Vascular Causes Research Articles

Downstream or upstream administration of P2Y12 receptor blockers in non-ST elevated acute coronary syndromes: study protocol for a randomized controlled trial

BackgroundThe optimal timing to administer a P2Y12 inhibitor in patients presenting with a non-ST elevation acute coronary syndrome remains a topic of debate. Pretreatment with ticagrelor before coronary anatomy is known as a widely adopted strategy. However, there is poor evidence on how this compares with administration of a P2Y12 inhibitor after defining coronary anatomy (i.e., downstream administration). Moreover, there are limited head-to-head comparisons of the two P2Y12 inhibitors—ticagrelor and prasugrel—currently recommended by the guidelines.Study designDUBIUS is a phase 4, multicenter, parallel-group, double randomized study conducted in NSTE-ACS patients designed to compare a pretreatment strategy (including only ticagrelor) versus a downstream strategy (including prasugrel or ticagrelor) and to compare downstream prasugrel with downstream ticagrelor. A total of 2520 patients will be randomly assigned to pretreatment with ticagrelor or to no pretreatment. The PCI group of the downstream arm will be further randomized to receive prasugrel or ticagrelor. The two primary hypotheses are that the downstream strategy is superior to the upstream strategy and that downstream ticagrelor is non-inferior to downstream prasugrel, both measured by the incidence of a composite efficacy and safety endpoint of death from vascular causes, non-fatal MI, or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4, and 5 bleedings.ConclusionsThe DUBIUS study will provide important evidence related to the benefits and risks of pretreatment with ticagrelor compared with a strategy of no pretreatment. Moreover, the clinical impact of using downstream ticagrelor compared with downstream prasugrel will be assessed.Trial registrationClinicalTrials.gov NCT02618837. Registered on 1 December 2015.

The association between systemic autoimmune disorders and epilepsy and its clinical implications.

Systemic autoimmune disorders occur more frequently in patients with epilepsy than in the general population, suggesting shared disease mechanisms. The risk of epilepsy is elevated across the spectrum of systemic autoimmune disorders but is highest in systemic lupus erythematosus and type 1 diabetes mellitus. Vascular and metabolic factors are the most important mediators between systemic autoimmune disorders and epilepsy. Systemic immune dysfunction can also affect neuronal excitability, not only through innate immune activation and blood-brain barrier dysfunction in most epilepsies but also adaptive immunity in autoimmune encephalitis. The presence of systemic autoimmune disorders in subjects with acute seizures warrants evaluation for infectious, vascular, toxic and metabolic causes of acute symptomatic seizures, but clinical signs of autoimmune encephalitis should not be missed. Immunosuppressive medications may have antiseizure properties and trigger certain drug interactions with antiseizure treatments. A better understanding of mechanisms underlying the co-existence of epilepsy and systemic autoimmune disorders is needed to guide new antiseizure and anti-epileptogenic treatments. This review aims to summarize the epidemiological evidence for systemic autoimmune disorders as comorbidities of epilepsy, explore potential immune and non-immune mechanisms, and provide practical implications on diagnostic and therapeutic approach to epilepsy in those with comorbid systemic autoimmune disorders.

Stroke patients care by the Senegal-National Emergency Medical Services: retrospective study over 18 months

ntroduction: Stroke according to the WHO (World Health Organization) is a sudden deficit of focal brain function with no apparent cause other than a vascular cause. It is a major public health problem. It is the first cause of motor disability, second cause of cognitive disability and third cause of mortality in the world. Material and method: It is a retrospective and descriptive study of a period of 18 months (January 1, 2016 to October 30, 2017) conducted in the national Emergency Medical Services of Dakar (Senegal). According to our study criteria, 343 patients were collected. Results: The mean age of the patients was 64.2 years (extremes of 17 and 104 years). Men represented 54.22% (sex ratio M/W 1.8). Dakar represented the main provenance of our patients (79.30%). Hypertension was the main risk factor (50%). Acute headaches were the main warning sign (13.41%). An echocardiography was performed in 59 patients; complete tachyarrhythmia by atrial fibrillation represented 30% of the ECG. The CT-scan was performed for 201 patients (61% of ischemic stroke, 37.5% hemorrhagic and 1.5% of transient ischemic attack). The medevac represented 53.93%. Transportation was made essentially by the emergency medical services; home interventions were the most represented. The mean time for intervention by the emergency medical services was 134.71 minutes. Fann Hospital was the main host structure (45.49%). The care (of the emergency medical services) included, among others, intubation (4.8%), monitoring, oxygen therapy, urinary catheter and medical treatment. We noticed 20.40% of deaths in our series, due essentially to neurological complications. Conclusion: Stroke is a major public health problem. Difficulties are sometimes encountered in the care and the research of an appropriate host structure. The purpose of the pre-hospital care is to intervene as soon as possible while making a clinic diagnosis by performing forthwith a brain CT-scan in order to optimize the care and improve the prognostic of stroke patients.

