Long-Term Outcome in Patients With Spinal Cord Stimulation for Failed Back Surgery Syndrome: A 20-Year Audit of a Single Center.

STUDY DESIGN: This is a retrospective, observational study. INTRODUCTION: Spinal cord stimulation (SCS) has found its application in chronic pain treatment, with failed back surgery syndrome (FBSS) as one of the most important indications. However, to date, little is known about the long-term effectiveness of the treatment. The aim of this study is to analyze retrospectively the long-term outcomes of SCS treatment in a single multidisciplinary pain center on predominant radicular pain, using devices of a single manufacturer. MATERIALS AND METHODS: Patient data on overall patient satisfaction, pain intensity, and adverse events were retrospectively collected in our clinical practice between January 1998 and January 2018, for 191 patients who received a permanent SCS implant. Secondary health measures included the influence of opioid and nicotine use on pain reduction after therapy. RESULTS: The trial-to-implant ratio was 93.6%. At a mean follow-up of 10.6 years, 78.5% of the patients were satisfied with the treatment outcome, with a significant pain reduction of an average three points on a Numeric Rating Scale. Opioid and nicotine usage did not have a significant link with the pain reduction one year after the treatment. Furthermore, devices had an average battery lifespan of 8.4 years. A total of 248 revisions were recorded. A total of 24 patients (11.7%) acquired an infection; 7 of 204 patients had an infection during the trial period, 2 of 191 patients had an infection in the first postoperative year, and 15 of 191 patients had an infection after the first year. The average time to infection, if not in the first year, was 10.1 years. CONCLUSIONS: A successful long-term outcome regarding pain relief in patients with predominant radicular pain due to FBSS is established with SCS therapy.

Association between postoperative delirium and postoperative cerebral oxygen desaturation in older patients after cardiac surgery.

BACKGROUND: Near-infrared spectroscopy non-invasively measures regional cerebral oxygen saturation. Intraoperative cerebral desaturations have been associated with worse neurological outcomes. We investigated whether perioperative cerebral desaturations are associated with postoperative delirium in older patients after cardiac surgery. METHODS: Patients aged 70 yr and older scheduled for on-pump cardiac surgery were included between 2015 and 2017 in a single-centre, prospective, observational study. Baseline cerebral oxygen saturation was measured 1 day before surgery. Throughout surgery and after ICU admission, cerebral oxygen saturation was monitored continuously up to 72 h after operation. The presence of delirium was assessed using the confusion assessment method for the ICU. Association with delirium was evaluated with unadjusted analyses and multivariable logistic regression. RESULTS: Ninety-six of 103 patients were included, and 29 (30%) became delirious. Intraoperative cerebral oxygen saturation was not significantly associated with postoperative delirium. The lowest postoperative cerebral oxygen saturation was lower in patients who became delirious (P=0.001). The absolute and relative postoperative cerebral oxygen saturation decreases were more marked in patients with delirium (13 [6]% and 19 [9]%, respectively) compared with patients without delirium (9 [4]% and 14 [5]%; P=0.002 and P=0.001, respectively). These differences in cerebral oxygen saturation were no longer present after excluding cerebral oxygen saturation values after patients became delirious. Older age, previous stroke, higher EuroSCORE II, lower preoperative Mini-Mental Status Examination, and more substantial absolute postoperative cerebral oxygen saturation decreases were independently associated with postoperative delirium incidence. CONCLUSIONS: Postoperative delirium in older patients undergoing cardiac surgery is associated with absolute decreases in postoperative cerebral oxygen saturation. These differences appear most detectable after the onset of delirium. CLINICAL TRIAL REGISTRATION: NCT02532530.

Screening for hepatitis C at the emergency department: Should babyboomers also be screened in Belgium?

