Intravenous prostaglandin E1 (alprostadil) bolus in ductus arteriosus-dependent CHD: valid or absolutely contraindicated?

The use of prostaglandin E1 is well documented in ductus arteriosus-dependent CHD or in neonatal pulmonary pathologies that cause severe pulmonary hypertension. The intravenous infusion is well established in loading infusion and maintenance with an onset of action of 30 minutes until 2 hours or even more. Our aim is to report three patients with pulmonary atresia that presented hypercyanotic spell due to a ductal spasm during cardiac catheterisation in whom the administration of a bolus of alprostadil reversed the spasm and increased pulmonary flow, immediately stabilising the condition of the patients allowing subsequent successful stent placement with no serious complications or sequelae after the administration of the bolus. More studies are needed to make a recommendation regarding the use of alprostadil in bolus in cases where the ductal spasm might jeopardise the life of the patient.

Combination therapy for Sneddon syndrome to reduce the incidence of cerebrovascular complications.

BACKGROUND: Sneddon syndrome is an occlusive vasculopathy that presents clinically with generalized livedo racemosa on the skin and transient ischemic attacks, strokes, and cognitive or motor deficits in the central nervous system. Antiplatelet or anticoagulant therapy is recommended. Due to the limited therapeutic efficacy and the resulting serious complications, we propose combination therapy with additional infusion cycles of alprostadil and captopril and report initial long-term results. PATIENTS AND METHODS: We performed a systematic retrospective analysis of all patients with primary Sneddon syndrome who received combination therapy in our clinic between 1995 and 2020. Therapeutic outcomes were evaluated using descriptive statistics compared to historical controls receiving monotherapy. We also analyzed the event rate of complications when combination therapy was discontinued. RESULTS: During the 99.7 patient-years of follow-up, there were no transient ischemic attacks and the stroke rate dropped to 0.02 per patient-year. In comparison, the rates of transient ischemic attacks and strokes in the historical controls ranged from 0.08 to 0.035 per patient-year. After discontinuation of alprostadil therapy, eight events occurred in three patients. CONCLUSIONS: Combination therapy reduces the long-term incidence of ischemic events in patients with primary Sneddon syndrome.

Add-On Prostaglandin E1 in Venovenous Extracorporeal Membrane Oxygenation: A Randomized, Double-Blind, Placebo-controlled Pilot Trial.

Rationale: Prostaglandin E1 (alprostadil; PGE1), in addition to low-dose unfractionated heparin, increases the biocompatibility of extracorporeal systems and enhances the efficacy of artificial organs without increasing bleeding risk. Objectives: We investigated the safety and efficacy of PGE1 in adults receiving venovenous extracorporeal membrane oxygenation (ECMO). Methods: This study was a randomized, double-blind, placebo-controlled phase II pilot trial at two medical intensive care units at the Medical University of Vienna, Austria. Adults with venovenous ECMO were randomly assigned to receive an intravenous infusion of 5 ng/kg/min PGE1 or placebo (0.9% saline) in addition to standard anticoagulation with unfractionated heparin. Measurements and Main Results: The primary outcome was the rate of transfused packed red blood cells per ECMO day. Secondary outcomes were the incidence of and time to clinically overt bleeding and thromboembolic events. A post hoc subgroup analysis included only patients with coronavirus disease (COVID-19). Between September 2016 and April 2021, of 133 screened patients, 50 patients were randomized, of whom 48 received the assigned study medication (24 per group). The transfusion rate was similar between groups (0.41 vs. 0.39; P = 0.733). PGE1 was associated with fewer thromboembolic events (7 vs. 16; P = 0.020) and longer thromboembolism-free time (hazard ratio [HR], 0.302; P = 0.01), fewer clinically overt bleeding events (2 vs. 11; P = 0.017), and longer bleeding-free time (HR, 0.213; P = 0.047). In patients with COVID-19 (n = 25), the HRs for clinically overt bleeding and thromboembolism were 0.276 (95% confidence interval, 0.035-2.186) and 0.521 (95% confidence interval, 0.149-1.825), respectively. Conclusions: Add-on treatment with PGE1 was safe but did not meet the primary endpoint of reducing the rate of red blood cell transfusions in patients receiving venovenous ECMO. Larger studies need to evaluate the safety and efficacy of additional PGE1 in ECMO. Clinical trial registered with EudraCT (2015-005014-30) and www.clinicaltrials.gov (NCT02895373).