Interdisciplinary approach to ischemic stroke – a case report

The definition of “stroke” by the World Health Organization describes a clinical syndrome characterized by a rapid onset of focal or global cerebral deficit, lasting more than 24 h or leading to death, due to a vascular ischemic cause. Ischemic stroke (IS) usually occurs when the blood supply to an area of the brain is interrupted and accounts for the majority of strokes. It includes cryptogenic, lacunae, and thromboembolic strokes. The most common risk factors are arterial hypertension, diabetes mellitus, obesity and cigarette smoking. About 87% of all strokes are ischemic strokes. Globally, stroke is a leading cause of death and disability and the economic costs of treatment and post-stroke care are substantial. Bulgaria is among the first in morbidity and mortality from cerebrovascular diseases. We present a case of a 36-year-old patient admitted to First Neurology Clinic at the St. Marina University Hospital, Varna, Bulgaria with complaints of tingling in the hands, more on the right hand. This case was a diagnostic challenge, which involved doctors from different specialties.

Abstract 13474: Rivaroxaban Reduces Major Cardiovascular and Limb Events in Patients With the High-risk Triad of Chronic Kidney Disease, Peripheral Artery Disease and Recent Lower Extremity Revascularization: Insights From VOYAGER PAD

Introduction: Chronic kidney disease (CKD) is common among patients undergoing lower extremity revascularization (LER) for peripheral artery disease (PAD) and identifies a population at high risk for adverse outcomes. The VOYAGER PAD trial demonstrated the efficacy of rivaroxaban in PAD patients after LER on a composite of cardiovascular (CV) and limb ischemic events (HR 0.85 vs placebo, 95% CI 0.76-0.96; p=0.009); this analysis examines the prespecified subgroup of patients with CKD. Methods: VOYAGER PAD (NCT02504216) was a double-blind, placebo-controlled trial which randomized PAD patients with recent LER to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. The primary endpoint was a composite of acute limb ischemia, major amputation for vascular cause, myocardial infarction, ischemic stroke or CV death. The primary safety endpoint was TIMI major bleeding. Analysis of the intention-to-treat population utilized Kaplan Meier estimates and Cox proportional-hazards models. Results: Among 6319 VOYAGER patients with baseline estimated glomerular filtration rate (eGFR), 21% were <60 (mostly CKD stage 3) and 79% were ≥60 ml/min/1.73m 2 . During 28-month (median) follow up, patients with CKD had a higher rate of major CV and limb events: placebo group 10.0 events/100 patient-years (95% CI 8.5, 11.8) for eGFR <60 vs 7.4 (95% CI 6.7, 8.2) for eGFR ≥60. Rivaroxaban reduced primary outcome events with no heterogeneity by eGFR category (Figure, p for interaction 0.62). Acute limb ischemia and major amputation were significantly reduced among patients with eGFR<60 (HR 0.55, 95% CI 0.36, 0.86) as well as ≥60 (HR 0.77, 95% CI 0.63, 0.94). TIMI major bleeding was numerically more frequent among patients with CKD with no heterogeneity by treatment group (Figure, p for interaction 0.37). Conclusions: Rivaroxaban reduced major CV and limb events in patients with PAD undergoing LER, including those with CKD, a particularly high-risk population.

Early Patient Experiences of Primary Above-the-Knee Amputation From Vascular Etiologies: A Phenomenological Study.

