Outcomes of Alprostadil As an Adjuvant Therapy with Indirect Angiosomal Revascularization in Patients with Critical Limb Ischemia after Failure of Direct Revascularization.

BACKGROUND: This study was carried out to assess the effectiveness of alprostadil (prostaglandin E1) when used as an adjuvant therapy with indirect revascularization in patients with critical limb ischemia (CLI) after the failure of direct revascularization (DR). METHODS: At our centers, 120 patients suffering from infrainguinal peripheral arterial disease with CLI underwent a failed trial of DR procedure, all revascularization procedures were endovascular. Median follow-up was 2 years and 2.5 years for patients with and without diabetes mellitus (DM). In the alprostadil group, the mean age was 63.41 ± 12.52; 36 (60%) for males and 24 (40%) for females. Post-endovascular intervention alprostadil was administrated immediately postoperatively by intravenous infusion of 40 µg alprostadil diluted in 100 ml of normal saline, over 2 hr every 12 hr for 6 days. RESULTS: In the alprostadil group, the mean ± standard deviation (SD) of the baseline ankle-brachial index (ABI) was 0.45 ± 0.175, while the mean ± SD of ABI at the end of our study was 0.65 ± 0.216 with a difference from the baseline of 0.2 ± 0.041 (P value = 0.08, <0.05 meaning that it is significant). Our 1-month primary patency rate was 93.3%, while our 3- and 6-month patency rate was 92.9%. In the control group, the mean ± SD of the baseline ABI was 0.68 ± 0.22, while the mean ± SD of ABI at the end of our study was 0.69 ± 0.23 with a difference from the baseline of 0.01 ± 0.01 (P value >0.05 meaning that it is nonsignificant) 1-month patency rate was 89%, while 3- and 6-month patency rate was 75%. When we compared the patient's leg vessels before and after our intervention, we found that the percentage of the no-runoff-vessels group decreased from 10 (16.7%) to 4 (6.67%). One-runoff-vessel group percentage dropped from 40 (66.7%) to 36 (60%), whereas, in the two-runoff-vessel group, the percentage increased from 10 (16.7%) to 20 (33.3%). We evaluate leg arteries; we do no pedal arch intervention in the alpostradil group. Out of the total of 60 patients, limb salvage occurred in 58 (96.7%) patients, and 2 (3.3%) patients underwent below-the-knee amputation before the study ended. CONCLUSIONS: Our results show the efficacy and safety of alprostadil as an adjuvant therapy with indirect angiosomal revascularization in patients with tissue loss due to CLI.

Congenital Eyelid Imbrication and Floppy Eyelid Syndromes Complicated by Eversion due to Prostaglandin E Infusion in a Patient With Trisomy 21 and Tetralogy of Fallot.

Congenital eyelid imbrication syndrome is a rare eyelid finding where a long upper lid overlaps the lower lid when the eyes are closed. To date, congenital eyelid imbrication syndrome has been described in the literature less than 10 times. We present a case of congenital eyelid imbrication syndrome in a patient with trisomy 21 and tetralogy of Fallot on a prostaglandin E infusion to maintain a patent ductus arteriosus prior to definitive heart surgery. While on the infusion, the patient developed peripheral edema and flushing due to vasodilation. This coincided with eyelid swelling, conjunctival chemosis, and eversion of the eyelids. Upon cessation of the prostaglandin E1 infusion, his eyelid eversion resolved.

The penile duplex ultrasound: How and when to perform it?

