same investigators, using a similar methodology, but with intermittent warm-blood cardioplegia (IWBC). PATIENTS AND METHODS: In 15 patients undergoing elective myocardial revascularization with ICBC for myocardial protection, metabolic changes of global ischemia indicators, lactate and pH values (measured simultaneously in coronary sinus and arterial blood) were analyzed. Lactate concentrations and pH values were measured at the beginning and the end of each cardioplegia administration, and the change-overtime analysis of the values was performed. For comparison with the results of the previous study (IWBC method) consisting of 12 patients, the analysis of variance with repeated measurements, including tests for a crossover, group, and time effect were used. RESULTS: Using the ICBC method, as compared with IWBC, no significant difference in the lactate production was observed during the first two successive cardioplegia administrations. During the third and fourth administrations, especially at the end of reperfusions, ICBC patients had a significantly lower lactate release and higher pH values, as compared with IWBC patients. CONCLUSION: Our results suggest that ICBC has an inhibiting effect on potentially progressive myocardial acidosis during cross-clamp period.

Impact of sperm cell source on the results of intracytoplasmic sperm injection.

PURPOSE: There is an ongoing debate whether the source of sperm cells, the etiology or the extent of male factor infertility has influence on the outcome of ICSI cycles. METHODS: The results of intracytoplasmic sperm injection (ICSI) according to the source of spermatozoa in patients with severe male factor infertility were compared in a retrospective study: 249 couples underwent a total of 337 fresh ICSI cycles with the use of fresh motile testicular or fresh motile ejaculated spermatozoa. RESULTS: For all variables, there were no statistically significant differences in the ICSI results between both groups. Fertilization rates were 46.8% for testicular and 47.6% for ejaculated spermatozoa. Live birth rates per embryo transfer were 20.4% using testicular spermatozoa and 22.8% using ejaculated spermatozoa. CONCLUSIONS: Neither the source of spermatozoa nor the etiology of severe male infertility has relevant impact on the results of ICSI cycles as long as fresh motile, morphologically normal spermatozoa are used. Therefore, in case of cryptozoospermia, we recommend to preferentially use ejaculated spermatozoa to prevent those men from an unnecessary testicular biopsy avoiding risks and costs implied.

Monitoring the menstrual cycle: Comparison of urinary and serum reproductive hormones referenced to true ovulation.

OBJECTIVE: The aim of the study was to examine relationships and interindividual variations in urinary and serum reproductive hormone levels relative to ultrasound-observed ovulation in menstrual cycles of apparently normally menstruating women. METHODS: This was a prospective study of normally menstruating women (no known subfertility), aged 18-40 years (n = 40), who collected daily urine samples and attended the study centre for blood samples and transvaginal ultrasound during one complete menstrual cycle. Serum luteinising hormone (LH), progesterone, estradiol, urinary LH, pregnanediol-3- glucuronide (P3G) and estrone-3-glucuronide were measured. Ultrasound was conducted by two physicians and interpreted by central expert review. RESULTS: Menstrual cycle length varied from 22 to 37 days (median 27 days). Ovulation by ultrasound ranged from day 8 to day 26 (median day 15). Serum and urinary hormone profiles showed excellent agreement. Estrogen and LH hormone peaks in urine and serum showed a range of signal characteristics across the study group before and after ovulation. The rise in estrogen and LH always occurred before ovulation; the progesterone rise from baseline always occurred after ovulation. CONCLUSIONS: Urinary and serum reproductive hormones showed excellent agreement and may be used interchangeably. The beginning of the surge in serum and urinary LH was an excellent predictor of ovulation. The rise in progesterone and P3G above baseline was a consistent marker of luteinisation confirming ovulation. Both LH and progesterone surges delivered clear, sharp signals in all volunteers, allowing reliable detection and confirmation of ovulation.

Prospective evaluation of magnetic resonance imaging guided in-bore prostate biopsy versus systematic transrectal ultrasound guided prostate biopsy in biopsy naïve men with elevated prostate specific antigen.