Clinical evaluation of Alprostadil combined with Nimodipine in treatment of Cerebral Vasospasm after Subarachnoid Hemorrhage in elderly patients.

Objective: To analyze the clinical efficacy of alprostadil combined with nimodipine in the treatment of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in elderly patients. Methods: This is a retrospective study. According to different treatment methods, the elderly 100 patients with CVS after SAH hospitalized in Baoding First Central Hospital from March 2020 to May 2021 were randomly divided into control group and observation group, with 50 patients in each group. The control group was treated with nimodipine, while the observation group was additionally combined with alprostadil. The levels of inflammatory factors and hemorheological indexes were measured before and after treatment. The clinical efficacy was compared and the adverse reactions were observed of the two groups. Results: The overall clinical efficacy in the observation group (95.00%) was significantly higher than that in the control group (74.00%) (p<0.05). After treatment, serum tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), high-sensitivity C-reactive protein (hs-CRP) and hemorheological indexes such as plasma viscosity, whole blood viscosity at high shear, whole blood viscosity at low shear, hematocrit and platelet adhesion decreased significantly compared with those before treatment (p<0.05), which were more obvious in the observation group (p<0.05). During treatment, the rate of adverse reactions in the observation group was 12.00%, and that in the control group was 8.00%, without statistically significant difference between the two groups (p> 0.05). Conclusion: Alprostadil combined with nimodipine is markedly effective in the treatment of CVS after SAH in elderly patients. It can effectively reduce inflammatory factor levels and improve hemorheological indexes in patients, which is conducive to the repair of neurological function.

Evaluation of Inhaled Alprostadil in Hospitalized Adult Patients.

BACKGROUND: Intermittent inhaled alprostadil (iPGE1) may be a viable alternative to inhaled nitric oxide or epoprostenol for management of right ventricular failure, pulmonary hypertension (pHTN) or acute respiratory distress syndrome (ARDS). However, limited evidence exists regarding iPGE1 use in adults, ideal dosing strategies, or optimal use cases. OBJECTIVE: To describe the clinical characteristics of patients receiving iPGE1 and identify specific sub-populations warranting further research. METHODS: This was a single-center, retrospective, descriptive analysis of inpatients who received at least one dose of iPGE1. The primary outcome was to describe patient characteristics and alprostadil dosing strategies. Secondary outcomes included changes in respiratory support requirements, hemodynamics, and inotropic/vasoactive use. Outcomes were stratified and compared based on primary therapeutic indication (cardiac or pulmonary). RESULTS: Fifty-four patients received iPGE1 40 (75%) for pulmonary (pHTN or ARDS) and 14 (25%) for cardiac indications. There was no difference between indications in the number of patients de-escalated from level of respiratory (53% vs 57%, P = 0.76), inotropic (70% vs 57%, P = 0.39), or vasopressor support (78% vs 57%, P = 0.17). Furthermore, there was no significant improvement in cardiopulmonary parameters at multiple time intervals after iPGE1 initiation. CONCLUSION AND RELEVANCE: This is the largest study to date on the use of intermittent iPGE1 in adults. Alprostadil was safely utilized in novel populations; however, efficacy as evaluated by clinical or surrogate endpoints could not be demonstrated and further investigation is needed to determine its potential and optimal place in therapy.

Physical compatibility of alprostadil with selected drugs commonly used in the neonatal intensive care units.