BACKGROUND: Because it is a superficial structure, the penis is ideally suited to ultrasound imaging. A number of disease processes, including Peyronie's disease, penile fractures and tumors, are clearly visualized with ultrasound. Baseline and dynamic assessment of cavernosal arterial changes after pharmaco-stimulation with alprostadil allows standardized diagnosis of arterial and venogenic causes of erectile dysfunction (ED). OBJECTIVE: To illustrate how to correctly perform flaccid and dynamic penile duplex ultrasound (D-PDU) and in which patients to recommend it. MATERIALS/METHODS: An extensive search of the literature was carried out on Pubmed with the insertion of the following Medical Subjects Headings (MeSH) terms and keywords "penile color Doppler ultrasound" "peak systolic velocity" "end-diastolic velocity", "acceleration time", "resistance index". EVIDENCE: In our experience, arterial erectile dysfunction is identified after standardized intracavernous injection (ICI) of alprostadil (10 mcg) when values of peak systolic velocity (PSV) are <35 cm/s and, in the most severe forms, for values <25 cm/s. Arterial insufficiency can also be identified by increased acceleration time (AT) values (>110 ms) and/or by a lack of visualization of helicine arteries at power Doppler mode along with incomplete achievement of penile rigidity. The veno-occlusive incompetence is determined when end-diastolic velocity (EDV) values are >4.5-5 cm/s or in the case of resistance index (RI) values <0.75. The assessment of additional surrogate markers of endothelial dysfunction, that is, intima-media thickness, mean platelet volume (MPV), endothelial progenitor cells (EPC), endothelial cell specific molecule-1(endocan) are also useful in assessing the patient's cardiovascular risk but are still considered investigational in the interpretation of D-PDU results. CONCLUSION: D-PDU scan after ICI with vasoactive drugs is a safe procedure and represents the gold standard for the diagnostics of penile pathologies and should be performed in men with ED not responding to oral conventional therapies and/or in those requiring accurate stratification of cardiovascular risk.

Alternative Treatment for Erectile Dysfunction: a Growing Arsenal in Men's Health.

PURPOSE OF REVIEW: To highlight and review encouraging preliminary studies behind several alternative products and interventions for erectile dysfunction (ED). RECENT FINDINGS: Alternative treatments for ED are becoming more prevalent with increased consumer interest. "Natural" products are sold online, and numerous clinics offer various off-label and investigational interventions. These alternative treatments have demonstrated varying degrees of efficacy in randomized trials and meta-analyses, but none of these interventions has robust enough evidence to be considered first-line therapy. These treatments may find a role in combination with guideline treatments or may be used in novel penile rehabilitation research protocols. With growing interest in alternative treatment for men's health, an awareness of the literature is imperative for patient counsel. Alternative treatments, like L-arginine, have a growing body of evidence for efficacy in combination with PDE5i, and low-intensity shock wave therapy and stem cell therapy continue to demonstrate encouraging outcomes in ED trials.

Lumbar Spinal Stenosis and Potential Management With Prostaglandin E1 Analogs.

ABSTRACT: Lumbar spinal stenosis is one of the most commonly diagnosed spinal disorders worldwide and remains a major cause for surgery in older adults. Lumbar spinal stenosis is clinically defined as a progressive degenerative disorder with low back pain and associated neurogenic intermittent claudication. Conservative and surgical management of lumbar spinal stenosis has been shown to be minimally effective on its symptoms. A treatment option that has not been investigated in the United States is the utilization of prostaglandin E1 analogs, which have been used primarily in Japan for the treatment of lumbar spinal stenosis since the 1980s. The vasodilatory and antiplatelet aggregation effects of prostaglandin E1 presumably improve symptoms of lumbar spinal stenosis by increasing blood flow to the spinal nerve roots. This brief report examines the potential vascular pathology of lumbar spinal stenosis, reviews evidence on the use of prostaglandin E1 analog limaprost in Japan for lumbar spinal stenosis, and briefly discusses misoprostol as a possible alternative in the United States. The studies summarized in this report suggest that prostaglandin E1 analogs may provide benefit as a conservative treatment option for patients with lumbar spinal stenosis. However, higher-quality studies conducted in the United States and comparison with other currently used conservative treatments are required before it can be recommended for routine clinical use.

Alprostadil Injection Attenuates Coronary Microembolization-Induced Myocardial Injury Through GSK-3ß/Nrf2/HO-1 Signaling-Mediated Apoptosis Inhibition.