PURPOSE: Magnetic resonance imaging guided biopsy is increasingly performed to diagnose prostate cancer. However, there is a lack of well controlled, prospective trials to support this treatment method. We prospectively compared magnetic resonance imaging guided in-bore biopsy with standard systematic transrectal ultrasound guided biopsy in biopsy naïve men with increased prostate specific antigen. MATERIALS AND METHODS: We performed a prospective study in 132 biopsy naïve men with increased prostate specific antigen (greater than 4 ng/ml). After 3 Tesla functional multiparametric magnetic resonance imaging patients were referred for magnetic resonance imaging guided in-bore biopsy of prostate lesions (maximum 3) followed by standard systematic transrectal ultrasound guided biopsy (12 cores). We analyzed the detection rates of prostate cancer and significant prostate cancer (greater than 5 mm total cancer length or any Gleason pattern greater than 3). RESULTS: A total of 128 patients with a mean ± SD age of 66.1 ± 8.1 years met all study requirements. Median prostate specific antigen was 6.7 ng/ml (IQR 5.1-9.0). Transrectal ultrasound and magnetic resonance imaging guided biopsies provided the same 53.1% detection rate, including 79.4% and 85.3%, respectively, for significant prostate cancer. Magnetic resonance imaging and transrectal ultrasound guided biopsies missed 7.8% and 9.4% of clinically significant prostate cancers, respectively. Magnetic resonance imaging biopsy required significantly fewer cores and revealed a higher percent of cancer involvement per biopsy core (each p <0.01). Combining the 2 methods provided a 60.9% detection rate with an 82.1% rate for significant prostate cancer. CONCLUSIONS: Magnetic resonance imaging guided in-bore and systematic transrectal ultrasound guided biopsies achieved equally high detection rates in biopsy naïve patients with increased prostate specific antigen. Magnetic resonance imaging guided in-bore biopsies required significantly fewer cores and revealed a significantly higher percent of cancer involvement per biopsy core.

Survival predictors in ventricular assist device patients with prior extracorporeal life support: selecting appropriate candidates.

Several centers turn patients down for long-term ventricular assist devices (VADs) once they have received extracorporeal life support (ECLS) due to the expected poor outcome in these patients. The aim of this study was to identify survival predictors in this cohort of patients. Data of patients undergoing VAD support between January 2010 and November 2013 were retrospectively reviewed. Patients on ECLS support before implantation were considered eligible for inclusion. Outcome in survivors following long-term VAD support was compared with outcomes in nonsurvivors. Student's t-test and χ(2)-test were used as applicable. A total of 65 long-term VADs were implanted. The inclusion criteria were met by 24 patients. Eight patients did not survive the first 30 days. All preoperative characteristics were comparable between the two groups except for statistically higher Model for End-stage Liver Disease (MELD) score, bilirubin, white blood cell count, and blood urea nitrogen in nonsurvivors (P = 0.002, 0.01, 0.01, and 0.003, respectively). Stepwise discriminant analysis revealed MELD score as the most important survival predictor. Based on this analysis, an outcome predictor formula was generated. The 30-day and 1-year survival rates were 67% and 54%, respectively. In this study, we were able to determine survival predictors in VAD patients with prior ECLS support. The outcome in these patients is limited and associated with higher postoperative complications, particularly right ventricular and respiratory failure. The pre-VAD MELD score is an important predictor of poor outcome.

Time is brain?--Surgical revascularization of acute symptomatic occlusion of the internal carotid artery up to one week.

BACKGROUND: Clinical outcome and surgical success rate of open surgical reconstruction for acute symptomatic internal carotid artery (ICA) occlusion up to 1 week after stroke onset were analyzed to determine a cutoff time, after which risk exceeds clinical benefit. METHODS: From November 1997 to March 2007, a total of 5369 patients were examined at the authors' stroke unit; 502 from this cohort underwent ICA reconstruction. A subgroup of 49 patients underwent surgical revascularization of acute ICA occlusion within 168 hr at a mean of 42.5±38.7 hr after stroke onset. Preoperative diagnostic measures consisted of extracranial/intracranial duplex sonography (n=49), cerebral computed tomography (n=31), magnetic resonance imaging and angiography (n=37), and digital subtraction angiography (n=24). All 49 patients experienced a complete ICA occlusion and an ipsilateral recent ischemic infarction. Modified Rankin scale score (mRS) before surgery was 0 to 3 in 20 patients (41%) and 4 to 5 in 29 patients (49%). RESULTS: ICA patency could be restored in 38 patients (78%). The following clinical outcomes were noted: clinical improvement in mRS by at least 1 point in 23 of 49 of patients (47%), no change in 14 of 49 (28%), deterioration in mRS by at least 1 point in 6 of 49 (12%), and death within 30 days in 6 of 49 (12%). A total of 21 patients (43%) experienced perioperative cerebral events (new infarction, new intracranial hemorrhage or enlargement, or hemorrhagic transformation of the preexisting infarction). Univariate analysis showed that clinical improvement correlated significantly with success of recanalization and with early recanalization within 72 hr. Age, gender, and preoperative Rankin stage did not have influence. Clinical deterioration or death was only associated with perioperative cerebral events and seemed to be time-independent. Multivariate analysis did not have enough statistical power to analyze the impact of different risk factors on outcome after urgent revascularization. CONCLUSIONS: In patients who undergo surgery after 72 hr from symptom onset, the risk seems to outweigh the benefit.