The aim of this study was to explore the different meanings of the experience of lower-limb amputation due to vascular causes in the time period from the fifth to twelfth week post-amputation. A phenomenological study involving semi-structured interviews was carried out. Data collection took place in a Public Hospital in Spain and included a convenience sample of 20 patients who had undergone amputation. The study highlighted patients' fears related to mobility, pain, dependence, and autonomy. Moreover, patients experience of the rehabilitation process and resources for adaptation were described as well as all the changes related to the social environment. The figure of a nurse was considered essential after amputation by the patients. This study provides a deep understanding of their experiences at the immediate time after amputation considering patients demographical associations and the etiology of the vascular pathology. This could be the starting point to understand patients' immediate needs upon discharge.

Barriers to accessing and providing rehabilitation after a lower limb amputation in Sierra Leone – a multidisciplinary patient and service provider perspective

Purpose The primary aim was to explore the perceived barriers that lower limb amputees and service providers face when accessing or providing rehabilitation services. The secondary aim was to describe the lower limb amputations performed in public hospitals in the Western Area of Sierra Leone in 2018. Materials and methods A mixed methodology was employed, involving the collection of amputation data from surgical logbooks and interviews with amputees (n = 10) and group discussion and interviews with service providers (n = 11). Results Of the 37 primary lower limb amputations (49% men, 51% women; median age 56 years; 62% transtibial and 35% transfemoral amputations) 86% were for diabetic and vascular causes. Barriers to accessing services included poor transportation access, high service fees, rural living, gender and a lack of government support. Insufficient funding and supplies, skilled staff shortages and a lack of local training programmes were frequently reported barriers to providing rehabilitation services. Conclusions A low prioritisation means rehabilitation services are underfunded, resulting in numerous barriers to both accessing and providing amputee rehabilitation services. Subsidised services and an outreach programme may improve access for patients. Increased funding and local training programmes are needed to improve service delivery. Implications for Rehabilitation Comprehensive and accessible amputee rehabilitation services can enable people with amputations to regain their independence and aid their participation in their community and workplace. There are numerous barriers to both accessing and providing amputee rehabilitation services in the Western Area, Sierra Leone, chiefly financial. We recommend a revised effort by the Sierra Leonean government to implement the progressive policies on disability they have already adopted into law, which will aid the improvement of amputee rehabilitation services. New education and training programmes for all levels of prosthetic and orthotic professions are needed to secure the future of prosthetics and orthotics in Sierra Leone.

Prevalence, Surgical Management, and Audiologic Impact of Sigmoid Sinus Dehiscence Causing Pulsatile Tinnitus.

To evaluate the prevalence, surgical management, and audiologic impact of pulsatile tinnitus caused by sigmoid sinus dehiscence. Retrospective chart review at a tertiary care hospital. Adults with unilateral pulsatile tinnitus attributable to sigmoid sinus dehiscence who underwent resurfacing between January 2010 and January 2020. Transmastoid sigmoid resurfacing. Resolution of pulsatile tinnitus; audiologic outcomes; complications; tinnitus etiologies. Nineteen patients (89.4% women) had surgery for suspected sigmoid sinus dehiscence. The mean dehiscence size was 6.1 mm (range, 1-10.7 mm). Eight patients had concurrent sigmoid sinus diverticulum and one patient also had jugular bulb dehiscence. Only two patients (10.5%) had the defect identified by radiology. Low-frequency pure-tone average, measured at frequencies of 250 and 500 Hz, showed a significant median improvement of 8.8 dB following resurfacing (18.8 dB versus 10.0 dB, p = 0.02). The majority of patients had complete resolution of pulsatile tinnitus (16/19, 84.2%). Of those without complete resolution, two patients had partial response and one patient had no improvement. There were no significant complications. Of 41 consecutively tracked patients with a pulsatile tinnitus chief complaint, sigmoid pathology represented 32% of cases. Sigmoid sinus dehiscence represents a common vascular cause of pulsatile tinnitus that, if properly assessed, may be amenable to surgical intervention. Sigmoid sinus resurfacing is safe, does not require decompression, and may improve low-frequency hearing. Radiographic findings of dehiscence are often overlooked without a high index of clinical suspicion. Its relationship with transverse sinus pathology and idiopathic intracranial hypertension remain unclear.