OBJECTIVE: Coronary microembolization (CME) results in progressive contractile dysfunction associated with cardiomyocyte apoptosis. Alprostadil injection improves microcirculation, which is effective in treating various cardiovascular disorders. However, the therapeutic effects of alprostadil in CME-induced myocardia injury remain unknown. Therefore, we evaluated the effects of alprostadil injection on cardiac protection in a rat model of CME and explored the underlying mechanisms. METHODS: A rat model of CME was established by injecting polyethylene microspheres into the left ventricle. After injection of microspheres, rats in the alprostadil group received alprostadil via tail vein within 2 minutes. Cardiac function, histological alterations in myocardium, serum c-troponin I (cTnI) levels, myocardium adenosine triphosphate (ATP) concentrations, the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) content in myocardium, and myocardial apoptosis-related proteins were detected 12 hours after CME modeling. RESULTS: Compared with the Sham group, ATP concentrations, SOD activity in the myocardium, and cardiac function were significantly decreased in a rat model of CME. In addition, serum cTnI levels, MDA content, expression levels of pro-apoptotic proteins, and the number of TUNEL-positive nuclei were remarkably higher in CME group than those in the Sham group. However, alprostadil treatment notably reduced serum cTnI levels and expression levels of pro-apoptotic proteins, while noticeably improved cardiac function, and accelerated SOD activity in the myocardium following CME. Additionally, it was unveiled that the protective effects of alprostadil injection inhibit CME-induced myocardial apoptosis in the myocardium potentially through regulation of the GSK-3ß/Nrf2/HO-1 signaling pathway. CONCLUSION: Alprostadil injection seems to significantly suppress oxidative stress, alleviate myocardial apoptosis in the myocardium, and improve cardiac systolic and diastolic functions following CME by regulating the GSK-3ß/Nrf2/HO-1 signaling pathway.

Effects of prostaglandin E1 nebulization of ventilated lung under 60%O2 one lung ventilation on patients' oxygenation and oxidative stress: a randomised controlled trial.

BACKGROUND: High FiO2 during one-lung ventilation (OLV) can improve oxygenation, but increase the risk of atelectasis and oxidative stress. The aim of this study was to analyze whether Prostaglandin E1 (PGE1) can improve oxygenation and attenuate oxidative stress during OLV under a lower FiO2. METHOD: Ninety patients selectively undergoing thoracotomy for esophageal cancer were randomly divided into three groups (n = 30/group): Group P (FiO2 = 0.6, inhaling PGE1 0.1 µg/kg), Group L (FiO2 = 0.6) and Group C (FiO2 = 1.0). The primary outcomes were oxygenation and pulmonary shunt during OLV. Secondary outcomes included haemodynamics, respiratory mechanics and oxidative stress in serum. RESULTS: Patients in Group P had significantly higher PaO2 and lower shunt fraction in 30 min of OLV compared with Group L. Compared with Group C, patients in Group P had similar levels of PaO2/FiO2 in 60 min and higher levels of PaO2/FiO2 at 2 h during OLV. The levels of PvO2 and SvO2 in Group P and Group L were significantly lower than Group C. Patients in Group P and Group L had significantly higher levels of superoxide dismutase and lower levels of malondialdehyde than Group C. No significant differences were found in SPO2, ETCO2, PaCO2, Paw, HR and MAP among the three groups. The complications in Group C were significantly higher than another two groups. CONCLUSION: PGE1 can maintain adequate oxygenation in patients with low FiO2 (0.6) during OLV. Reducing FiO2 to 0.6 during OLV can decrease the levels of oxidative stress and complications after OLV. TRIAL REGISTRATION: chictr.org.cn identifier: ChiCTR1800017100.

Effect of Long-term Administration of Prostaglandin E1 on Morphologic Changes in Ductus Arteriosus.

BACKGROUND: To improve survival of patients with hypoplastic left heart syndrome, combination therapy with bilateral pulmonary artery banding and prostaglandin E1 (PGE1)-mediated ductal patency was developed as an alternative for high-risk neonates in Japan. However, the effect of long-term PGE1 administration on ductus arteriosus remains unclear. Synchrotron radiation-based X-ray phase-contrast tomography (XPCT) enables clear visualization of soft tissues at an approximate spatial resolution of 12.5 µm. We aimed to investigate morphologic changes in ductus arteriosus after long-term PGE1 infusion using XPCT. METHODS: Seventeen ductus arteriosus tissue samples from patients with hypoplastic left heart syndrome were obtained during the Norwood procedure. The median duration of lipo-prostaglandin E1 (lipo-PGE1) administration was 48 days (range, 3 to 123). Structural analysis of ductus arteriosus was performed and compared with conventional histologic analysis. RESULTS: The XPCT was successfully applied to quantitative measurements of ductal media. Significant correlation was found between the duration of lipo-PGE1 infusion and mass density of ductal media (R = 0.723, P = .001). The duration of lipo-PGE1 administration was positively correlated with elastic fiber staining (R = 0.799, P < .001) and negatively correlated with smooth muscle formation (R = -0.83, P < .001). No significant increase in intimal cushion formation was found after long-term lipo-PGE1 administration. Expression of ductus arteriosus dominant PGE2-receptor EP4 almost disappeared in specimens when lipo-PGE1 was administered over 3 days. CONCLUSIONS: Disorganized elastogenesis and little intimal cushion formation after long-term lipo-PGE1 administration suggest that ductus arteriosus remodeled to the elastic artery phenotype. Because EP4 was downregulated and ductus arteriosus exhibited elastic characteristics, the dosage of lipo-PGE1 might be decreased after a definite administration period.