BACKGROUND & AIMS: Patients are not screened adequately for hepatitis C virus infection in Belgium. In the USA, the Center for Disease Control recommends screening for patients born in the babyboom period (1945-1965). In Europe, the babyboom cohort was born between 1955 and 1974, but no screening policy has been targeted to this group. We aimed to study the prevalence of hepatitis C virus in an emergency department population in Belgium and the risk factors associated with hepatitis C virus infection. METHOD: We performed a monocentric, cross-sectional seroprevalence study between January and November 2017 in a large Belgian non-university hospital. Patients aged 18-70 years presenting at the emergency department were eligible. Patients completed a risk assessment questionnaire and were screened for hepatitis C virus antibodies (Ab) with reflex hepatitis C virus ribonucleic acid testing. RESULTS: Of 2970 patients, 2366 (79.7%) agreed to participate. hepatitis C virus Ab prevalence was 1.31%. Twenty-one (67.7%) hepatitis C virus Ab-positive patients were born between 1955 and 1974. With a previous treatment uptake of 54.5%, the prevalence of viremia was 0.9% in retrospect; 0.2% were newly diagnosed. The weighted multiple logistic regression model identified males born in the 1955-1974 cohort, intravenous drug use and high endemic birth country as significant risk factors for hepatitis C virus infection (P < 0.05). CONCLUSION: Although the prevalence of hepatitis C virus Ab at the emergency department was higher than previously estimated for the general population in Belgium, the number of newly diagnosed patients with viremia was low. To optimize screening strategies, screening should be offered to males born in the 1955-1974 cohort, but especially in drug users, the prison population and immigrants from high endemic countries.

Does the Use of Epiduroscopic Lysis of Adhesions Reduce the Need for Spinal Cord Stimulation in Failed Back Surgery Syndrome? A Short-Term Pilot Study.

BACKGROUND AND AIMS: Persistent low back pain after initially successful surgery that is not attributed to structural deficits is called failed back surgery syndrome (FBSS). When conservative and minimal invasive therapy fail, the recommended treatment is spinal cord stimulation (SCS). Because epidural fibrosis can be a contributing factor in the majority of FBSS patients, lumbosacral epiduroscopic lysis of adhesions may be considered as a less invasive alternative treatment option. We hypothesized that the use of epiduroscopic lysis of adhesions could reduce the need for SCS. METHODS: A pilot study was performed in 35 consecutive patients with FBSS who underwent epiduroscopic lysis of adhesions. SCS was considered if epiduroscopic lysis of adhesions gave less than 50% global perceived effect (GPE) improvement after 15 months of follow-up. The GPE was measured 1 week and 6 months after the procedure. RESULTS: Over a period of 69 months, 35 patients were included. After 15 months of follow-up, 43% of patients required SCS. Eight of the 15 patients who reported no short-term improvement needed SCS; those patients had severe epidural fibrosis. One week after epiduroscopic lysis of adhesions, 34%, 23%, and 43% of patients reported GPE improvement of > 50%, 20% to 50%, and < 20%, respectively. After 6 months, 5 patients were lost to follow-up, and 30%, 17%, and 16% of patients reported improvement of > 50%, 20% to 50%, and < 20%, respectively. CONCLUSIONS: In this pilot study we observed a reduced need for SCS when lumbosacral epiduroscopic lysis of adhesions was used for patients with FBSS and magnetic resonance imaging-proven adhesions. These observations justify the evaluation of both treatment options in a prospective observational trial.

The Effect of Deep Versus Moderate Neuromuscular Block on Surgical Conditions and Postoperative Respiratory Function in Bariatric Laparoscopic Surgery: A Randomized, Double Blind Clinical Trial.