This study aimed to determine the physical compatibility of alprostadil with 17 continuous infusion drugs commonly administered in neonatal intensive care units. Test samples were prepared in a laminar airflow hood. Alprostadil 20 mcg/ml was mixed with each drug in a 1:1 ratio, in two orders of mixing. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity. Visual examination was conducted by two observers by two methods: visual examination against a black and white background under normal fluorescent light and using a high-intensity monodirectional light. pH was measured as chemical stability predictor. Evaluations were performed immediately and 4 h after mixing. An additional visual control was performed at 24 h. Visual examination was positive or doubtful for the four drug combinations not considered compatible. Turbidity values were under 0.5 NTU throughout the study in all samples. No modifications of one pH unit or more was detected in any drug pair over time.Conclusion: Alprostadil was considered physical compatible with 13 drugs (adrenalin, amiodarone, calcium gluconate, dobutamine, dopamine, fentanyl, flecainide, furosemide, heparin, ketamine, midazolam, milrinone and morphine). Incompatibility could not be ruled out for 3 drugs (cisatracurium, dexmedetomidine and noradrenalin), and insulin was considered incompatible with alprostadil. What is Known: • Y-site administration is common in neonatal intensive care units, and volume of diluents and rate of infusions in newborns were lower than in adults which might result in high concentrations and prolonged contact time at Y-site administration. • Available data about compatibility of alprostadil with other drugs was scarce. What is New: • Alprostadil was compatible with 13 drugs commonly used in neonatal intensive care units. • Insulin was considered incompatible with alprostadil, and incompatibility cannot be ruled out for cisatracurium, dexmedetomidine and noradrenalin with alprostadil.

Frequency and anatomic distribution of arterial obstructions in patients with vasculogenic erectile dysfunction not responding to intracavernous prostaglandin.

Background: The extent of arterial disease in patients with erectile dysfunction (ED) non-responsive to intracavernosal injection of Alprostadil is of importance for therapeutic options. However, published evidence, in particular angiographically validated is scarce. Here we investigated arterial lesion patterns in this specific patient cohort by selective angiography. Patients and methods: A cohort of 239 patients received a clinical and duplex-sonographic workup for ED of suspected vascular origin. Duplex ultrasound of the cavernosal arteries was performed after intracavernosal injection of 10 µg Alprostadil. Consequently, standardized workup included grading of the erectile and determination of peak systolic velocity (PSV) and end-diastolic velocity (EDV) in both cavernosal arteries. PSV-values below 30 cm/sec indicated reduced arterial flow, whereas EDV-values above 15 cm/sec indicated a venous leak of the pudendal veins. All patients with suspected arterial ED based on duplex sonography underwent contrast-enhanced computed tomography. Endovascular therapy was carried out in ED patients not responsive or with significant side effects to PDE-5-inhibitors or Alprostadil by selective angiographic depiction of erection-related arteries. Results: 54 patients with a mean age of 61.2 (±9.8) years underwent angioplasty of erectionr elated arteries. Out of these 48/54 (89%) patients presented with an erection considered insufficient for penetration (E0-E3) subsequent to intracavernous application of 10 µg Alprostadil. 14/48 (29%) patients had bilateral arterial obstructions and 34/48 (71%) had unilateral disease. Commonly affected was the internal pudendal artery (n = 31, 65%), followed closely by the common penile artery (n = 30, 64%). The least affected arteries were the dorsal penile (n = 6, 13%), hypogastric (n = 4, 8%), common iliac (n = 4, 8%), cavernosal (n = 4, 8%), and inferior gluteal (n = 1, 2%) arteries. Conclusions: Arterial obstructions amenable to endovascular revascularization are frequent in patients non-responsive to intracavernosal prostaglandin administration. Therapeutic strategies in ED patients non-responsive to conservative measures should therefore consider endovascular treatment opportunities.

Intravesical alprostadil as a promising agent in BK virus-associated hemorrhagic cystitis: A report of a refractory case.