Whole body MRI in type I Gaucher patients: evaluation of skeletal involvement.

BACKGROUND: Bone disease is a serious complication of type 1 Gaucher disease, which if untreated can result in pain, disability and reduced quality of life. MRI is the method of choice for assessing and monitoring bone involvement in Gaucher patients. MRI bone evaluation has been predominantly carried out on the lumbar spine and/or lower extremities using quantitative or semi-quantitative methods. We describe evaluation of skeletal involvement in Gaucher patients using whole body MRI scanning. METHODS: Whole body MRI was performed in 39 adult type I Gaucher patients using a 1.5 T superconducting magnet with total imaging matrix technology. A standard MRI protocol was performed in all patients using coronal T1-, T2-weighted (thighs) and STIR-sequences of the whole body, sagittal T1-, T2- (lumbar spine) and STIR-sequences of the entire axial skeleton. Bone marrow involvement was analysed using the Düsseldorf Gaucher score (DGS), bone marrow burden score (BMB), and vertebra-disc-ratio (VDR). Pelvis, humerus, legs and spine were also analysed using the pattern of marrow involvement described by homogeneous type A or non-homogeneous type B morphology. Avascular necrosis (AVN) of the humeral head was determined. RESULTS: Whole body MRI was well tolerated and of diagnostic value in all patients. Thirty one out of 39 patients (79%) showed bone involvement. In fifteen of these 31 patients (48%) humeral bone involvement was observed. The morphological appearance of bone involvement (type A or B) was consistent across the humerus, legs and pelvis. The infiltration pattern was also similar across cervical, thoracic and lumbar vertebral bodies. Humeral bone involvement was present in 89% of patients with type B morphology compared with 32% of patients with type A morphology (p<0.005). Humeral involvement was detected more frequently in patients with severe bone involvement as determined by higher DGS and BMB scores, than in patients with lower DGS and BMB scores (p<0.0001 and p=0.0016). AVN of the humeral head was detected in 6 patients (19%). CONCLUSIONS: In this group of patients, severe bone involvement in the lumbar spine and lower extremities and type B morphology was also associated with humeral involvement. The morphological infiltration pattern was consistent in the entire skeleton indicating the systemic character of bone disease. Whole body MRI presents a feasible means of assessing the entire skeletal system and could be a valuable diagnostic and monitoring tool in the management of patients with type 1 Gaucher disease.

Single-center experience with open surgical treatment of 36 infected aneurysms of the thoracic, thoracoabdominal, and abdominal aorta.