BACKGROUND: In recent literature, it has been suggested that deep neuromuscular block (NMB) improves surgical conditions during laparoscopy; however, the evidence supporting this statement is limited, and this was not investigated in laparoscopic bariatric surgery. Moreover, residual NMB could impair postoperative respiratory function. We tested the hypotheses that deep NMB could improve the quality of surgical conditions for laparoscopic bariatric surgery compared with moderate NMB and investigated whether deep NMB puts patients at risk for postoperative respiratory impairment compared with moderate NMB. METHODS: Sixty patients were evenly randomized over a deep NMB group (rocuronium bolus and infusion maintaining a posttetanic count of 1-2) and a moderate NMB group (rocuronium bolus and top-ups maintaining a train-of-four count of 1-2). Anesthesia was induced and maintained with propofol and remifentanil. The primary outcome measures were the quality of surgical conditions assessed by a single surgeon using a 5-point rating scale (1 = extremely poor, 5 = optimal), the number of intra-abdominal pressure increases >18 cmH2O and the duration of surgery. Secondary outcome measure was the postoperative pulmonary function assessed by peak expiratory flow, forced expiratory volume in 1 second, and forced vital capacity, and by the need for postoperative respiratory support. Data are presented as mean ± standard deviation with estimated treatment effect (ETE: mean difference [95% confidence interval]) for group comparisons. RESULTS: There was no statistically significant difference in the surgeon's rating regarding the quality of the surgical field between the deep and moderate NMB group (4.2 ± 1.0 vs 3.9 ± 1.1; P = .16, respectively; ETE: 0.4 [-0.1, 0.9]). There was no difference in the proportional rating of surgical conditions over the 5-point rating scale between both groups (P = .91). The number of intra-abdominal pressure increases >18 cmH2O and the duration of surgery were not statistically different between the deep and moderate NMB group (0.2 ± 0.9 vs 0.3 ± 1.0; P = .69; ETE: -0.1 [-0.5, 0.4] and 61.3 ± 15.1 minutes vs 70.6 ± 20.8 minutes; P = .07, ETE: -9.3 [-18.8, 0.1], respectively). All the pulmonary function tests were considerably impaired in both groups when compared with baseline (P < .001). There was no statistically significant difference in the decrease in peak expiratory flow, forced expiratory volume in 1 second, and forced vital capacity (expressed as % change from baseline) between the deep and the moderate NMB group. CONCLUSIONS: Compared with a moderate NMB, there was insufficient evidence to conclude that deep NMB improves surgical conditions during laparoscopic bariatric surgery. Postoperative pulmonary function was substantially decreased after laparoscopic bariatric surgery independently of the NMB regime that was used. The study is limited by a small sample size.

Effect of minocycline on lumbar radicular neuropathic pain: a randomized, placebo-controlled, double-blind clinical trial with amitriptyline as a comparator.

BACKGROUND: Less than 50% of patients experience sufficient pain relief with current drug therapy for neuropathic pain. Minocycline shows promising results in rodent models of neuropathic pain but was not studied in humans with regard to the treatment of neuropathic pain. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, patients with subacute lumbar radicular pain received placebo, amitriptyline 25 mg, or minocycline 100 mg once a day (n = 20 per group) for 14 days. Primary outcome measure was the pain intensity in the leg as measured by a numeric rating scale ranging from 0 to 10 on days 7 and 14. Secondary outcome measures were the reduction of neuropathic pain symptoms in the leg as determined with a neuropathic pain questionnaire, consumption of rescue medication, and adverse events on days 7 and 14. RESULTS: Sixty patients were randomized and included in an intention-to-treat analysis. After 14 days, patients in the minocycline and amitriptyline groups reported a reduction of 1.47 (95% confidence interval, 0.16-2.83; P = 0.035) and 1.41 (95% confidence interval, 0.05-2.78; P = 0.043), respectively, in the numeric rating scale compared to the placebo group. No differences were seen in the neuropathic pain questionnaire values at any time point during treatment between the three groups. The rate of adverse events in the amitriptyline group was 10% versus none in the minocycline and placebo groups. No differences were noted in the consumption of rescue medication. CONCLUSIONS: Although both groups differed from placebo, their effect size was small and therefore not likely to be clinically meaningful.

Unintentional cervical dural tap treated with lumbar blood patch.

Cervical radicular pain presents itself as pain radiating from the neck to the arm. If conservative treatment fails, a cervical epidural steroid injection can be considered. A rare but possible complication resulting from the interlaminar approach is unintentional cervical dural puncture that may result in post-dural puncture headache (PDPH). Dural puncture from an interlaminar cervical epidural injection reportedly range from 0.25% to 2.65%. An epidural blood patch is a possible treatment option when conservative treatment fails. Relief could be secondary to 'sealing' of the dural tear from the clotted blood and reestablishment of physiological intracranial pressure. Another theory is an increase in the subarachnoid pressure from the injected blood. The increased pressure may restore normal intracranial pressure. We describe 2 cases of cervical PDPH treated with lumbar epidural blood patch. In 1 case, there was complete resolution of the symptoms and in the other case, there was great improvement of symptoms and a high thoracic blood patch was performed to resolve the remaining headache.

Epiduroscopy for patients with lumbosacral radicular pain.

