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.

Clinical effectiveness of postoperative prostaglandin E1 administration in reducing flap necrosis following microsurgical reconstruction.

BACKGROUND: Extensive experimental evidence has suggested the potential efficacy of prostaglandin E1 (PGE1) in enhancing flap survival, leading to its widespread empirical use following free flap operation. However, the translation of these experimental findings into clinical benefits remains uncertain. This study aimed to assess the clinical effectiveness of postoperative PGE1 administration on the outcomes of microsurgical reconstruction. METHODS: A retrospective review was conducted for patients who underwent free flap-based reconstruction between September 2020 and November 2022, dividing into two cohorts. For all consecutive cases conducted during the formal half, PGE1 was administered for postoperative 7 days (PGE1 cohort), and for those during the latter, PGE1 was not given (non-PGE1 cohort). The profiles of perfusion-related complications (PRC) were compared between the two cohorts. Further analyses after propensity-score matching were performed. RESULTS: In total, 274 cases were analyzed, consisting of 142 in PGE1 and 132 in non-PGE1 cohort. Baseline characteristics were similar between the two cohorts, except for higher rates of comorbidities and chronic wound-related defects in the PGE1 cohort. Overall PRC developed in 37 cases (13.5%), including 6 (2.1%) total loss and 38 (10.2%) partial necrosis. Compared to the control, the PGE1 cohort exhibited significantly lower rates of overall PRC and partial flap necrosis. This difference remained significant on multivariable analyses. The rate of total flap loss did not differ between the cohorts. Consistent associations were observed in the propensity-score matching analysis. CONCLUSION: Postoperative administration of PGE1 appears to be associated with reduced risks for the development of partial flap necrosis.

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).

Standardizing Prostaglandin Initiation in Prenatally Diagnosed Ductal-Dependent Neonates; A Quality Initiative.

Prostaglandin E1 (PGE) is used in patients with ductal-dependent congenital heart disease (CHD). Side effects of apnea and fever are often dose dependent and occur within 48 h after initiation. We initiated a standardized approach to PGE initiation after our institution recognized a high incidence of side effects and a wide variety of starting doses of PGE. Neonates with prenatally diagnosed ductal-dependent CHD were identified, started on a standardized protocol that started PGE at 0.01 mcg/kg/min, and evaluated for PGE related side effects. Compliance, outcomes and dose adjustments during the first 48 h post-PGE initiation were evaluated. Fifty patients were identified (25 pre-intervention; 25 post-intervention). After intervention, compliance with the protocol was 96%, and apnea or fever occurred in 28% (compared to 63% pre-intervention, p = 0.015). Dose adjustments (either increase or decrease) prior to cardiac surgery were similar in both cohorts (60%, 52%, p = 0.569). There were no mortalities or emergent procedures performed due to ductus arteriosus closure. Standardizing a protocol for initiating PGE in prenatally diagnosed ductal-dependent CHD was successful and reduced the incidence of apnea, fever, and sepsis evaluations. A starting dose of 0.01 mcg/kg/min did not cause increased adverse effects.

The long-term efficacy of transoral incisionless fundoplication with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease.

BACKGROUND: To evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease (GERD). METHODS: A total of 16 patients with proton pump inhibitor-dependent gastroesophageal reflux disease had undergone TIF by MUSE in Shanghai General Hospital （Shanghai, China）from March 2017 to December 2018. Patients were followed up at 6 months, and the GERD-health-related quality of life (GERD-HRQL) questionnaire score, the GERD questionnaire (GERD-Q) score, high-resolution esophageal manometry (HREM) and 24 h esophageal pH parameters, the Hill grade of the gastroesophageal flap valve (GEFV) and daily Proton pump inhibitor (PPI) consumption before and after procedure were compared. Patients also were followed up at 3 years and 5 years using a structured questionnaire via phone which evaluated symptoms of reflux, dose of PPI medication and side effects. RESULTS: Follow-up data were collected from 13 patients, ranging from 38 to 63 months, 53 months on average. 10/13 patients reported symptomatic improvement and daily PPI consumption was stopped or halved in 11/13. After procedure, the mean scores of GERD-HRQL and GERD-Q were significantly increased. The mean DeMeester score, the mean acid exposure time percentage and the mean number of acid reflux episodes were significantly lower. The mean rest pressure at lower esophageal sphincter (LES) had no significant difference. CONCLUSION: TIF by MUSE has significant efficacy in the treatment of PPI-dependent GERD, which can improve symptoms and life quality of patients, and reduce the acid exposure time for long-term. Chictr.org.cn. TRIAL REGISTRATION: ChiCTR2000034350.

Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials.

OBJECTIVES: In the anifrolumab systemic lupus erythematosus (SLE) trial programme, there was one trial (TULIP-1) in which BILAG-based Composite Lupus Assessment (BICLA) responses favoured anifrolumab over placebo, but the SLE Responder Index (SRI(4)) treatment difference was not significant. We investigated the degree of concordance between BICLA and SRI(4) across anifrolumab trials in order to better understand drivers of discrepant SLE trial results. METHODS: TULIP-1, TULIP-2 (both phase 3) and MUSE (phase 2b) were randomised, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks, 48 weeks; TULIP-1/TULIP-2: n=180; MUSE: n=99) or placebo (TULIP-1: n=184, TULIP-2: n=182; MUSE: n=102). Week 52 BICLA and SRI(4) outcomes were assessed for each patient. RESULTS: Most patients (78%-85%) had concordant BICLA and SRI(4) outcomes (Cohen's Kappa 0.6-0.7, nominal p<0.001). Dual BICLA/SRI(4) response rates favoured anifrolumab over placebo in TULIP-1, TULIP-2 and MUSE (all nominal p≤0.004). A discordant TULIP-1 BICLA non-responder/SRI(4) responder subgroup was identified (40/364, 11% of TULIP-1 population), comprising more patients receiving placebo (n=28) than anifrolumab (n=12). In this subgroup, placebo-treated patients had lower baseline disease activity, joint counts and glucocorticoid tapering rates, and more placebo-treated patients had arthritis response than anifrolumab-treated patients. CONCLUSIONS: Across trials, most patients had concordant BICLA/SRI(4) outcomes and dual BICLA/SRI(4) responses favoured anifrolumab. A BICLA non-responder/SRI(4) responder subgroup was identified where imbalances of key factors driving the BICLA/SRI(4) discordance (disease activity, glucocorticoid taper) disproportionately favoured the TULIP-1 placebo group. Careful attention to baseline disease activity and monitoring glucocorticoid taper variation will be essential in future SLE trials. TRIAL REGISTRATION NUMBERS: NCT02446912 and NCT02446899.

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.

Effects of Alprostadil Combined with Edaravone on Inflammation, Oxidative Stress and Pulmonary Function in Patients with Traumatic Hemorrhagic Shock.

The study aimed to explore the roles of alprostadil combined with edaravone in inflammation, oxidative stress and Pulmonary function in patients with traumatic hemorrhagic shock (HS). 80 patients with traumatic HS treated in Feicheng Hospital Affiliated to Shandong First Medical University and Tai'an City Central Hospital from January 2018 to January 2022 were enrolled and divided into observation group (n=40) and control group (n=40) according to the randomized control method.  Patients in the control group were given alprostadil alone (5 g alprostadil + 10 mL normal saline) in addition to conventional treatment, while those in the observation group received edaravone (30 mg edaravone + 250 mL normal saline) on the basis of treatment in the control group. The patients in both groups were treated via intravenous infusion once a day for 5 days. 24 hours (h) after resuscitation, venous blood were collected to detect serum biochemical indicators such as blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Enzyme-linked immunosorbent assay (ELISA) was conducted to determine serum inflammatory factors. Lung lavage fluid was collected to examine pulmonaryfunction indicators such as myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9) activity and to observe the oxygenation index (OI). Blood pressure was measured at admission and 24 h after surgery. The observation group had significantly lowered serum BUN, AST and ALT (p<0.05), the content of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) as well as oxidative stress indexes like superoxide dismutase (SOD) and malondialdehyde (MDA) (p<0.05) and pulmonary function indicators (p<0.05) but overtly increased content of SOD and OI. Furthermore, the blood pressure in the observation group dropped to 30 mmHg at admission and rose to the normal range. Alprostadil combined with edaravone effectively reduces inflammatory factors and improves oxidative stress and pulmonary function in patients with traumatic HS, whose efficacy is significantly better than that of alprostadil alone.