Liver disease in the older child.

Liver disease in children tends to present either as: (i) an acute hepatitis with or without jaundice; (ii) incidental finding of abnormal liver function tests; or (iii) from a complication of portal hypertension with either haematemesis and/or incidental splenomegaly. Acute hepatitis may result from acute infection, prescribed or other drugs, ischaemia or vascular causes, autoimmune hepatitis, or idiopathic liver failure. Non-alcoholic fatty liver disease is now the most likely reason for abnormal liver function tests but medications, metabolic disease, cholangiopathy and non-liver causes should be considered. Autoimmune hepatitis and alpha-1-antitrypsin deficiency are the most likely causes of insidious liver disease. An international normalised ratio uncorrected by vitamin K reflects the severity of liver synthetic dysfunction, but not propensity to bleed. Creatine kinase helps to differentiate muscle from liver disease in patients with raised transaminases. Doppler ultrasound of hepatic vasculature is useful when assessing splenomegaly to differentiate extra-hepatic portal hypertension from inherent liver disease.

Pleiotropic effects of ticagrelor on microRNA expression in acute coronary syndrome on long term follow up

Abstract Background PLATO study showed that Ticagrelor (Ti) significantly reduced the rate of death from vascular causes, myocardial infarction or stroke without a significant increase of major bleeding vs Clopidogrel (Cl). Previous studies demonstrated the stronger direct anti-platelet effect of Ti versus Cl. Few data exist about the indirect anti-platelet properties and pleiotropic effects, eventually involved in the positive effect of Ti on acute coronary syndrome (ACS) outcome. Aim As Ti has multiple pleiotropic effects, we sought to assess whether the different outcome of Ti versus Cl in NSTE-ACS patients could be explained, at least in part, by different modulation of circulating microRNA (miRNA). The primary endpoint was to characterize the effect of the two different P2Y12 inhibitors on miRNA expression. Secondary endpoint was to correlate miRNA profile to clinical outcome. Methods Thirty-one patients with a diagnosis of NSTE-ACS were enrolled in this study. Patients were randomized for Ti or Cl assumption before undergoing PCI. Clinical characteristics were homologues between Ti and Cl groups. Blood samples were drawn at different time point (T0, T1 and T2) to test miRNA modulation and stability (T0, at baseline; T1, three hours after drug administration; T2, twenty-four hours after coronarography). Plasma RNA was extracted and pooled for microarray PCR based panel of ninety miRNA analysis. MiRNA expression was normalized on the global mean of each patient. Levels of circulating miRNAs were compared using statistical tests, assuming significance at P<0,05. Results A panel of seven circulating miRNAs associated with atherosclerosis, thrombosis and inflammation were selected for validation (miR-652-3p; miR-26-5p; miR-25-3p; miR-let7c; miR-155-5p; miR-222-3p; miR-223-3p). Microarray analysis showed an opposite modulation of most miRNAs at T0, T1 and T2 in patients with Cl or Ti treatment. In particular, Cl group showed an upregulation of most miRNAs, while Ti administration caused their down-regulation. Of the seven miRNA selected for validation, miR-652-3p, expression at T1 showed a significantly modulation in patients in Cl treatment compared to Ti (T1 Cl 2,637±1,092, T1 Ti 0,660±0,171; p=0.03). MiRNA-652-3p has a validated pro-atherogenic role. On five-years follow, an higher rate (40%) of cardiovascular events (new ACS, recurrent ischemia and stent thrombosis) was reported in the Cl group compare to Ti. Indeed, no one death or bleeding occurred. Conclusion This data suggest that Ti has a protective role down-regulating pro-atherogenic and pro-thrombotic miRNAs (miR-652-3p, miR-let7c, miR-223-3p, miR-155-5p) and promoting the expression of anti-atherogenic miRNAs (miR-25-3p) when compared to Cl. This may contribute to explain the positive effect on clinical outcome of Ti. Although the small number of patients, this pilot study gives another evidence about the multiple positive pleiotropic effect of Ti. Figure 1. miRNA 652-3p expression Funding Acknowledgement Type of funding source: None