BACKGROUND: To describe a single-center experience with open surgical treatment of infected aortic aneurysms. We analyzed risk factors for 90-day mortality. METHODS: Between 1983 and 2008, 4,410 patients underwent open surgery for thoracic, thoracoabdominal, or abdominal aneurysm at our institution. Primary infection of the aneurysm was suspected because of clinical signs of infection in combination with typical radiological and morphological aspects in 66 patients (1.5%). In all, 36 patients displayed 10 different kinds of organisms in cultures of blood and/or intraoperative specimens and were further analyzed. RESULTS: The group consisted of 23 men and 13 women, with a mean age of 66.8 ± 8 (50-84) years. Location of the aneurysm was thoracic in five patients (14%), thoracoabdominal in 13 patients (36%), and abdominal in 18 patients (50%). Eleven patients (28%) were treated before and 25 (72%) after 1995. We found free rupture in three cases; contained rupture into surrounding tissue in 23 cases (64%); penetration into lung, bronchus, esophagus, or inferior vena cava in five cases; and an intact aneurysm in another five cases. Kinds of surgery were as follows: extra-anatomic revascularization in four patients (11%), Dacron patch plasty in four patients (11%), in situ revascularization in 24 patients (66%), and four patients died during surgery before reconstruction (11%). In all, 13 patients died during hospital stay (36%). In 25 patients treated after 1995, 90-day mortality was 24% and was significantly better (p < 0.05) than the rate of 64% in 11 patients treated before 1995. Outcome depended on status of rupture: all patients with free rupture, three of five patients (60%) with rupture into an organ, seven of 23 patients (30%) with contained rupture into the surrounding tissue, but no patient with intact aneurysm died. Age, gender, bacterium, location of the aneurysm, and method of surgical treatment did not influence 90-day mortality. During follow-up, 18 patients died after a mean of 56 ± 49 months. One patient died because of an infected aortic prosthesis. CONCLUSIONS: Outcome of patients with infected aortic aneurysms has improved during the last 15 years and depends on the status of rupture at time of surgery. Therefore, only early diagnosis and early treatment can further improve the prognosis.

Critical chronic peripheral arterial disease: does outcome justify crural or pedal bypass surgery in patients with advanced age or with comorbidities?

BACKGROUND: We wanted to know the effect of comorbidity, age, and gender on the outcome after surgical below-knee revascularization for critical chronic limb ischemia. METHODS: This is a retrospective study of 624 consecutive patients who underwent below-knee bypass surgery between January 1996 and December 2005 because of chronic peripheral arterial disease (PAD). Patients' characteristics were: diabetes mellitus (DM) n = 445 (71%), coronary artery disease (CAD) n = 310 (49%), dialysis-dependent renal insufficiency (dRI) n = 88 (14%), age >70 years n = 279 (44%), male n = 423 (68%), PAD Fontaine's stage III n = 105 (17%), and PAD stage 4 n =519 (83%). All patients had Trans Atlantic Inter-Society Consensus (TASC) C and D lesions, all were treated with a vein bypass to a crural artery n = 354 (57%) and to a pedal artery n = 270 (43%). Kaplan-Meier analysis and multivariate analysis were performed. RESULTS: The early results were as follows. The 30-day major amputation rate was n = 43 (7%). CAD, dRI, age, and gender did not influence major amputation rate, whereas patients with diabetes had a lower risk of early amputation than those without diabetes. (hazard ratio: 0.49, 95% confidence interval: 0.25-0.95, p < 0.05). The 30-day mortality rate was n = 31 (5%) and was uninfluenced by DM, CAD, and gender. Patients with dRI and octogenarians had a high risk of early death (dRI: 13.6%, octogenarians 9.4%). The late results were as follows. Follow-up rates were: limb salvage n = 596 (95.5%) and survival n = 622 (99.7%). The limb salvage rates at 1, 3, and 5 years were 79.1%, 72.1%, and 66.4%, respectively, and were uninfluenced by DM, CAD, dRI, age, and gender. The mortality rates at 1-, 3-, and 5-years were 79%, 63.4%, and 47.3%, respectively. Comorbidities such as CAD, dRI, and age of >70 years reduced life expectancy significantly. DM did not influence 1, 3 and 5 years of survival. The 5-year survival rates as estimated by Kaplan-Meier analysis after revascularization were: DM, 46%; CAD, 38%; dRI, 19%; and age >70 years, 37%. CONCLUSION: Advanced age and comorbidities reduce life span but not the chance of avoiding major amputation after below-knee bypass surgery for critical limb ischemia.

Does atovaquone prolong the disease-free interval of toxoplasmic retinochoroiditis?