Anti-inflammatory potential of Lactobacillus reuteri LM1071 via eicosanoid regulation in LPS-stimulated RAW264.7 cells.

AIMS: To investigate anti-inflammatory effects of Lactobacillus reuteri LM1071 in lipopolysaccharides (LPS)-induced inflammation RAW264.7 cells. METHODS AND RESULTS: To evaluate anti-inflammatory activities of L. reuteri LM1071, LPS-stimulated RAW264.7 cells were used. Gene expression levels of eight immune-associated genes including IL-1ß, IL-6 and TNF-α and protein production levels of COX-1 and COX-2 were analysed. Moreover, the production of eicosanoids as important biomarkers for anti-inflammation was determined. CONCLUSIONS: The current study demonstrates that L. reuteri LM1071 has anti-inflammatory potential by inhibiting the production of inflammation mediators such as NO, eicosanoids such as PGE1 & PGE2, pro-inflammatory cytokines and COX proteins. It can also enhance the production of inflammatory associated genes such as IL-11, BMP4, LEFTY2 and EET metabolite. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus reuteri is one of the crucial bacteria for food fermentation. It can be found in the gastrointestinal system of human and animals. Several studies have shown that L. reuteri has valuable effects on host health. The current study firstly demonstrated that L. reuteri has a beneficial effect on the inflammation containing the variation of eicosanoids (PGE1 and PGE2) which are one of the most important biomarkers and moreover eicosanoid-associated genes as well as proteins (COX-2).

Transoral incisionless fundoplication with Medigus ultrasonic surgical endostapler (MUSE) for the treatment of gastro-esophageal reflux disease: outcomes up to 3 years.

BACKGROUND: Transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) is a new intervention for treatment of gastro-esophageal reflux disease (GERD). We aimed at assessing the clinical, functional, and endoscopic effects of TIF by MUSE. METHODS: Forty-six patients underwent TIF. Proton pump inhibitor (PPI) consumption, GERD-health-related quality of life (HRQL) and reflux symptom index (RSI) questionnaires, upper gastrointestinal (GI) endoscopy, esophageal 24-h pH-impedance recording, and high-resolution manometry (HRM) were done before TIF and scheduled 6 and 12 months later (HRM only at 6-month). PPI consumption and symptoms were then assessed yearly. Data up to 3 years are reported in this study (PP- and ITT-analysis). RESULTS: TIF was successfully performed in 45/46 patients; in one patient esophageal intubation was impossible. Perforation occurred in two cases. One patient required surgery within 6 months. Clinical follow-up was available for 42 patients at 6 months and 1 year, 35 patients at 2 years, and 31 patients at 3 years. At 1, 2, and 3 years, PPI consumption was stopped, respectively, in 64.3%, 62.9%, and 74.2% of cases (ITT-analysis: 58.7%, 56.4%, and 65.7%). GERD-HRQL and RSI scores decreased at least 50%, respectively, in 71.5% and 76.2%, 71.4% and 68.6%, and 67.7% of cases (ITT-analysis: 65.2% and 69.6%, 64.1% and 61.5%, and 60%). A significant improvement of both scores was observed up to 3 years. 6-month and 1-year functional follow-up were possible in 31 and 20 patients. HRM showed significant increase of the median lower esophageal sphincter length and rate of peristaltic waves. Esophageal pH-impedance recording found significantly fewer acid, proximal and total refluxes, and percentage of esophageal pH < 4 total time at 6 months, but not at 1 year. CONCLUSION: TIF by MUSE significantly improved symptoms and PPIs consumption up to 3 years. However, esophagitis still persisted in one-third of cases at 1 year and functional improvement at 6 months was not confirmed at 1 year. Severe complications requiring surgery occurred in two cases. CLINICALTRIALS: GOV: ID: NCT03669874.