Allogeneic stem cell transplant recipients are at risk of BK virus-associated hemorrhagic cystitis. This condition causes a significant morbidity and worsens clinical outcomes. The standard cares for BK virus-associated hemorrhagic cystitis are saline irrigation and forced diuresis. Notably, several beneficial roles are proposed for antiviral and anti-inflammatory agents against BK virus-associated hemorrhagic cystitis. However, cases who are at risk of cystectomy remain refractory. Herein, we present a 13-year-old boy with severe hematuria by passing two months from his allogeneic stem cell transplantation. The laboratory work up showed high BK viremia >1.1 ×  108 copies/ml in this case's urine sample. The patient was treated with antiviral agents in combination with supportive care. Moreover, intravesical alum was administered, but no clinical benefits were achieved. Finally, intravesical alprostadil was prepared under the supervision of a pediatric clinical pharmacist. In this regard, an alprostadil solution was prepared by constitution of 250 µg alprostadil in 50 mL saline. After administrating the first dose of intravesical alprostadil, an acceptable clinical response was observed, and hematuria stopped. Of note, alprostadil induces platelet aggregation and vasoconstriction. Thus, bleeding can be controlled after the administration of intravesical alprostadil. This strategy may be associated with several side effects including bladder spasm. This study is the first report describing the special role of intravesical alprostadil in refractory cases of BK virus-associated hemorrhagic cystitis. In such refractory cases, clinicians can use intravesical alprostadil rather than invasive therapies in the treatment of BK virus-hemorrhagic cystitis.

Efficiency of intracavernosal alprostadil and oral clomiphene citrate combination treatment in penile vasculogenic erectile dysfunction patients accompanied by late-onset hypogonadism.

In this study, the efficiency of intracavernosal alprostadil + oral clomiphene citrate (CC) treatment in late-onset hypogonadism (LOH) accompanied by penile vasculogenic erectile dysfunction (PVED) in patients irresponsive to phosphodiesterase type 5 inhibitor treatment was evaluated. A total of 31 patients with concurrent PVED and LOH were included in the study. The patients were given intracavernosal alprostadil (10-20 µg) and oral CC (50 mg) every day for 12 weeks. Before and after treatment, a 15-question International Index of Erectile Function (IIEF-15) questionnaire, Erection Hardness Score (EHS), Sexual Encounter Profile (SEP)2 and SEP3 levels were analysed, and follicle stimulating hormone (FSH), luteinising hormone (LH), total testosterone and prostate-specific antigen (PSA) levels were measured. In all, 41.9% of patients had pure arterial deficiency, 19.3% had pure venous deficiency, and 38.7% had arterial + venous (mixed) deficiency. A significant increase was detected in total testosterone, FSH, LH and PSA values after treatment when compared to values before treatment (p < .001, p < .001, p < .001 and p = .034 respectively). A significant recovery was observed in IIEF-15 subscores, EHS and SEP2-SEP3 results. In PVED patients accompanied by LOH, intracavernosal alprostadil and oral CC combination is an efficient, low cost, safely applicable and tolerable treatment.

Is topical alprostadil an usable and reliable alternative to intracavernous injection for penile dynamic duplex ultrasonography?

No study has yet been done to evaluate topical alprostadil as a less invasive alternative vasoactive agent for Penile Dynamic Duplex Ultrasonography (PDDU) in the diagnosis of erectile dysfunction. The main aim of our study was to evaluate the usability and reliability of topical alprostadil for PDDU compared with standard intracavernous injection. A further objective was to determine the patients' preference between these two different approaches. During session A, patients received injection while during session B, they received topical alprostadil. Each patient underwent both sessions, 1 week apart from the other. A total of 80 patients were enrolled. After 20 min from drug administration, no significant difference was found between the two procedures in terms of peak systolic velocity and end-diastolic velocity, while Erection Hardness Score was significantly higher with injection. Patients reported less pain/discomfort during the procedure in case of topical alprostadil use and an overall preference towards this examination modality. Topical alprostadil could represent a usable and reliable alternative to intracavernous injection for PDDU, with less discomfort and greater preference by patients.