BACKGROUND: To evaluate the efficacy of suppressing a recurrence of Toxoplasma retinochoroiditis after treatment with atovaquone. METHODS: Retrospective, nonrandomized, clinical trial. Forty-one immunocompetent patients were treated for Toxoplasma retinochoroiditis with atovaquone between 1999 and 2006. The diagnosis was based on clinical signs alone. Atovaquone was given 750 mg two to three times daily together with oral steroids. Lesion location, time interval until recurrence, visual function, and adverse events were recorded. RESULTS: Forty-two eyes of 41 patients were treated with atovaquone for Toxoplasma retinochoroiditis. Side-effects were usually mild and only one patient stopped therapy with atovaquone because of nausea. Reactivation of retinochoroiditis occurred in 18 patients (44%) during a time interval of 3-70 months. CONCLUSIONS: The therapy of Toxoplasma retinochoroiditis with atovaquone is well tolerated. Our data suggests that therapy with atovaquone has the potential to prolong the time to recurrence of Toxoplasma retinochoroiditis. A prospective randomized comparative long-term clinical trial would be necessary to confirm our data.

Prospective randomized trial of operative vs interventional treatment for renal artery ostial occlusive disease (RAOOD).

INTRODUCTION AND OBJECTIVES: Patients with either renovascular hypertension (RVH) and/or renal insufficiency (RI) due to renal artery ostial occlusive disease (RAOOD) can successfully undergo an open surgical reconstruction procedure (OSRP), but since the publication of Blum et al(1) percutaneous balloon stent angioplasty (PTRA + stent) leaving a small part of the stent within the aorta has become very popular. However, balloon dilatation and stenting does not remove the atherosclerotic plaque, which is often heavily calcified but leads to disruption of the plaque causing myointimal hyperplasia and recurrent stenosis. Therefore, a comparison of the two treatment modalities concerning complications and durability in a prospective randomized design was felt to bring more insight to the discussion. METHODS: From 1998 to 2004, we performed OSRP in 330 patients with RVH and/or RI for various locations of RAOOD. During this time period, 50 patients (female 18, male 32, mean age 64.4 years) with RAOOD of at least 70% stenosis (DSA and duplex criteria) in one or both renal arteries, who did not require other aorto/mesenteric/iliac reconstructive procedures agreed and were randomized to either OSRP (n = 25 patients, 49 arteries) or PTRA + stent (n = 25 patients, 28 arteries). Two patients crossed over to surgical treatment. Patients were followed on a regular basis for 4 years and longer. Endpoints were re-occurrence of RAOOD and impairment of either kidney function or RVH. RESULTS: We approached 77 arteries. There was no early mortality in either group, but directly procedure-related morbidity was 13% in the interventional group and 4% in the surgical group. Four-year follow-up mortality was 18% in the interventional group and 25% in the surgical group. Both groups showed significant improvement of RVH (P < .001 in each group) as well as improvement or stabilization in patients with insufficient renal function. Freedom from recurrent RAOOD (>70%) was achieved in 90.1% of the surgical group and 79.9% of the interventional group. CONCLUSION: Both treatment modalities showed good early results concerning RVH, kidney function, and renal perfusion. Despite a higher number of bilateral renal artery reconstructions in patients undergoing OSRP, which was probably due to the preferred technique of transaortic endarterectomy eliminating the plaque originating in the aorta and usually extending into both renal arteries, mortality was not higher and procedure-related morbidity was even lower compared to PTRA + stent. These findings and also longer durability of OSRP imply that surgical reconstruction remains the gold standard for patients with RAOOD before PTRA + stent may be considered.

Surgical decision making for revascularization of chronically occluded right coronary artery.

OBJECTIVE: Chronic totally occluded right coronary artery (CTO-RCA) often poses a problem in decision making for/against bypass grafting due to the lack of standardized indication criteria. The aim of the study was to investigate whether qualitative angiograms can be useful in decision making for/against surgical revascularization of CTO-RCA. METHODS: A retrospective cohort study was conducted with 69 patients who underwent elective CABG procedure, including single graft to the RCA. The distal run-off of the bypassed RCA was measured intraoperatively using the ultrasonic transit-time method. As a primary endpoint of the study, the flow values were analysed in regard to diameter of the recipient artery. As a secondary endpoint, the correlations between the regional and global LV function, Rentrop grading, type of collateral pathway, number of donor sources, comorbidity, and the graft flow and the diameter of the recipient artery were investigated using uni- and multi-variate regression analyses. RESULTS: In general, the flow values correlated significantly with the diameter of the recipient artery. Significantly lower flow (p < 0.0001) and diameter values (p < 0.05) were found in hypo/akinetic and infarcted area reflecting functionality of the CTO-RCA territory. CONCLUSIONS: The qualitative angiograms combined with regional wall motion studies can be useful in decision making for revascularization of CTO-RCA. Revascularization of akinetic/infarcted CTO-RCA territory is associated with lower graft flows even in patients presented with high Rentrop class and high degree of collaterality, suggesting necessity of viability tests prior to bypass surgery.