Lipid microsphere-coated PGE1 improves peritoneal transport and reduces inflammation in peritoneal dialysis: A randomized clinical pilot trial.

OBJECTIVE: To evaluate the effects of lipid microspheres coated with prostaglandin E1 (lipo-PGE1) on peritoneal transport function and inflammation in patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: In total, 89 patients were randomly allocated to the lipo-PGE1 and control groups. All the patients received conventional treatment, and those in the lipo-PGE1 group received lipo-PGE1 intravenously for 2 weeks. The levels of ß2-microglobulin (ß2-MG), cystatin C, albumin, urea, creatinine, interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), and high-sensitivity C-reactive protein (hs-CRP) were measured before and at 1 and 2 weeks after treatment. RESULTS: In the lipo-PGE1 group, the peritoneal clearance rates of ß2-MG, cystatin C, and albumin were significantly increased comparing with pre-treatment values, and the IL-6 appearance rate (AR) in the peritoneal dialysate and the serum levels of IL-6 and hs-CRP were markedly decreased (p < 0.05). The lipo-PGE1 group had significantly higher peritoneal clearance rates of ß2-MG and cystatin C and lower IL-6 AR in the peritoneal dialysate than the control group (p < 0.05). CONCLUSIONS: Lipid microspheres coated with prostaglandin E1 may increase the peritoneal clearance of moderately sized molecules and macromolecules with insignificant effect on the clearance of small molecules. The reduction in IL-6 level following treatment with lipo-PGE1 may alleviate inflammation.

The Influence of Prostaglandin E1 and Use of Inhibitor Percentage on the Correlation between the Multiplate and VerifyNow in Patients on Dual Antiplatelet Therapy.

Platelet function tests (PFT), such as the Multiple Electrode Analyzer (Multiplate) and VerifyNow, show little concordance in patients using antiplatelet drugs. A major difference between these tests is the use of prostaglandin E1 (PGE1) to inhibit P2Y1-platelet-receptor activation in VerifyNow and is proposed to be of influence in the discrepancy between these tests. We aimed to investigate whether the presence of PGE1 could provide an explanation for the moderate correlation and concordance between Multiplate and VerifyNow by adding PGE1 to the Multiplate ADP assay, also known as the ADP-high sensitivity (ADP-HS) assay. We also aimed to investigate whether the difference in baseline platelet function as measured by the VerifyNow and Multiplate could (partly) explain the moderate correlation between the tests, by plotting ADP assay results against baseline function as measured by the corresponding device, which is expressed as the 'inhibitor percentage.' Fifty-one patients who underwent percutaneous coronary intervention (PCI) received dual antiplatelet therapy and were considered to have a high risk of ischemic or bleeding complications were included. The addition of 20 µl PGE1 in the Multiplate resulted in a significant reduction in Arbitrary Aggregation Units, but did not improve correlation with the VerifyNow. The correlation between VerifyNow and Multiplate inhibitor percentage was moderate. Based on these results, we concluded that neither PGE1 nor the calculation of the inhibitor percentage greatly influenced the correlation between PFTs.

Elective Non-Urgent Balloon-Atrial Septostomy in Infants with d-Transposition of the Great Arteries Does Not Eliminate the Need for PGE1 Therapy at the Time of Arterial Switch Operation.