[Effects of alprostadil in ß-aminopropanitrile induced aortic dissection in a murine model].

Objective: To investigate the protective role of alprostadil on aortic dissection. Methods: 26 C57BL6 male mice were divided into control group (normal drinking water, n=13) and model group (1 g·kg-1·d-1 BAPN via drinking water, n=13). On day 14, mRNA expression of inflammatory-related genes as well as EP receptor families were detected by RT-PCR (n=6 each) and EP4 protein levels were determined by Western blot (n=7 each). Another 88 mice were divided into 3 groups: control group (n=22), model group (n=33) and treatment group (n=33). The mice in model group and treatment group were applied with BAPN (1 g·kg-1·d-1) via drinking water. The mice in treatment group received additional intraperitoneal injection with alprostadil (80 µg·kg-1·d-1) for 28 days. The mice in the control and model group received equal volume intraperitoneal injection with 0.9% saline respectively. The body weight and systolic blood pressure, the mortality and morbidity were monitored from the beginning until the designed end of the study. On day 28, the mice were sacrificed and aorta were fixed, embedded and sliced, followed by staining with HE and Victoria Blue. The distribution of EP4 was determined by immunohistochemistry in control (n=6) and model group (n=6). Furthermore, the concentration of PGE1 were tested among model (n=3) and treatment group (n=4). EP4 protein expression was determined in model group (n=7) and treatment group (n=6). Results: On day 14, mRNA expression level of MCP-1 ((2.74±1.55) vs. (1.00±0.49),<0.05) and MMP2((1.38±0.42) vs. (1.00±0.27), P<0.05) was significantly upregulated in model group compared with control group. Protein expression of EP4 receptor also increased in aorta in model group compared with control group (1.48±0.51 vs. 1.00±0.19, P<0.05). In the dissection area, the EP4 expression was also enriched compared with non-dissection area, particularly in endothelial cells and inflammatory cells on day 28. BAPN applied in drinking water (model and treatment groups) successfully induced the aortic dissection in mice, some mice died of the rupture. The elastic fibers were fractured, and the infiltrated immune cells were visible in dissected tissue. False lumen was formed. There was no dissection and death in the control group. Compared with control group, the morbidity and mortality rates were significantly increased in the model group (60.6%, 20/33, 30.3%, 10/33) and the treatment group (72.7%, 24/33, 24.2%, 8/33). The mortality and morbidity rates were similar between model and treatment groups. There is no difference in terms of SBP among three groups (P>0.05). Further study showed that after alprostadil injection, the blood concentration of PGE1 was increased in treatment group ((0.540±0.041 vs. 0.436±0.012)µmol/L, P<0.05). Besides, the EP4 receptor expression was downregulated in the treatment group compared to model group (0.60±0.30 vs. 1.00±0.20, P<0.05). Conclusion: EP4 expression is upregulated in BAPN induced aortic dissection mouse model. No protective effects are observed post alprostadil treatment in this model probably due to the reduced expression of EP4.

Effect of Alprostadil on Colorectal Anastomoses Under Relative Ischemia.

BACKGROUND: Anastomotic leak after colorectal surgery, which remains a serious clinical problem that causes augmented morbidity and mortality, is usually favored by ischemia. The aim of this study was to determine whether alprostadil may improve anastomotic wound healing under ischemic condition. METHODS: Ninety-three adult Wistar rats were randomized into three groups: control, ischemia (by devascularization along the first 2 cm at each anastomotic end), and ischemia plus alprostadil. Resection of a colonic segment at the colorectal junction and an anastomosis was performed. Animals were euthanized at 8 d. Surgical site infection, anastomotic leak, and grade of intra-abdominal adhesions using a validated scale were determined. Bursting pressure and tension were calculated and histologic examination of the anastomosis was performed. RESULTS: The ischemic group revealed an increased anastomotic leak rate (14/31 versus 3/31) and a lower bursting pressure and tension when compared to control group, validating therefore the experimental model. After intraperitoneal injection of alprostadil, anastomotic leak rate was significantly lower (5/31) and the bursting pressure and tension were significantly increased. Histologic examination revealed a lower presence of inflammatory cells, and a significantly higher neovascularization and a higher presence of fibroblasts in treated animals when compared with the ischemic group. CONCLUSIONS: Alprostadil may have a positive effect on colonic anastomotic wound healing under relative ischemic condition. Alprostadil administration increases anastomotic bursting pressure, decreases leak rate, and reverses most of the histological changes caused by blood flow decrease. These protective effects could be caused by vasodilation, stimulation of neovascularization, and immunomodulatory properties.