FTO Is Associated with Aortic Valve Stenosis in a Gender Specific Manner of Heterozygote Advantage: A Population-Based Case-Control Study.

BACKGROUND: Single nucleotide polymorphisms (SNPs) within the Fat mass and obesity associated (FTO) gene have been linked with increased body weight. However, the data on an association of FTO with cardiovascular diseases remains conflicting. Therefore, we ascertained whether FTO is associated with aortic valve stenosis (AVS), one of the most frequent cardiovascular diseases in the Western world. METHODS AND FINDINGS: In this population-based case-control study the FTO SNP rs9939609 was analyzed in 300 German patients with AVS and 429 German controls of the KORA survey S4, representing a random population. Blood samples were collected prior to aortic valve replacement in AVS cases and FTO rs9939609 was genotyped via ARMS-PCR. Genotype frequencies differed significantly between AVS cases and KORA controls (p = 0.004). Separate gender-analyses uncovered an association of FTO with AVS exclusively in males; homozygote carriers for the risk-allele (A) had a higher risk to develop AVS (p = 0.017, odds ratio (OR) 1.727; 95% confidence interval (CI) 1.087-2.747, recessive model), whereas heterozygote carriers for the risk-allele showed a lower risk (p = 0.002, OR 0.565, 95% CI 0.384-0.828, overdominant model). After adjustment for multiple co-variables, the odds ratios of heterozygotes remained significant for an association with AVS (p = 0.008, OR 0.565, 95% CI 0.369-0.861). CONCLUSIONS: This study revealed an association of FTO rs9939609 with AVS. Furthermore, this association was restricted to men, with heterozygotes having a significantly lower chance to develop AVS. Lastly, the association between FTO and AVS was independent of BMI and other variables such as diabetes mellitus.

Antimüllerian hormone levels and numbers and sizes of antral follicles in regularly menstruating women of reproductive age referenced to true ovulation day.

OBJECTIVE: To assess menstrual cycle antimüllerian hormone (AMH) levels in reproductive age women and which/how many follicles substantially produce AMH. DESIGN: Prospective study of menstruating women using mixed-effects models to analyze AMH variability and correlation of follicle counts/size classes to AMH levels. SETTING: Clinic. PATIENT(S): Regular menstruating women with ovulatory cycles (n = 40, aged 18-37 years) and no known subfertility. INTERVENTION(S): Women collected daily urine samples and visited the study center for blood samples/transvaginal ultrasound during one complete menstrual cycle (visits were every 2 days; daily from follicle size >16 mm until postovulation). MAIN OUTCOME MEASURE(S): AMH levels throughout the menstrual cycle, correlated with antral follicles as observed by ultrasound and identification of follicles producing AMH. RESULTS: Of all antral follicles visible by high-resolution ultrasound, AMH is produced substantially only by follicles up to 7 mm in diameter. For women with basal AMH >1 ng/mL, mean AMH concentrations vary across ovulatory menstrual cycles, showing a statistically significant decrease from -5 to 2 days after objective ovulation; significantly lower mean luteal AMH levels (-7.59% to mean follicular AMH) are detected. The number of antral follicles can be estimated from AMH (ng/mL) levels using the modified Beckman Coulter Generation II AMH assay for any day of the follicular phase. CONCLUSION(S): AMH concentrations vary across ovulatory menstrual cycles, showing a significant periovulatory decrease. The number of small antral follicles can be estimated from preovulatory AMH levels with relevance for patient management. CLINICAL TRIAL REGISTRATION NUMBER: NCT01802060.

Prospective randomized trial comparing magnetic resonance imaging (MRI)-guided in-bore biopsy to MRI-ultrasound fusion and transrectal ultrasound-guided prostate biopsy in patients with prior negative biopsies.