Lumbosacral radicular pain is a pain in the distribution area of one of the nerves of the lumbosacral plexus, with or without sensory and/or motor impairment. A major source of lumbosacral radicular pain is failed back surgery, which is defined as persistent or recurrent pain, mainly in the region of the lower back and legs even after technically, anatomically successful spine surgeries. If lumbosacral radicular neuropathic pain fails to respond to conservative or interventional treatments, epiduroscopy can be performed as part of a multidisciplinary approach. Epiduroscopy aids in identifying painful structures in the epidural space, establishing a diagnosis and administering therapy. The novelty consists in the use of an epiduroscope to deliver therapies such as adhesiolysis and targeted administration of epidural medications. Clinical trials report favorable treatment outcomes in 30% to 50% of patients. Complications are rare and related to the rate or volume of epidural fluid infusion or inadvertent dural puncture. In patients with lumbosacral radicular pain, especially after back surgery, epiduroscopy with adhesiolysis may be considered (evidence rating 2 B+).

Radiofrequency treatment of facet-related pain: evidence and controversies.

Pain originating from the lumbar facet joints is estimated to represent about 15% of all low back pain complaints. The diagnostic block is considered to be a valuable tool for confirming facetogenic pain. It was demonstrated that a block of the ramus medialis of the ramus dorsalis is preferred over an intra-articular injection. The outcome of the consequent radiofrequency treatment is not different in patients reporting over 80% pain relief after the diagnostic block than in those who have between 50% and 79% pain relief. There is one well-conducted comparative trial assessing the value of one or two controlled diagnostic blocks to none. The results of the seven randomized trials on the use of radiofrequency treatment of facet joint pain demonstrate that good patient selection is imperative for good clinical outcome. Therefore, we suggest one block of the ramus medialis of the ramus dorsalis before radiofrequency treatment.

Population-wide persistent hemostatic changes after vaccination with ChAdOx1-S.

Various vaccines were developed to reduce the spread of the Severe Acute Respiratory Syndrome Cov-2 (SARS-CoV-2) virus. Quickly after the start of vaccination, reports emerged that anti-SARS-CoV-2 vaccines, including ChAdOx1-S, could be associated with an increased risk of thrombosis. We investigated the hemostatic changes after ChAdOx1-S vaccination in 631 health care workers. Blood samples were collected 32 days on average after the second ChAdOx1-S vaccination, to evaluate hemostatic markers such as D-dimer, fibrinogen, α2-macroglobulin, FVIII and thrombin generation. Endothelial function was assessed by measuring Von Willebrand Factor (VWF) and active VWF. IL-6 and IL-10 were measured to study the activation of the immune system. Additionally, SARS-CoV-2 anti-nucleoside and anti-spike protein antibody titers were determined. Prothrombin and fibrinogen levels were significantly reduced after vaccination (-7.5% and -16.9%, p < 0.0001). Significantly more vaccinated subjects were outside the normal range compared to controls for prothrombin (42.1% vs. 26.4%, p = 0.026) and antithrombin (23.9% vs. 3.6%, p = 0.0010). Thrombin generation indicated a more procoagulant profile, characterized by a significantly shortened lag time (-11.3%, p < 0.0001) and time-to-peak (-13.0% and p < 0.0001) and an increased peak height (32.6%, p = 0.0015) in vaccinated subjects compared to unvaccinated controls. Increased VWF (+39.5%, p < 0.0001) and active VWF levels (+24.1 %, p < 0.0001) pointed toward endothelial activation, and IL-10 levels were significantly increased (9.29 pg/mL vs. 2.43 pg/mL, p = 0.032). The persistent increase of IL-10 indicates that the immune system remains active after ChAdOx1-S vaccination. This could trigger a pathophysiological mechanism causing an increased thrombin generation profile and vascular endothelial activation, which could subsequently result in and increased risk of thrombotic events.

8. Occipital neuralgia.

Occipital neuralgia is defined as a paroxysmal shooting or stabbing pain in the dermatomes of the nervus occipitalis major and/or nervus occipitalis minor. The pain originates in the suboccipital region and radiates over the vertex. A suggestive history and clinical examination with short-term pain relief after infiltration with local anesthetic confirm the diagnosis. No data are available about the prevalence or incidence of this condition. Most often, trauma or irritation of the nervi occipitales causes the neuralgia. Imaging studies are necessary to exclude underlying pathological conditions. Initial therapy consists of a single infiltration of the culprit nervi occipitales with local anesthetic and corticosteroids (2 C+). The reported effects of botulinum toxin A injections are contradictory (2 C+/-). Should injection of local anesthetic and corticosteroids fail to provide lasting relief, pulsed radio-frequency treatment of the nervi occipitales can be considered (2 C+). There is no evidence to support pulsed radio-frequency treatment of the ganglion spinale C2 (dorsal root ganglion). As such, this should only be done in a clinical trial setting. Subcutaneous occipital nerve stimulation can be considered if prior therapy with corticosteroid infiltration or pulsed radio-frequency treatment failed or provided only short-term relief (2 C+).