Serum Lipoprotein(a) levels on clinical outcomes after endovascular therapy

Abstract Background While lipoprotein (a) (Lp(a)) is an independent predictor of atherosclerotic diseases involving the coronary and cerebrovascular arteries, its prognostic value in patients with peripheral artery disease (PAD) remains still unclear. Objective The aim of study is to determine the role of Lp(a) levels after endovascular therapy (EVT). Methods This study was prospective observational study. From September 2016 to April 2019, 676 the patients (873 limbs) who underwent EVT for de-novo PAD were enrolled. We divided into Lp(a) levels ≥40 mg/dl (high Lp(a) group; n=129) and <40 mg/dl (low Lp(a) group; n=547). Outcome measures were major adverse cardiovascular events (MACE; all-cause death, myocardial infarction and stroke), and major adverse limb events (MALE; repeat revascularization for limb and major amputation) at 1 year. Major amputation defined as above forefoot amputation due to vascular cause. Results The mean follow-up period was 14.3±8.9 months. Serum Lp(a) levels before EVT were 27.2 (10.0–36.0 mg/dl). High Lp (a) group was significantly older, higher prevalence of history of stroke, chronic kidney disease, and multi-vessel lesions. Cumulative incidence of MACE at 1 year was not significantly between two groups (p=0.53, log-rank test), whereas cumulative incidence of MALE at 1 year was significantly higher in high Lp (a) group (p=0.04, log-rank test). However, after adjusting for prespecified risk factors, high Lp (a) group was not independent predictor in MALE at 1 year. Conclusion High Lp (a) might not be associated with cardiovascular events and limb prognosis after EVT for PAD in early phase. Funding Acknowledgement Type of funding source: None

Fenotyp akútneho hepatálneho zlyhania pri inaparentnom malobunkovom karcinóme pľúc

Acute liver failure is defined by the manifestation of liver failure from 7th to 21st day in a previously healthy liver. The most frequent causes are viral hepatitis B, A, E, drug or toxin-induced hepatotoxicity (Amanita phalloides), rarely Wilson’s disease, autoimmune hepatitis, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, or vascular causes (Budd-Chiari syndrome, hypoxic hepatitis). We present a 71-year- -old female patient with metabolic syndrome admitted to hospital with cholestasis, progression of weakness, abdominal pain, and breathlessness. Because of suspected pleuropneumonia, the treatment with ceftriaxone/metronidazole was initiated. Due to cholestasis progression and suspicion of drug-induced liver toxicity, the treatment was stopped on 5th day. Imaging methods (ultrasonography, CT, magnetic resonance imaging) found multiple small liver lesions, suspected metastatic involvement, which was not confirmed by positron emission tomography – computed tomography. Due to the rapid progression of the patient’s condition with the onset of icterus, ascites, encephalopathy, a liver bio­psy was not done. The patient died on the 17th day of hospitalization. The primary tumour was not detected during her life, and not by pathological section. The diffuse metastasis of small cell lung cancer (SCLC) in the liver was found by histological post mortem examination. The case report suggests high invasiveness of SCLC with a possibility of unusual manifestation in a form of acute hepatic failure.

Non Communicable Diseases: Challenge Ahead

Non-communicable diseases (NCDs) are of long duration and generally of slow progress. The four main groups of NCDs are Cardio-vascular diseases, Cancers, Chronic Respiratory diseases and Diabetes. The NCDs kill 38 million people worldwide annually (63% of global deaths). Almost three quarters of the NCD deaths (28 million) occur in the low and middle income countries. Sixteen million deaths due to NCDs are premature, occurring before the age of 70 years; and 82% of these premature deaths occur in the low and middle income countries. These four groups of diseases account for 82% of all NCD deaths: cardiovascular diseases 17.5 million, cancers 8.2 million, chronic respiratory diseases 4 million and diabetes 1.5 million. In India, 60% of all deaths are attributable to NCDs, making them the leading cause of death- ahead of injuries and communicable, maternal, prenatal, and nutritional conditions. The NCDs account for about 40% of all hospital stays and roughly 35% of all recorded outpatient visits in India. The globalization of unhealthy life styles, which are recognized as the modifiable risk factors, like tobacco use, physical inactivity, harmful use of alcohol and unhealthy diets are the key factors that increase the risk of dying from the NCDs. The unhealthy behaviours lead to four key metabolic/ physiological changes (called the intermediate risk factors of NCDs) i.e. raised blood pressure, overweight/ obesity, raised blood glucose and dyslipidaemia that increase the risk of NCDs. The underlying determinants of NCDs mainly exist in non-health sectors, such as agriculture, urban development, education and trade. In terms of attributable deaths, the leading metabolic risk factor globally is elevated blood pressure (to which 18% of global deaths are attributed), followed by overweight and obesity and raised blood glucose. Tobacco accounts for around 6 million deaths every year and is projected to increase to 8 million by 2030. About 3.2 million deaths annually can be attributed to insufficient physical activity. In 2010, 1.7 million annual deaths from cardio vascular causes have been attributed to excess salt intake. More than 3.3 million annual deaths are attributed to harmful drinking of alcohol.