BACKGROUND: A significant proportion of prostate cancers (PCas) are missed by conventional transrectal ultrasound-guided biopsy (TRUS-GB). It remains unclear whether the combined approach using targeted magnetic resonance imaging (MRI)-ultrasound fusion-guided biopsy (FUS-GB) and systematic TRUS-GB is superior to targeted MRI-guided in-bore biopsy (IB-GB) for PCa detection. OBJECTIVE: To compare PCa detection between IB-GB alone and FUS-GB + TRUS-GB in patients with at least one negative TRUS-GB and prostate-specific antigen ≥4 ng/ml. DESIGN, SETTING, AND PARTICIPANTS: Patients were prospectively randomized after multiparametric prostate MRI to IB-GB (arm A) or FUS-GB + TRUS-GB (arm B) from November 2011 to July 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The study was powered at 80% to demonstrate an overall PCa detection rate of ≥60% in arm B compared to 40% in arm A. Secondary endpoints were the distribution of highest Gleason scores, the rate of detection of significant PCa (Gleason ≥7), the number of biopsy cores to detect one (significant) PCa, the positivity rate for biopsy cores, and tumor involvement per biopsy core. RESULTS AND LIMITATIONS: The study was halted after interim analysis because the primary endpoint was not met. The trial enrolled 267 patients, of whom 210 were analyzed (106 randomized to arm A and 104 to arm B). PCa detection was 37% in arm A and 39% in arm B (95% confidence interval for difference, -16% to 11%; p=0.7). Detection rates for significant PCa (29% vs 32%; p=0.7) and the highest percentage tumor involvement per biopsy core (48% vs 42%; p=0.4) were similar between the arms. The mean number of cores was 5.6 versus 17 (p<0.001). A limitation is the limited number of patients because of early cessation of accrual. CONCLUSIONS: This trial failed to identify an important improvement in detection rate for the combined biopsy approach over MRI-targeted biopsy alone. A prospective comparison between MRI-targeted biopsy alone and systematic TRUS-GB is justified. PATIENT SUMMARY: Our randomized study showed similar prostate cancer detection rates between targeted prostate biopsy guided by magnetic resonance imaging and the combination of targeted biopsy and systematic transrectal ultrasound-guided prostate biopsy. An important improvement in detection rates using the combined biopsy approach can be excluded.

Synergism of RAD and cyclosporin A in prevention of acute rat corneal allograft rejection.

PURPOSE: The novel immunosuppressant RAD, 40-0-(2-hydroxy-ethyl)-rapamycin, has synergistic effects with cyclosporin A. The aim of this study was to evaluate the combined effect of RAD and cyclosporin A in the prevention of acute allograft rejection after murine corneal transplantation. METHODS: Fisher donor corneas were implanted into Lewis recipients. Postoperative evaluation included slit-lamp biomicroscopy and immunohistology. Treatment groups were comprised of rats treated orally with RAD 2.5 mg/kg/day, cyclosporin A 10 mg/kg/day, RAD 1.5 mg/kg/day plus cyclosporin A 5 mg/kg/day. RESULTS: Therapy with RAD 2.5 mg/kg and cyclosporin A 10 mg/kg led to a statistically significant and comparable prolongation of transplant survival. However. combination therapy was significantly superior. There was a significant reduction in the number of infiltrating cells in the animals treated with RAD and cyclosporin A. CONCLUSIONS: This is the first study on the efficacy of a double drug regimen with RAD and cyclosporin A for the control of acute corneal allograft rejection. Combination therapy resulted in superior graft survival.

Efficacy of a herbal preparation in patients with functional dyspepsia: a meta-analysis of double-blind, randomized, clinical trials.

A meta-analysis was performed of double-blind, randomized clinical studies that evaluated the efficacy of the herbal preparation Iberogast in patients with functional dyspepsia. All studies had the same duration and used the same dosage of active treatment and the same primary outcome measure, a dyspepsia-specific gastrointestinal symptom score. Of the 592 trial participants, 196 were treated with Iberogast and 192 with placebo or cisapride (positive control). The individual studies all showed a substantial improvement of symptoms with Iberogast but varying results regarding its statistically significant superiority to placebo. The meta-analysis of all studies, however, demonstrated a clear, highly significant overall therapeutic effect of Iberogast in the treatment of functional dyspepsia. Tolerability of the preparation was excellent.