Once a mainstay in the treatment of neonates with d-transposition of the great arteries (d-TGA), the application of balloon atrial septostomy (BAS) in the d-TGA population has become more selective. Currently, there is no clear evidence for or against a selective BAS strategy. The aims of this single-center retrospective study were to determine the incidence of BAS in the neonatal d-TGA population in the current era, to measure the rate of procedural success, and to compare the outcomes and complication rates of patients who underwent BAS to those who underwent neonatal ASO alone. Between 2012 and 2018, 147 patients with d-TGA underwent initial medical management and ASO, 73 of which underwent BAS. The percentage of patients that underwent BAS decreased from 73 to 33% over the study time period. In patients with d-TGA with intact ventricular septum, 33% of patients remained off of PGE1 at the time of surgery regardless of BAS. In d-TGA with ventricular septal defect, 85.7% of those that underwent BAS and 54.1% of those who did not remained off of PGE1 at the time of surgery, however, this difference did not reach statistical significance. In this single institution retrospective cohort of patients with d-TGA, the performance of a technically successful balloon atrial septostomy did not eliminate the need for PGE1 therapy at the time of definitive ASO. This was true regardless of the presence or absence of a ventricular septal defect.

Effect of hyperbaric oxygen combined with alprostadil in the treatment of elderly diabetic nephropathy and effects on serum miR-126 and miR-342 levels.

This study aims to investigate the effect of hyperbaric oxygen combined with alprostadil in the treatment of elderly diabetic nephropathy (DN) and its effect on serum miR-126 and miR-342 levels. The total effective rate of the study group was 91.53% after treatment, which was higher than that (74.58%) of the control group (p<0.05); the levels of UAER, Scr, BUN and HbA1c, FPG, 2h PG were lowered in the two groups after treatment, and the levels of these indexes were lower in the study group than those in the control group (p<0.05); the levels of vWF, ET-1, CD8+, miR-342 were lowered after treatment for the two groups, and the levels of these indexes were lower in the study group than those in the control group; the levels of NO, CD3+, CD4+ and miR-126 were increased after treatment and the levels were higher in the study group than those in the control group (p<0.05). The application of hyperbaric oxygen combined with alprostadil in the treatment of elderly DN patients can improve renal function, lower blood glucose, improve vascular endothelial function and immune function, adjust serum miR-126 and miR-342 levels, thereby increasing curative effect.

Pharmacological treatment for Buerger's disease.

BACKGROUND: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The aetiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularisation to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.This is an update of the review first published in 2016. OBJECTIVES: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 15 October 2019. The review authors searched LILACS, ISRCTN, Australian New Zealand Clinical Trials Registry, EU Clinical Trials Register, clincialtrials.gov and the OpenGrey Database to 5 January 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. DATA COLLECTION AND ANALYSIS: Two review authors, independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: No new studies were identified for this update. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; 1 study; moderate-certainty evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; 1 study; moderate-certainty evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; 1 study; moderate-certainty evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; 2 studies; I² = 0%; very low-certainty evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; 1 study; low-certainty evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; 1 study; moderate-certainty evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; 1 study; moderate-certainty evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; 1 study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; 1 study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low-certainty evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the certainty of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information (for example regarding baseline tobacco exposure). AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Very low and low-certainty evidence suggests there is no clear difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very low-certainty evidence suggests there is no clear difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. Further well designed RCTs assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.

Tricuspid atresia: Where are we now?

Tricuspid atresia (TA) is a complex congenital heart disease that presents with cyanosis in the neonatal period. It is invariably fatal if left untreated and requires multiple stages of palliation. Early recognition and timely surgical intervention are therefore pivotal in the management of these infants. This literature review considers the pathophysiology, presentation, investigations, and classification of TA. Moreover, it discusses the evidence upon which the latest medical and surgical treatments are based, as well as numerous recent case reports. Further work is needed to elucidate the etiology of TA, clarify the role of pharmacotherapy, and optimize the surgical management that these patients receive.