Staged surgical repair for infants with interrupted aortic arch.

BACKGROUND: Interrupted aortic arch (IAA) is a rare congenital cardiac anomaly, which necessitates surgical treatment. There are several surgical strategies for corrective repair of IAA, such as one-stage repair, rapid two-stage repair and two-stage repair. Here, we reported our surgical result of staged-repair policy for the patients with IAA. METHOD: From November 2003 to July 2015, there were 14 patients (8 boys, 6 girls) with IAA treated by us. Except one teenager patient, we routinely used intravenous infusion of prostaglandin E1 for all the infant patients (n = 13) to keep adequate end organ perfusion before the first surgical intervention. Surgical repair was performed after the perfusion of end organs recovered. RESULT: Two patients (1 teenager and 1 infant with one-stage surgery) were excluded from this study. At the time of the first surgery, we did the first-stage surgery with anastomosis in between aortic arch and descending aorta, division of patent ductus arteriosus and banding of pulmonary trunk through left thoracotomy. The overall surgical survival rate of the first surgery was 100% (12/12). At the time of the second surgery, corrective repair was done under cardiopulmonary bypass through median sternotomy. The surgical survival rate of the corrective surgery was also 100%. There is no late death during follow-up for 9 years (range 4.2-15.0 years). CONCLUSION: Out of several surgical strategies for the infants with IAA, staged repair still could be a treatment option to achieve satisfied surgical result.

Management of severe complications following penile surgery for erectile dysfunction and Peyronie disease: Three case reports.

RATIONALE: Erectile dysfunction (ED) and Peyronie's disease (PD) are conditions commonly observed in andrology. Despite the surgical refinement and the technical improvement in this field, even in expert hands, detrimental consequences have been reported and it can be related to patient's comorbidities or misconduct in the postoperative period. In this article we report anecdotal cases of severe complications following penile surgery for ED and PD in high volume centers, describe the strategies adopted to treat it and discuss the options that would have helped preventing these events. PATIENTS' CONCERNS: The first case describes a patient with history of ED and PD causing penile shortening and a slight dorsal deviation of penile shaft. In the second case it is described a corporeal necrosis and urethral fistula following inflatable penile prosthesis implant. In the last case it is described the migration of reservoir into the abdomen after inflatable penile prosthesis implantation post-radical prostatectomy. DIAGNOSIS: All 3 patients were investigated with a penile doppler ultrasound with PGE1 intracorporeal injection for ED and PD diagnosis. An abdominal computed tomography scan and magnetic resonance imaging were ordered for patient of case three. INTERVENTIONS: The patients underwent different combined procedures depending on the case and including: glansectomy, penile prosthesis implantation associated with a penile elongation with double dorsal-ventral patch graft ("sliding technique"), penile urethroplasty with buccal mucosa graft, and laparotomy for reservoir removal. OUTCOMES: No further serious complications were reported after the procedures described. LESSONS: Penile surgery in patients with concomitant PD and systemic comorbidities can be at high risk of complications. As shown in this series there are possible dramatic evolution of these complications that may cause irreversible consequences to the patient. For this reason, a dedicated surgical and nursing team is necessary to reduce the chances that it happens. When this event occurs, a team trained in their management can improve the patient outcome.

The role of age in determining the effects of lipo-PGE1 infusion on immediate arterial maximal flow velocity in patients with diabetes undergoing free flap surgery for lower extremity reconstruction: A prospective observational study.

