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AbstractBackgroundBK virus (BKV)‐associated hemorrhagic cystitis (BKV‐HC) is a severe complication after hematopoietic stem cell transplantation (HSCT). Cidofovir (CDV) has emerged as an effective agent for the treatment of BKV nephropathy, but its use for BKV‐HC in pediatric HSCT recipients has not yet been established as a standard therapy.Patient and methodsWe retrospectively investigated the efficacy and safety of CDV therapy for patients with BKV‐HC at a single institution and analyzed the clinical management outcomes.ResultsFrom April 2009 to July 2011, 12 patients developed BKV‐HC at a median of 37 days after transplant (range 15–59 days). The cumulative incidence was 9% and the median peak of the urine BKV load was 2.5 × 1010 copies/mL (range 1.4 × 109–1.2 × 1011 copies/mL). Eleven patients received intravenous CDV (5 mg/kg/dose, with probenecid), whereas 1 patient received CDV (5 mg/kg/dose, without probenecid) intravesically. The median duration of therapy was 25 days (range 9–73 days), and a median of 2 doses was given (range 1–4). A reduction of ≥1 log in the BKV load was found in 11 patients, while 1 patient did not have any significant change in BKV load. Clinical improvement was observed in all cases, and no HC‐related death was observed. CDV‐related toxicity occurred in 1 patient (8%) and spontaneously resolved.ConclusionsCDV appears to be an effective and safe treatment for BKV‐HC in pediatric HSCT recipients, but prospective trials are warranted to support its use.

Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim: Our aim was to determine the effects of follicular-phase kisspeptin-54 treatment on menstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7–14 (n = 5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin-54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shorter mean length of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P < .01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P < .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P < .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.

Background— Cardiac manifestations of Marfan syndrome include aortic root dilation and mitral valve prolapse (MVP). Only scant data exist describing MVP in patients with Marfan syndrome undergoing aortic root replacement. Methods and Results— We retrospectively analyzed data from 166 MFS patients with MVP who were enrolled in a prospective multicenter registry of patients who underwent aortic root aneurysm repair. Of these 166 patients, 9% had mitral regurgitation (MR) grade >2, and 10% had MR grade 2. The severity of MVP and MR was evaluated by echocardiography preoperatively and ≤3 years postoperatively. Forty-one patients (25%) underwent composite graft aortic valve replacement, and 125 patients (75%) underwent aortic valve–sparing procedures; both groups had similar prevalences of MR grade >2 ( P =0.7). Thirty-three patients (20%) underwent concomitant mitral valve (MV) intervention (repair, n=29; replacement, n=4), including all 15 patients with MR grade >2. Only 1 patient required MV reintervention during follow-up (mean clinical follow-up, 31±10 months). Echocardiography performed 21±13 months postoperatively revealed MR >2 in only 3 patients (2%). One early death and 2 late deaths occurred. Conclusions— Although the majority of patients with Marfan syndrome who undergo elective aortic root replacement have MVP, only 20% have concomitant MV procedures. These concomitant procedures do not seem to increase operative risk. In patients with MR grade ≤2 who do not undergo a concomitant MV procedure, the short-term incidence of progressive MR is low; however, more follow-up is needed to determine whether patients with MVP and MR grade ≤2 would benefit from prophylactic MV intervention.

Adult fibrosarcoma, defined by the World Health Organization as a ‘malignant neoplasm composed of fibroblasts with variable collagen production and, in classical cases, a “herringbone” architecture’, is a very rare soft tissue sarcoma. Once considered the most common adult sarcoma, the incidence of adult fibrosarcoma has declined dramatically over the past several decades. This is due to (i) evolution in the classification of soft tissue tumours (ii) recognition of clinically, morphologically and genetically distinctive subtypes of fibrosarcoma and (iii) increased understanding of the many other mesenchymal and non‐mesenchymal tumours that may mimic fibrosarcoma. This review article will summarize the current state of our knowledge about strictly defined adult fibrosarcoma and discuss important entities in its differential diagnosis, including various fibrosarcoma variants, monophasic synovial sarcoma and other potential mesenchymal and non‐mesenchymal mimics.