Use of intravenous alprostadil in patients with severe critical ischemia of the lower limbs.

OBJECTIVES: To determine the indications for the use, potential benefits, and adverse reactions of alprostadil in a group of Colombian patients. METHODS: A retrospective cross-sectional study was conducted in patients diagnosed with critical limb ischemia who received alprostadil in five hospitals in Colombia between September 2011 and July 2017. We reviewed the clinical records of each patient to obtain the sociodemographic and pharmacological variables, clinical stages, complications, comorbidities, reported effectiveness and adverse reactions. RESULTS: Sixty-one patients treated with alprostadil were evaluated; 50.8% of patients were men, and the average age of 72.5 ± 10.7 years. A total of 86.9% of patients were hypertensive, and 65.6% were diabetic. A total of 77.0% presented ulceration, and this condition was considered as a diabetic foot in 57.4% of patients. A total of 81.9% of patients were classified as Fontaine stage 4; 60.7% received therapy as initially indicated, with an average of 19 days of alprostadil use. Regarding the therapy results, 58.0% of the patients with ulcers or trophic lesions showed improvement, 86.2% showed improvement of pain, and the limb was saved in 72.1% of patients. CONCLUSIONS: Critical limb ischemia was presented by patients with advanced age and high cardiovascular risk who were treated during severe and advanced stages where therapeutic options are limited. Treatment with alprostadil achieved satisfactory results with improvement in ulcers, pain, and limb salvage rates in this series of patients.

Efficacy of alprostadil in preventing contrast-induced nephropathy in patients undergoing percutaneous coronary intervention: A multicenter prospective randomized controlled trial.

BACKGROUND: The role of alprostadil on the prevention of contrast-induced nephropathy (CIN) still remains controversial. The purpose of this study was to examine the effects of short-term alprostadil on the incidence of CIN in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: A total of 480 patients with coronary heart disease undergoing PCI were enrolled in our study and randomly assigned to two groups. The control group (n = 240) was given only hydration therapy and the alprostadil group (n = 240) received intravenous administration of 20 ug/day (diluted with 100 ml normal saline) from 0.5∼1 hr before to 3 days after operation on the basis of hydration. The primary endpoint of the study was the incidence of CIN, which was defined as an increase in SCr concentration ≥ 44.2 umol/l or ≥25% above baseline within 48 hr∼72 hr after exposure of contrast media. RESULTS: The incidence of CIN was significantly lower in the alprostadil group than that in the control group (6.25% vs 11.67%, P = 0.038). Multivariate logistic regression analysis showed that alprostadil was the protective factor of CIN (OR = 0.699, 95% CI 0.542-0.902, P = 0.006). The benefits against CIN were consistent in prespecified high-risk patients with diabetes mellitus (P = 0.003). In addition, we also found that hs-CRP and blood homocysteine values after PCI were significantly lower in the alprostadil group than those in the control group. CONCLUSION: Prophylactic administration of alprostadil may prevent against CIN in coronary heart disease patients undergoing elective PCI, particularly in high-risk patients with diabetes mellitus.

Use of prostaglandins in duct-dependent congenital heart conditions.