BACKGROUND: Diabetes mellitus may have a negative effect on free flap perfusion in patients undergoing reconstructive surgery. Little is known of the effects of lipo-prostaglandin E1 (lipo-PGE1) on flap blood flow in diabetes. This study investigated the effects of lipo-PGE1 on maximal blood flow velocity of the free flap arterial pedicle in patients with diabetes. METHODS: This prospective observational study assessed maximal blood flow velocity in the arterial pedicle before and 30 min after infusion of 0.4 µg/h lipo-PGE1 in 40 patients with diabetes who received a free flap for lower extremity reconstruction. Multivariate logistic regression analysis was performed to determine whether age, hemoglobin A1c concentration, duration of diabetes, and flap type were significantly associated with increased maximal blood flow velocity after lipo-PGE1 infusion or not. RESULTS: The maximal blood flow velocity of the free flap did not differ significantly before and 30 min after lipo-PGE1 infusion. Multivariate logistic regression analysis showed that age <65 years was the only independent factor associated with increased maximal blood flow velocity after lipo-PGE1 infusion (odds ratio = 5.344; p = 0.022). CONCLUSION: Assessments of all patients with diabetes undergoing free flap surgery, when age was not taken into consideration, found that lipo-PGE1 did not significantly increase the maximal blood flow velocity of the free flap arterial pedicle. However, when age was taken into consideration, lipo-PGE1 increased blood flow velocity in patients <65 years old, suggesting that age influences the effect of lipo-PGE1 on the blood flow velocity.

Prostaglandin Infusion in Neonate With Severe Coarctation of the Aorta With Closed Ductus Arteriosus-A Case Report and Review of the Literature.

We report the case of a premature newborn diagnosed with coarctation of the aorta after spontaneous closure of ductus arteriosus who was successfully managed with prostaglandin E1 infusion until surgical repair could be performed. This case, together with a review of the literature, suggests an important role for prostaglandin in the management of coarctation even in the absence of a patent ductus arteriosus. The putative mechanism for the utility of prostaglandin infusion is that it may relieve the obstruction in neonates with severe coarctation by not only opening of the ductus but, in select cases, relaxing the ductal tissue encircling the aortic isthmus region. We also found a possible dose dependence of the efficacy of the prostaglandin infusion when the ductus is closed.

Effect of alprostadil on myocardial fibrosis in rats with diabetes mellitus via TGF-ß1/Smad signaling pathway.

OBJECTIVE: To observe the influence of alprostadil on myocardial fibrosis in rats with diabetes mellitus (DM) through the transforming growth factor beta-1 (TGF-ß1)/Smad signaling pathway. MATERIALS AND METHODS: Wistar rats were employed to induce models of DM (DM group), and alprostadil treatment group (ALPR group) and control group (NC group) were set up. After successful modeling, blood and myocardial tissues were collected from rats. Next, blood glucose level, liver function, and myocardial function were detected. In addition, hematoxylin-eosin (HE) assay was performed to determine pathological changes. The enzyme-linked immunosorbent assay (ELISA) was carried out to measure serum interleukin-6 (IL-6) and cardiac function indexes such as ejection fraction (EF), Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting, which were applied to measure the gene and protein expression levels of important molecules in the proliferation and differentiation of myocardial fibroblasts [including checkpoint kinase 1 (Chek1) and alpha-smooth muscle actin (α-SMA)] and the relevant pathway TGF-ß1/Smad2. RESULTS: The blood glucose level was increased in DM group (p<0.01), suggesting that modeling is successful. The tumor necrosis factor-alpha (TNF-α), IL⁃6, and IL-1 levels were higher in DM group than in NC group. DM group had significantly elevated serum content of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and creatine kinase (CK), as well as left ventricular end-diastolic dimension (LVEDd) and left ventricular end-systolic dimension (LVESd), but it clearly decreased fractional shortening (FS) and EF in comparison with NC group. Besides, myocardial cells were orderly arranged in NC group, while myocardial fibrosis was observed in DM group. The results of RT-PCR showed that the levels of Collagen, Chek1, α-SMA, TGF-ß1, and Smad2 in myocardial fibroblasts were notably lowered in ALPR group, but evidently increased in DM group (p<0.05). According to Western blotting, there were evident decreases in the levels of TGF-ß1 and Smad2 in myocardial fibroblasts in ALPR group (p<0.05). The above results suggest that alprostadil represses the expression of the TGF-ß1/Smad2 signaling pathway and its relevant molecules, thus further suppressing the fibrosis of myocardial cells. CONCLUSIONS: Alprostadil treats myocardial fibrosis in DM rats by inhibiting the TGF-ß1/Smad2 signaling pathway.