12. Pain originating from the lumbar facet joints.

Although the existence of a "facet syndrome" had long been questioned, it is now generally accepted as a clinical entity. Depending on the diagnostic criteria, the zygapophysial joints account for between 5% and 15% of cases of chronic, axial low back pain. Most commonly, facetogenic pain is the result of repetitive stress and/or cumulative low-level trauma, leading to inflammation and stretching of the joint capsule. The most frequent complaint is axial low back pain with referred pain perceived in the flank, hip, and thigh. No physical examination findings are pathognomonic for diagnosis. The strongest indicator for lumbar facet pain is pain reduction after anesthetic blocks of the rami mediales (medial branches) of the rami dorsales that innervate the facet joints. Because false-positive and, possibly, false-negative results may occur, results must be interpreted carefully. In patients with injection-confirmed zygapophysial joint pain, procedural interventions can be undertaken in the context of a multidisciplinary, multimodal treatment regimen that includes pharmacotherapy, physical therapy and regular exercise, and, if indicated, psychotherapy. Currently, the "gold standard" for treating facetogenic pain is radiofrequency treatment (1 B+). The evidence supporting intra-articular corticosteroids is limited; hence, this should be reserved for those individuals who do not respond to radiofrequency treatment (2 B±).

13. Sacroiliac joint pain.

The sacroiliac joint accounts for approximately 16% to 30% of cases of chronic mechanical low back pain. Pain originating in the sacroiliac joint is predominantly perceived in the gluteal region, although pain is often referred into the lower and upper lumbar region, groin, abdomen, and/ or lower limb(s). Because sacroiliac joint pain is difficult to distinguish from other forms of low back pain based on history, different provocative maneuvers have been advocated. Individually, they have weak predictive value, but combined batteries of tests can help ascertain a diagnosis. Radiological imaging is important to exclude "red flags" but contributes little in the diagnosis. Diagnostic blocks are the diagnostic gold standard but must be interpreted with caution, because false-positive as well as false-negative results occur frequently. Treatment of sacroiliac joint pain is best performed in the context of a multidisciplinary approach. Conservative treatments address the underlying causes (posture and gait disturbances) and consist of exercise therapy and manipulation. Intra-articular sacroiliac joint infiltrations with local anesthetic and corticosteroids hold the highest evidence rating (1 B+). If the latter fail or produce only short-term effects, cooled radiofrequency treatment of the lateral branches of S1 to S3 (S4) is recommended (2 B+) if available. When this procedure cannot be used, (pulsed) radiofrequency procedures targeted at L5 dorsal ramus and lateral branches of S1 to S3 may be considered (2 C+).

Prediction of Functional Outcome After Acute Ischemic Stroke: Comparison of the CT-DRAGON Score and a Reduced Features Set.