Congenital heart disease (CHD) remains a leading cause of infant mortality, which is even higher in infants with undiagnosed duct-dependent CHDs. Up to 39%-50% of infants with critical CHD are being discharged undiagnosed from the hospital. Infants with duct-dependent critical CHD remain well during the fetal period and may deteriorate when the ductus arteriosus (commonly called 'duct') closes after birth. It is critical to open or maintain ductus arteriosus patent in infants with duct-dependent CHDs. Prostaglandin E1 (alprostadil marketed as 'Prostin VR ') and prostaglandin E2 (dinoprostone) are used to maintain a patent ductus arteriosus and the dose of medication depends on the clinical presentation. Delay in starting prostaglandin infusion can have deleterious effects on infants and can even lead to death. These infants often present as an emergency, and professionals caring for these infants need to have a good understanding of these conditions and medications used for ductal patency.

The protective effect of Papaverine and Alprostadil in rat testes after ischemia and reperfusion injury.

OBJECTIVE: To investigate the effect of papaverine and alprostadil on testicular torsion-detorsion injury in rats. MATERIALS AND METHODS: A total of 40 male Wistar-Albino rats were used in this study. Four hours of right testicular torsion was applied to each group, excluding sham operated group. The torsion-detorsion (T/D), T/D + papaverine and T/D + alprostadil groups received saline, papaverine and alprostadil at the same time as surgical detorsion, respectively. At 14 days after the surgical detorsion, ischaemic changes and the degree of damage were evaluated with Cosentino scoring and the Johnson tubular biopsy score (JTBS). RESULTS: JTBS was determined as 8.8±2.7 in the Sham group, 5.08±1.9 in the T/ D+papaverine group, 5.29±2.3 in the T/D +alprostadil group and 2.86±1.9 in the TD group. The JTBS was determined to be statistically significantly high in both the T/D + papaverine group and the T/D + alprostadil group compared to the T/D group (p=0.01, p=0.009). In the T/D + papaverine group, 3 (43 %) testes were classified as Cosentino 2, 3 (43%) as Cosentino 3 and 1 (14 %) as Cosentino 4. In the T/D +alprostadil group, 5 (50 %) testes were classified as Cosentino 2, 3 (30 %) as Cosentino 3 and 2 (20%) as Cosentino 4. CONCLUSION: The present study indicated that spermatic cord administration of alprostadil and papaverine showed a protective effect against ischemia/reperfusion injury after right-side testes torsion and histological changes were decreased after testicular ischemia reperfusion injury.

[Panax notoginseng extract combined with alprostadil in treatment of arteriosclerosis obliterans: Meta-analysis].

To evaluate the clinical efficacy of Panax notoginseng extract combined with alprostadil in the treatment of arteriosclerosis occlusion and investigate its effects on the degree of atherosclerosis. CNKI, Wanfang, VIP journal database, Chinese biomedical literature database(CBM), PubMed, the Cochrane Library and Science Citation Index(SCI) database were searched between inception to December 2017 for relevant studies. Two researchers independently screened and extracted the literature in strict accordance with the inclusion criteria and exclusion criteria. The bias risk assessment method recommended by Cochrane was used to evaluate the bias risk and extract data, and then Review Manager 5.3 was used for Meta analysis. 10 RCTs involving a total of 1 032 cases were included in the study. Analysis results showed that the P. notoginseng extract combined with alprostadil had higher clinical efficacy than alprostadil alone in the treatment of arteriosclerosis occlusion disorder, with statistically significant difference(OR=6.39, 95%CI[3.97, 10.30], P<0.000 01); the atherosclerosis was obviously improved, including ankle brachial index(ABI) (MD=0.08, 95%CI[0.04, 0.13], P=0.000 3), toe brachial index(TBI) (MD=0.09, 95%CI[0.05, 0.12], P<0.000 01), and maximum walking distance(WD) (MD=471.62, 95%CI[383.54, 559.70], P<0.000 01). Studies have shown that P. notoginseng extract combined with the conventional treatment had significantly improved clinical efficacy in the treatment of arteriosclerosis occlusion, and could improve the atherosclerosis degree of lower extremities. However, the quality of the included literature was not high, in addition, due to the small number of included literature as well as bias and low-quality bias in some of the literature, more high quality RCTs are still needed to further verify the clinical effect of P. notoginseng extract in the treatment of arteriosclerosis occlusion.