Effectiveness and safety of intracoronary papaverine, alprostadil, and high dosages of nicorandil and adenosine triphosphate for measurement of the index of coronary microcirculatory resistance in a pig model.

BACKGROUND: Papaverine is used to induce maximal hyperemia for index of coronary microcirculatory resistance (IMR) measurement in animal experiments, although it can lead to polymorphic ventricular tachycardia and ventricular fibrillation. OBJECTIVES: This study investigated the effect of an intracoronary (IC) bolus of high adenosine triphosphate (ATP) and nicorandil doses for IMR measurement and explored the possibility of inducing maximal hyperemia with an IC alprostadil bolus. MATERIAL AND METHODS: Index of coronary microcirculatory resistance was measured in a hyperemic state induced by 7 experimental conditions in 21 pigs (IC bolus of papaverine (18 mg), ATP (40 µg, 80 µg, 160 µg, and 240 µg), and nicorandil (2 mg and 4 mg)). The 7 conditions were induced sequentially, and the average IMR was calculated. Because of the long-term hyperemic condition in the pilot experiments, the IMR was measured 1, 3, 5, 8, and 10 min after an IC bolus of alprostadil (10 µg) in another 7 pigs. RESULTS: The IMR induced by 240 µg of ATP or 4 mg of nicorandil was not significantly different from that induced by 18 mg of papaverine (both p > 0.05). A strong linear correlation was observed between IMRs with papaverine (18 mg) and nicorandil (4 mg) (R2 = 0.936, p < 0.001) and with papaverine (18 mg) and ATP (240 µg) (R2 = 0.838, p < 0.05). The IC bolus of nicorandil (4 mg) produced the smallest changes, whereas papaverine caused the most significant changes in mean blood pressure and heart rate (p < 0.05). Tachypnea and transient ST depression were more common with increasing ATP dosages (especially 240 µg). Alprostadil (5 min) yielded a significant hyperemic response but reduced baseline blood pressure by almost 40% for a long time. CONCLUSIONS: Intracoronary bolus administration of 4 mg of nicorandil was better than 18 mg of papaverine or 240 µg of ATP for induction of maximal hyperemia and IMR measurement in a pig model, whereas alprostadil was not suitable for IMR measurement.

Effect of Prostaglandin E1 Injected Into Donors in a Heterotopic Heart Transplant Model of Sprague Dawley Rats.

INTRODUCTION: Prostaglandin E1 (PGE1) administered to patients in the immediate post-transplant period has been known to reduce ischemic reperfusion injuries (IRIs), but the effect on IRI of PGE1 administered to the donor is unknown. The purpose of this study was to determine the effect on IRI of PGE1 injected into donor rats during heterotopic heart transplantation. METHODS: Genetically identical male Sprague Dawley rats with a body weight of 300-320 g at 8-9 weeks of age were used for the study. Experimental methods were the same in the control (G0, n = 6) and experimental groups (G1, n = 6), but only the donor rats in the experimental group received an intramuscular injection of PGE1 (5 µg/kg) prior to the donor surgery. On day 1 the animals were sacrificed with the removal of the transplanted heart. Histologic analysis was performed in the hematoxylin-eosin-stained slides to assess interstitial edema and neutrophil infiltration by a pathologist. RESULTS: Median times of the donor organ procurement, cold ischemia, and warm ischemia were 37, 69, and 35 minutes, respectively, in the G0 group and 38, 76.5, and 33 minutes respectively in G1 group; there were no statistical differences. Heartbeats were observed in the transplanted graft in 2 of the G0 group and 2 of G1 group immediately after heart transplantation, but in all transplanted grafts on day 1 after surgery. Histologic scores for neutrophil infiltration showed significantly lower in the G1 group than in the G0 group. CONCLUSION: PGE1 administration to donors in a rat heart transplantation model may significantly reduce IRI.