The Role of Hormones and Trophic Factors as Components of Preservation Solutions in Protection of Renal Function before Transplantation: A Review of the Literature.

Transplantation is currently a routine method for treating end-stage organ failure. In recent years, there has been some progress in the development of an optimal composition of organ preservation solutions, improving the vital functions of the organ and allowing to extend its storage period until implantation into the recipient. Optimizations are mostly based on commercial solutions, routinely used to store grafts intended for transplantation. The paper reviews hormones with a potential nephroprotective effect, which were used to modify the composition of renal perfusion and preservation solutions. Their effectiveness as ingredients of preservation solutions was analysed based on a literature review. Hormones and trophic factors are innovative preservation solution supplements. They have a pleiotropic effect and affect normal renal function. The expression of receptors for melatonin, prolactin, thyrotropin, corticotropin, prostaglandin E1 and trophic factors was confirmed in the kidneys, which suggests that they are a promising therapeutic target for renal IR (ischemia-reperfusion) injury. They can have anti-inflammatory, antioxidant and anti-apoptotic effects, limiting IR injury.

Sexual dysfunction in men after high energy pelvic fractures: Narrative review of targeted literature.

Pelvic fractures represents high energy trauma with associated other organ injuries including intra-abdominal injuries, haemorrhage and extremity injuries. Anatomical location of genitourinary structures makes them vulnerable to injury with pelvic fracture. Incidence of sexual dysfunction varies in literature with 5% incidence of dysfunction in patients without urethral injury and 42% with urethral injuries. Hence in pelvic fracture, erectile dysfunction may be due to neurogenic, vascular, corporal and psychogenic injury. In this narrative review of targeted English literature from all level of evidences, which is written and supervised by experienced specialized orthopaedic, trauma and urology surgeons who were among the pioneers of conducting pelvis fracture management workshops in the country, we aim to describe the mechanism that can lead to erectile dysfunction after pelvic fracture, assessment principles, decision-making and preoperative planning and indications of operative managements.

Protective Effect of Alprostadil on Acute Pancreatitis in Rats via Inhibiting Janus Kinase 2 (JAK2)/STAT3 Signal Transduction Pathway.

BACKGROUND Alprostadil can inhibit inflammation and reduce inflammation-related injury in many inflammatory diseases. However, the anti-inflammatory effect of alprostadil in decreasing acute pancreatitis (AP) injury remains unknow. This study aimed to investigate the possible protective effects and mechanism of alprostadil against AP in rats. MATERIAL AND METHODS Forty healthy Sprague­Dawley rats were randomly divided into a control group, an AP group, an AP-alprostadil group, an AP-AG490 group, and an AP-(alprostadil+AG490) group. An animal model of acute pancreatitis was established. The pathological changes of the pancreases in each group were observed. We assessed levels of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO), as well as serum IL-1ß, IL-6, IL-10, and TNF-alpha. TUNEL assay was used to detect apoptosis of pancreatic cells. The proteins p-Jak2 and p-Stat3 were investigated by Western blot. RESULTS Compared with the control group, pancreatic pathological score, pancreatic apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha levels were significantly higher in the AP group, and SOD levels were significantly decreased. Compared with the AP group, after treatment with alprostadil, AG490, and alprostadil+AG490, respectively, the pancreatic pathological score, apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha were significantly decreased in AP rats, while SOD levels were significantly increased. The protein levels of p-JAK2 and p-STAT3 were significantly upregulated in the AP group compared with the control group, and the protein levels of p-JAK2 and p-STAT3 after treatment with alprostadil, AG490, and alprostadil+AG490 were significantly decreased, and the effect of alprostadil+AG490 was the strongest. CONCLUSIONS Alprostadil can reduce pancreatic tissue damage, delay pancreatic cell apoptosis, and reduce inflammation and anti-oxidative stress by inhibiting the JAK2/STAT3 signal pathway, thus protecting the pancreas.