S2726 No Biopsy Saves Life! Rare Incidence of Liver Transplantation for Unknown T-Cell Lymphoma-Induced Acute Liver Failure

INTRODUCTION: Acute liver failure (ALF) is a rare condition characterized by acute hepatic injury causing rapid onset of coagulopathy and encephalopathy. Without prompt treatment, ALF carries an exceptionally high morbidity and mortality, and prognosis is particularly poor when ALF is attributed to malignant infiltration. We present a case of ALF of initially unknown etiology that required expedited liver transplantation. The patient was subsequently diagnosed with hepatic T-cell lymphoma, which is a potentially transplant disqualifying condition. Post-transplant, the patient completed chemotherapy and made a full recovery. CASE DESCRIPTION/METHODS: A 21-year-old male soldier without prior medical history was evacuated from an overseas deployment for 2 weeks of headaches, fatigue, nausea, and vomiting. Scleral icterus had developed in conjunction with diminished hepatic synthetic function (INR 2.8 not responsive to Vitamin K), hyperbilirubinemia (total bilirubin 12.4 mg/dL), and elevated transaminase levels (ALT/AST 1000/705 U/L). Upon stateside evaluation, he developed asterixis and progressive encephalopathy. The history obtained from the patient was reliably negative for toxic ingestions or suspect environmental exposures. The workup for vascular causes, viral and autoimmune hepatitis, Wilson disease, hemochromatosis, and alpha-1-antitrypsin deficiency was negative. An empiric treatment with n-acetylcysteine was ineffective. Per the ALF Study Group estimation, the patient had a 9% 21-day transplant free survival, and was promptly transferred to a transplant center. A liver biopsy was deferred given coagulopathy and rapid decompensation that required vasopressors and intracranial pressure reduction as a bridge to transplant. His explant demonstrated T-cell rich lymphoma with no hyper-metabolic lesions on PET scan. The patient fully recovered from surgery, completed chemotherapy, and remains in clinical remission on his immunosuppressive regimen. DISCUSSION: Less than 40 cases of ALF from hepatic lymphoma have been reported in the literature, with a majority diagnosed post-mortem. Prognosis is generally poor, and rapid clinical deterioration prompts difficult and swift decisions often based on an incomplete data set. As described with this young patient with ALF of initially unknown etiology, proceeding with liver transplant was the only life-saving option. This case demonstrates that a consideration must be made to transplant potentially disqualifying conditions that have effective established therapies.Figure 1.: Diagnostic CD3 stain for T-cell rich lymphoma.Figure 2.: Diagnostic CD20 stain for T-cell rich lymphoma.

Upside-down kidney placement: An alternative in pediatric renal transplantation

Purpose“Upside-down” kidney placement has been reported as an acceptable alternative in cases of technical difficulty in kidney transplantation but there are few reports in the pediatric population.The aim of our study is to analyze whether the placement of the upside-down kidney could affect graft outcome or produce more complications. Materials and methodsA retrospective study was conducted of pediatric kidney transplants performed in our center between 2005 and 2017 with at least 6 months' follow-up.Epidemiological and anthropometric data, type of donor (deceased/living), graft position (normal/upside-down), reason for the upside-down placement, early, medium and long-term complications and renal function were analyzed and compared with patients transplanted in the same period with a normal graft placement. ResultsFrom 181 transplants, 167 grafts were placed in a normal position (mean age: 10 y and mean weight: 30 kg) and 14 were placed upside-down (10 y, 37 kg) mainly because of vessel shortness after laparoscopic nephrectomy. Male predominance was observed in both groups.57% of grafts from the control group and 64% of those from study group came from a living donor.Four vascular and two ureteral re-anastomoses were recorded in the control group and two vascular and one ureteral re-anastomosis in the study group (p > 0.05). In the latter group, no grafts have been lost due to vascular or urological causes and no patients have required dialysis. ConclusionsWhen necessary, an upside-down placement for the renal graft is a safe alternative in the pediatric population. Level of evidenceLevel III.