Intravenous Prostaglandin E1 Infusion for Acute Central Retinal Artery Occlusion.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of systemic prostaglandin E1 (PGE1) infusion within the first 24 hours of acute central retinal artery occlusion (CRAO). PATIENTS AND METHODS: Best corrected visual acuity (BCVA) was analyzed in a case series of six eyes from six patients (mean age: 69.33 years) with acute CRAO who were treated with twice-daily intravenous infusion of 40 µg PGE1. Therapy continued until the patient no longer experienced visual acuity improvements for 24 hours. RESULTS: Average time to presentation was 8.33 hours (range: 2 to 12 hours). The logMAR BCVA at presentation was 2.73. BCVA at the final visit 1 month after initial presentation was 1.48 (P = .025). All patients experienced vision improvement. No systemic adverse events were experienced. CONCLUSION: Intravenous PGE1 infusion resulted in significant visual improvement in patients presenting with acute CRAO and is well tolerated with few adverse effects. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:S5-S8.].

Erectile dysfunction: a global review of intracavernosal injectables.

PURPOSE: Data assessing the effectiveness of intracavernosal injections (ICIs) for the treatment of erectile dysfunction (ED) are limited. This study evaluates intracavernosal injectable therapies for ED and reviews available guidelines that inform clinical practice. METHODS: A systematic search using electronic databases (Medline, Pubmed) was performed for studies investigating injectable management strategies for ED published after 1990. Primary outcome measures were to comparatively evaluate clinical efficacy, continuation rates and adverse event profiles of each injectable agent as monotherapy or in combination. The secondary outcome measurement was to discuss available guidelines that inform clinical practice for injectable agents. RESULTS: ICIs demonstrate clinical efficacy in 54-100% of patients, early discontinuation rates of ≤ 38% and adverse events in ≤ 26%. Discontinuation rates are typically greatest within 3-6 months of commencement. Anxiety related to the initial injection occurs in approximately 65% and anxiety levels can remain high for 4 months. Approval of intracavernosal injection agents is mainly limited to alprostadil with the recent addition of aviptadil/phentolamine combination therapy in a select few geographical regions. Although combination therapies are attractive alternative options, their formulations are variable and should be standardised before widespread acceptance is achieved. CONCLUSIONS: ICIs are associated with good clinical efficacy rates, high discontinuation rates and a moderate side-effect profile. They represent an important tool in the urological armamentarium for treating ED in patients that cannot tolerate or are refractory to oral therapies.

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.

Penile rehabilitation for postprostatectomy erectile dysfunction.