Sexual Rehabilitation After Treatment For Prostate Cancer-Part 2: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).

INTRODUCTION: Sexual dysfunction is common in patients after radical prostatectomy (RP) for prostate cancer. AIM: To provide the International Consultation for Sexual Medicine (ICSM) 2015 recommendations concerning management strategies for post-RP erectile function impairment and to analyze post-RP sexual dysfunction other than erectile dysfunction. METHODS: A literature search was performed using Google and PubMed database for English-language original and review articles published up to August 2016. MAIN OUTCOME MEASURES: Levels of evidence (LEs) and grades of recommendations (GRs) are provided based on a thorough analysis of the literature and committee consensus. RESULTS: Nine recommendations are provided by the ICSM 2015 committee on sexual rehabilitation after RP. Recommendation 6 states that the recovery of postoperative erectile function can take several years (LE = 2, GR = C). Recommendation 7 states there are conflicting data as to whether penile rehabilitation with phosphodiesterase type 5 inhibitors improves recovery of spontaneous erections (LE = 1, GR = A). Recommendation 8 states that the data are inadequate to support any specific regimen as optimal for penile rehabilitation (LE = 3, GR = C). Recommendation 9 states that men undergoing RP (any technique) are at risk of sexual changes other than erectile dysfunction, including decreased libido, changes in orgasm, anejaculation, Peyronie-like disease, and changes in penile size (LE = 2, GR = B). CONCLUSION: This article discusses Recommendations 6 to 9 of the ICSM 2015 committee on sexual rehabilitation after RP. Salonia A, Adaikan G, Buvat J, et al. Sexual Rehabilitation After Treatment For Prostate Cancer-Part 2: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017;14:297-315.

Efficacy and Safety of Alprostadil in Patients with Peripheral Arterial Occlusive Disease Fontaine Stage IV: Results of a Placebo Controlled Randomised Multicentre Trial (ESPECIAL).

OBJECTIVES: The aim was to assess the efficacy and safety of alprostadil in patients with peripheral arterial occlusive disease (PAOD) Fontaine Stage IV. METHODS: This was a multinational, prospective, randomised, double blind, placebo controlled, parallel group trial. Patients with Stage IV PAOD were equally randomised to either 4 weeks of alprostadil treatment twice daily or to placebo treatment twice daily. The primary efficacy variables were the rate of complete healing of all necrosis and ulceration 12 weeks after the end of treatment and the frequency of major amputations 24 weeks after the end of treatment. RESULTS: A total of 840 patients were randomised between 2004 and 2013. At baseline, no major differences between treatment groups were found. The rate of "complete healing" was 18.4% in patients on alprostadil and 17.2% in patients on placebo. The rates of "major amputations" were 12.6% in patients on alprostadil and 14.6% in patients on placebo. The adjusted difference between alprostadil and placebo including their 95% confidence intervals was 1.1 (-4.0 to 6.3) for "complete healing" and -2.1 (-6.7 to 2.5) for "major amputations." In the subgroup of diabetic patients the rates of major amputations were numerically lower in the alprostadil than placebo group (10.6% vs. 17.4%). Within the total cohort a non-significant difference in "decrease in ulcer area ≥50%" was reached in 30.2% of patients on alprostadil and in 24.3% of patients on placebo at end of treatment. CONCLUSIONS: In this study, superiority of alprostadil over placebo could not be shown. Nevertheless, a slight numerical but not clinically relevant advantage for alprostadil emerged from the "area decrease of ulcers by ≥ 50%," indicating that a healing effect may have started. The results have to be considered in the light of several limitations in study design and conduct.