Background and Purpose: The CT-DRAGON score was developed to predict long-term functional outcome after acute stroke in the anterior circulation treated by thrombolysis. Its implementation in clinical practice may be hampered by its plethora of variables. The current study was designed to develop and evaluate an alternative score, as a reduced set of features, derived from the original CT-DRAGON score. Methods: This single-center retrospective study included 564 patients treated for stroke, in the anterior and the posterior circulation. At 90 days, favorable [modified Rankin Scale score (mRS) of 0-2] and miserable outcome (mRS of 5-6) were predicted by the CT-DRAGON in 427 patients. Bootstrap forests selected the most relevant parameters of the CT-DRAGON, in order to develop a reduced set of features. Discrimination, calibration and misclassification of both models were tested. Results: The area under the receiver operating characteristic curve (AUROC) for the CT-DRAGON was 0.78 (95% CI 0.74-0.81) for favorable and 0.78 (95% CI 0.72-0.83) for miserable outcome. Misclassification was 29% for favorable and 13.5% for miserable outcome, with a 100% specificity for the latter. National Institutes of Health Stroke Scale (NIHSS), pre-stroke mRS and age were identified as the strongest contributors to favorable and miserable outcome and named the reduced features set. While CT-DRAGON was only available in 323 patients (57%), the reduced features set could be calculated in 515 patients (91%) (p < 0.001). Misclassification was 25.8% for favorable and 14.4% for miserable outcome, with a 97% specificity for miserable outcome. The reduced features set had better discriminative power than CT-DRAGON for both outcomes (both p < 0.005), with an AUROC of 0.82 (95% CI 0.79-0.86) and 0.83 (95% CI 0.77-0.87) for favorable and miserable outcome, respectively. Conclusions: The CT-DRAGON score revealed acceptable discrimination in our cohort of both anterior and posterior circulation strokes, receiving all treatment modalities. The reduced features set could be measured in a larger cohort and with better discrimination. However, the reduced features set needs further validation in a prospective, multicentre study. Clinical Trial Registration: http://www.clinicaltrials.gov. Identifiers: NCT03355690, NCT04092543.

Hypoglycemia caused by siphoning of an insulin infusion.

STUDY OBJECTIVE: To determine--through reconstruction of a clinical situation in which a syringe filled with insulin was removed from the syringe pump, placed above the patient, then emptied into the patient--the different physical forces at work, and to examine the height of the syringe (and thus the hydrostatic force) necessary to move the plunger. DESIGN: Prospective study. SETTING: Research laboratory of a university. MEASUREMENTS: The clinical situation was simulated using eight 50-mL and eight 20-mL syringes. A pressure transducer, placed between the syringe and the extension tubing, measured the pressure difference over the extension tubing. The Poiseuille equation of the viscous resistance was used to calculate flow. MAIN RESULTS: The mean height needed for initiation of flow in the 50-mL syringes was 76 cm (range, 60-90 cm). In the 20-mL syringes, no flow could be generated up to heights of 200 cm. There was a large variability in the height and time required to generate flow in apparently identical syringes, probably due to differences in the static sticking of the plunger to the barrel. CONCLUSIONS: Studies testing the effect of siphoning using one syringe cannot be interpreted reliably. Smaller syringes are safer to avoid siphoning.

Addition of Liposome Bupivacaine to Bupivacaine HCl Versus Bupivacaine HCl Alone for Interscalene Brachial Plexus Block in Patients Having Major Shoulder Surgery.

BACKGROUND AND OBJECTIVES: We examined whether liposome bupivacaine (Exparel) given in the interscalene brachial plexus block lowers pain in the setting of multimodal postoperative pain management for major shoulder surgery. METHODS: Fifty-two adult patients were randomized to receive either 5 mL of 0.25% bupivacaine HCl immediately followed by 10 mL of liposome bupivacaine 133 mg (n = 26) or 15 mL of 0.25% standard bupivacaine alone (n = 26) in interscalene brachial plexus block. The primary outcome (worst pain in the first postoperative week) was assessed by the Modified Brief Pain Inventory short form. Secondary outcomes were overall satisfaction with analgesia (OBAS), functionality of the surgical arm, sleep duration, time to first opioid (tramadol) request and opioid consumption (mEq), sensory-motor block characteristics, and the occurrence of adverse effects. RESULTS: Worst pain was lower in patients given liposome bupivacaine added to standard bupivacaine than in patients given standard bupivacaine alone (generalized estimating equation [GEE] estimated marginal mean values, 3.6 ± 0.3 vs 5.3 ± 0.4 points on the Numeric Rating Scale, respectively, although the effect was modest, 1.6 ± 0.5; 95% confidence interval, 0.8-2.5). Total OBAS scores indicated greater satisfaction (GEE estimated marginal mean values, 1.8 ± 0.3 vs 3.3 ± 0.4 on total OBAS, respectively, with modest effect, difference, 1.4 ± 0.5; 95% confidence interval, 0.5-2.4). There were no differences in any of the other secondary outcomes. CONCLUSIONS: Liposome bupivacaine added to standard bupivacaine may lower pain and enhance patient's satisfaction in the first postoperative week even in the setting of multimodal analgesia for major shoulder surgery.This study was registered with clinicaltrials.gov (NCT02554357) on July 11, 2015, by Principal Investigator Catherine Vandepitte, MD.