Retinal and Optic Nerve Deformations Due to Orbital Versus Intracranial Venous Hypertension.

Abnormal forces around the optic nerve head (ONH) due to orbital diseases, intracranial hypertension (IH), glaucoma, and space travel, are associated with alterations of the ONH shape. Elevated cerebral and ophthalmic venous pressure can contribute to stress and strain on the ONH and peripapillary retina. We hypothesize that IH and elevated ophthalmic venous pressure without IH cause different ONH and retinal changes. We compared MRI and spectral domain optical coherence tomography (SDOCT) findings in patients with cavernous sinus arteriovenous shunts (CSAVSs), where orbital venous pressure is known to be elevated, with patients with intracranial dural venous sinus thrombosis and secondary IH. We also compared the results to those obtained in the Idiopathic IH (IIH) Treatment Trial. Among 18 patients with dural venous sinus thrombosis, the MRI/magnetic resonance venography displayed partial empty sella (61%) and optic nerve sheath distension (67%). None exhibited ophthalmic vein dilation or signs of orbital congestion. SDOCT of these eyes and IIH eyes showed a similar frequency of abnormal thickening of the mean retinal nerve fiber layer, anterior displacement of the basement membrane opening, peripapillary wrinkles, retinal folds (RF), and choroidal folds (CF). Among 21 patients with CSAVSs, MRI showed ipsilateral dilated superior ophthalmic vein (76%) and orbital congestion (52%) without distension of the optic nerve sheath or globe distortion. SDOCT showed CF (19%), one with overlying RF, and no ONH deformations. SDOCT findings for dural venous sinus thrombosis are similar to those seen with IIH but distinct from changes due to local ophthalmic venous hypertension. These data support the concept that IH even if due to a vascular cause and local orbital venous hypertension cause different stresses and strains on the ONH.

Timing of Oral P2Y12 Inhibitor Administration in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

BackgroundAlthough oral P2Y12 inhibitors are key in the management of patients with non–ST-segment elevation acute coronary syndrome, the optimal timing of their administration is not well defined. ObjectivesThe purpose of this study was to compare downstream and upstream oral P2Y12 inhibitors administration strategies in patients with non–ST-segment elevation acute coronary syndrome undergoing invasive treatment. MethodsWe performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit). ResultsWe randomized 1,449 patients to downstream or upstream oral P2Y12 inhibitor administration. A pre-specified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes; nonfatal myocardial infarction or nonfatal stroke; and Bleeding Academic Research Consortium type 3, 4, and 5 bleeding through day 30, did not differ significantly between the downstream and upstream groups (percent absolute risk reduction: –0.46; 95% repeated confidence interval: –2.90 to 1.90). These results were confirmed among patients undergoing percutaneous coronary intervention (72% of population) and regardless of the timing of coronary angiography (within or after 24 h from enrollment). ConclusionsDownstream and upstream oral P2Y12 inhibitor administration strategies were associated with low incidence of ischemic and bleeding events and minimal numeric difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of 1 strategy over the other. (Downstream Versus Upstream Strategy for the Administration of P2Y12 Receptor Blockers In Non-ST Elevated Acute Coronary Syndromes With Initial Invasive Indication [DUBIUS]; NCT02618837)