BACKGROUND: Despite efforts to preserve the neurovascular bundles with nerve-sparing surgery, erectile dysfunction remains common following radical prostatectomy. Postoperative penile rehabilitation seeks to restore erectile function but results have been conflicting. OBJECTIVES: To evaluate the effects of penile rehabilitation strategies in restoring erectile function following radical prostatectomy for prostate cancer. SEARCH METHODS: We performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase), the Cochrane Library, Web of Science, clinical trial registries (ClinicalTrials.gov, International Clinical Trials Registry Platform) and a grey literature repository (Grey Literature Report) from their inception through to 3 January 2018. We also searched the reference lists of other relevant publications and abstract proceedings. We applied no language restrictions. SELECTION CRITERIA: We included randomised or quasi-randomised trials with a parallel or cross-over design. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Two review authors independently screened the literature, extracted data, assessed risk of bias and rated quality of evidence according to GRADE on a per-outcome basis. Primary outcomes were self-reported potency, erectile function measured by validated questionnaires (with potency defined as an International Index of Erectile Function (IIEF-EF) score of 19 or greater and or an IIEF-5 of score of 17 or greater) and serious adverse events. For all quality of life assessments on a continuous scale, higher values indicated better quality of life. MAIN RESULTS: We included eight randomised controlled trials with 1699 participants across three comparisons. This abstract focuses on the primary outcomes of this review only.Scheduled phosphodiesterase type 5 inhibitors (PDE5I) versus placebo or no treatmentScheduled PDE5I may have little or no effect on short-term (up to 12 months) self-reported potency (risk ratio (RR) 1.13, 95% confidence interval (CI) 0.91 to1.41; very low quality evidence), which corresponds to 47 more men with self-reported potency per 1000 (95% CI 33 fewer to 149 more) and short-term erectile function as assessed by a validated instrument (RR 1.11, 95% CI 0.80 to 1.55; very low quality evidence), which corresponds to 28 more men per 1000 (95% CI 50 fewer to 138 more), but we are very uncertain of both of these findings. Scheduled PDE5I may result in fewer serious adverse events compared to placebo (RR 0.32, 95% CI 0.11 to 0.94; low quality evidence), though this does not appear biologically plausible and may represent a chance finding. We are also very uncertain of this finding. We found no long-term (longer than 12 months) data for any of the three primary outcomes.Scheduled PDE5I versus on-demand PDE5I Daily PDE5I appears to result in little to no difference in both short-term and long-term (greater than 12 months) self-reported potency (short term: RR 0.97, 95% CI 0.62 to 1.53; long term: RR 1.00, 95% CI 0.60 to 1.67; both very low quality evidence); this corresponds to nine fewer men with self-reported short-term potency per 1000 (95% CI 119 fewer to 166 more) and zero fewer men with self-reported long-term potency per 1000 (95% CI 153 fewer to 257 more). We are very uncertain of these findings. Daily PDE5I appears to result in little to no difference in short-term and long-term erectile function (short term: RR 1.00, 95% CI 0.65 to 1.55; long term; RR 0.74, 95% CI 0.48 to 1.14; both very-low quality evidence), which corresponds to zero men with short-term erectile dysfunction per 1000 (95% CI 80 fewer to 125 more) and 119 fewer men with long-term erectile dysfunction per 1000 (95% CI 239 fewer to 64 more). We are very uncertain of these findings. Scheduled PDE5I may result in little or no effects on short-term adverse events (RR 0.69 95% CI 0.12 to 4.04; very low quality evidence), which corresponds to seven fewer men with short-term serious adverse events (95% CI 18 fewer to 64 more), but we are very uncertain of these findings. We found no long-term data for serious adverse events.Scheduled PDE5I versus scheduled intraurethral prostaglandin E1At short-term follow-up, daily PDE5I may result in little or no effect on self-reported potency (RR 1.10, 95% CI 0.79, to 1.52; very low quality evidence), which corresponds to 46 more men per 1000 (95% CI 97 fewer to 241 more). Daily PDE5I may result in a small improvement of erectile function (RR 1.64, 95% CI 0.84 to 3.20; very low quality evidence), which corresponds to 92 more men per 1000 (95% CI 23 fewer to 318 more) but we are very uncertain of both these findings. We found no long-term (longer than 12 months) data for any of the three primary outcomes.We found no evidence for any other comparisons and were unable to perform any of the preplanned subgroup analyses based on nerve-sparing approach, age or baseline erectile function. AUTHORS' CONCLUSIONS: Based on mostly very-low and some low-quality evidence, penile rehabilitation strategies consisting of scheduled PDE5I use following radical prostatectomy may not promote self-reported potency and erectile function any more than on demand use.

Grower or shower? Predictors of change in penile length from the flaccid to erect state.

In colloquial English, a "grower" is a man whose phallus expands significantly in length from the flaccid  to the erect state; a "shower" is a man whose phallus does not demonstrate such expansion. We sought to investigate various factors that might predict a man being either a grower or a shower. A retrospective review of 274 patients who underwent penile duplex Doppler ultrasound (PDDU) for erectile dysfunction between 2011 and 2013 was performed. Penile length was measured, both in the flaccid state prior to intracavernosal injection (ICI) of a vasodilating agent (prostaglandin E1), and at peak erection during PDDU. The collected data included patient demographics, vascular, and anatomic parameters. The median change in penile length from flaccid to erect state was 4.0 cm (1.0-7.0), and was used as a cut-off value defining a grower (≥4.0 cm) or a shower (4.0 cm). A total of 73 men (26%) fit the definition of a grower (mean change in length of 5.3 cm [SD 0.5]) and 205 (74%) were showers (mean change in length of 3.1 cm [SD 0.9]). There were no differences between the groups with regards to race, smoking history, co-morbidities, erectile function, flaccid penile length, degree of penile rigidity after ICI, or PDDU findings. Growers were significantly younger (mean age 47.5 vs. 55.9 years, p < 0.001), single (37% vs. 23%, p = 0.031), received less vasodilator dose (10.3 mcg vs. 11.0 mcg, p = 0.038) and had a larger erect phallus (15.5 cm vs. 13.1 cm, p < 0.001). On multivariate analysis, only younger age was significantly predictive of being a grower (p < 0.001). These results suggest that younger age and single status could be predictors of a man being a grower, rather than a shower. Larger, multicultural and multinational studies are needed to confirm these results.