Introduction Pulmonary vein isolation is an effective therapy for curing symptomatic atrial fibrillation (AF). While it is known the severity of left atrial (LA) enlargement affect the success of AF ablation, little is known the impact of intracardiac pressure on the ablation outcome. Methods This prospective study consisted of 63 patients (mean age 57±9 years, 73% male) who underwent catheter-based pulmonary vein isolation for drug refractor symptomatic AF (48% paroxysmal, 52% persistent). All patients underwent simultaneous echocardiography and haemodynamic measurements including left ventricular end systolic pressure (LVEDP), mean left atrial pressure (LAP) and dP/dtmax using Millar catheter at the time of procedure during AF. Left atrial volume (LAV) was measure by biplane area length method. Recurrence of AF was defined as episodes of AF more than 5 min documented in 24h ambulatory ECG or event monitor. Results After a mean follow-up duration of 16±7 months, AF elimination off anti-arrhythmic drugs was achieved in 70 % (44/63) of patients. Among the echographic and haemodynamic measurements, the baseline LAV and mean LAP were 57.62±25.39 ml and 12.19±4.57 mm Hg in AF free patients compared to 81.20±40.88 ml (p=0.02) and 16.46±4.14 mm Hg (p=0.01) in AF recurrence groups. Univariate and multivariate analysis showed LAP was the only independent predictor of the recurrence with an adjusted odd ratio of 1.27 (95% CI 1.04 to 1.54, p=0.03, table). Conclusion LAP is a determinant of AF recurrence after AF ablation. Therapies towards reduction of LA filling pressure, especially in patients with elevated LAP, may improve the outcome of ablation. Table Baseline clinical characters in the recurrence group and non-recurrence group Non-recurrence (N=44) recurrence (N=19) Univariate Multivariate P 95% CI P 95% CI Age (ys) 57.39±9.92 59.26±10.47 0.49 0.97, 1.08 – – AF type, persistent AF no. (%) 23 (53%) 10 (50%) 0.97 0.34, 2.98 – – AF duration (ys) 5.84±5.43 8.08±7.66 0.20 0.99, 1.05 – – LA volume (mL) 57.62±25.39 81.20±40.88 0.02 1.01, 1.05 0.30 0.99, 1.05 LVEDP (mm Hg) 10.25±14.54 11.25±5.75 0.81 0.96, 1.06 – – dP/dt max (mm Hg/s) 1294.02±337.13 1211.77±225.36 0.47 0.99, 1.02 – – Mean LAPmean (mm Hg) 12.19±4.57 16.46±4.14 0.01 1.06, 1.50 0.02 1.04, 1.54 Pulmonary vein isolation is an effective therapy for curing symptomatic atrial fibrillation (AF) but the success rate ranged wide. This study aimed to investigate the effect of LAP on AF recurrence.

Background Neurohormonal dysregulation contributes to heart failure (HF) progression. We sought to determine the effect of cardiac resynchronisation therapy (CRT) on the nerve growth factor (NGF), a biomarker that promotes the maturation, and survival of sympathetic nerve endings, and amino-terminal propeptide of type III procollagen (PIIINP), a marker of type III collagen synthesis. Methods This prospective study enrolled 20 healthy age-matched controls and 45 consecutive patients (pts) who received CRT-D. NYHA class, distance of 6-min walk and echocardiography and plasma concentrations of NGF, PIIINP, b-type natriuretic peptide (BNP), norepinephrine (NE), epinephrine (EPI) and dopamine (DA) were measured before and 6 month after CRT. Response to CRT was defined as ≥15% reduction in left ventricular end-systolic volume index (LVESVI) at 6-month follow-up. Results The baseline BNP (557±692 vs 47±35, p<0.01) and PIIINP (8.22±3.76 vs 5.36±1.47, p<0.01) were elevated in HF compared to controls, while NGF, NE, EPI and DA levels were not different. Twenty two of 45 pts (49%) responded to CRT. The responder group demonstrated significant decrease only in BNP level (p=0.04) at 6-month follow-up, parallelling with the clinical improvements (table 1). The baseline PIIINP was lower in CRT responders than non-responders (p=0.04), and it correlated with the reduction of LVESVI (p=0.01, r=−0.50) after CRT. The further multivariate analysis showed only the plasma PIIINP level among clinic characters and all the biomarkers can predict the improvement of LVESV index (OR=8.33, P=0.01). Conclusion The low PIIINP level, which is consistent with possible less cardiac fibrosis and a more plastic ventricle at baseline, is associated with CRT responsiveness. Contrary to previous reports, the NGF levels were not reduced during HF and that there was no NGF rebound in CRT responders.