Etiology of testicular pain 2019: Classification into ten logical subgroups

Background: Testicular pain encompasses a vast medical diagnostic field, with numerous organ and system convergence. Acute testicular pain is a medical emergency that requires accurate evaluation and immediate resolution, whereas chronic testicular pain is enigmatic and requires sound knowledge of the mechanisms of testicular pain and the differential diagnosis.
 Objective: To review the causes of testicular pain and propose a new etiologic classification consisting of 10 subgroups. 
 Methods: A bibliographic search was carried out utilizing Google and the National Library of Medicine’s PubMed databases to identify original articles and review articles (hard copy or electronic) published on testicular pain, up to March 2020. The search included: MeSH terms: testicular disease (classification, complications, etiology, trauma, microbiology, pathology, pathophysiology, secondary, surgery, treatment) and vasectomy; Non-MeSH terms: acute and chronic orchialgia, scrotalgia, orchidynia, groin pain, epididymalgia, testalgia, chronic testicular pain, chronic scrotal pain syndrome, testicular pain syndrome, epididymal pain syndrome, and post-vasectomy pain syndrome. The initial search produced 625 articles, of which 143 were included in the present review.
 Results: To better understand testicular pain etiology, 100 possible diagnoses were divided into ten subgroups: infectious, neoplastic, traumatic, torsional, vascular, immunologic, neurologic, pharmacologic, obstructive, and miscellaneous causes. Likewise, treatment can be divided into two main groups, according to therapeutic options: pharmacologic and non-pharmacologic, with the latter subdivided into: noninvasive and the increasingly performed invasive (surgical) alternatives.
 Conclusions: Testicular pain should be understood as a complex pain syndrome of enigmatic origin. Treatment success depends on the correct identification, from hundreds of possibilities, of the cause of pain. Logical grouping of those possibilities could aid in making the accurate etiologic identification.

Etiology of testicular pain 2019: Classification into ten logical subgroups

Background: Testicular pain encompasses a vast medical diagnostic field, with numerous organ and system convergence. Acute testicular pain is a medical emergency that requires accurate evaluation and immediate resolution, whereas chronic testicular pain is enigmatic and requires sound knowledge of the mechanisms of testicular pain and the differential diagnosis.
 Objective: To review the causes of testicular pain and propose a new etiologic classification consisting of 10 subgroups. 
 Methods: A bibliographic search was carried out utilizing Google and the National Library of Medicine’s PubMed databases to identify original articles and review articles (hard copy or electronic) published on testicular pain, up to March 2020. The search included: MeSH terms: testicular disease (classification, complications, etiology, trauma, microbiology, pathology, pathophysiology, secondary, surgery, treatment) and vasectomy; Non-MeSH terms: acute and chronic orchialgia, scrotalgia, orchidynia, groin pain, epididymalgia, testalgia, chronic testicular pain, chronic scrotal pain syndrome, testicular pain syndrome, epididymal pain syndrome, and post-vasectomy pain syndrome. The initial search produced 625 articles, of which 143 were included in the present review.
 Results: To better understand testicular pain etiology, 100 possible diagnoses were divided into ten subgroups: infectious, neoplastic, traumatic, torsional, vascular, immunologic, neurologic, pharmacologic, obstructive, and miscellaneous causes. Likewise, treatment can be divided into two main groups, according to therapeutic options: pharmacologic and non-pharmacologic, with the latter subdivided into: noninvasive and the increasingly performed invasive (surgical) alternatives.
 Conclusions: Testicular pain should be understood as a complex pain syndrome of enigmatic origin. Treatment success depends on the correct identification, from hundreds of possibilities, of the cause of pain. Logical grouping of those possibilities could aid in making the accurate etiologic identification.

Tentorial Dural Arteriovenous Fistulas as a Cause of Thalamic Edema: 2 Cases of an Important Differential Diagnosis to Consider.

The differential diagnosis for bilateral thalamic edema is extensive and includes vascular, neoplastic, metabolic, and infectious causes. Of the vascular causes of thalamic edema, arterial and venous infarctions are well-documented, but dural arteriovenous fistulas (dAVFs) are a relatively uncommon and widely underrecognized cause of thalamic edema. Dural AVFs are notoriously difficult to diagnose clinically, especially in the absence of hemorrhage, and cross-sectional imaging findings can be subtle. This can result in a delayed diagnosis, and occasionally, an invasive biopsy for further clarification of a purely vascular disease. In this review, we detail our experience with the imaging diagnosis of dAVF as a cause of thalamic edema and present a short differential of other vascular causes.