Drainage Of Chronic Subdural Hematoma Research Articles

Analysis of risk factors for prolong hospitalization in chronic subdural hematoma undergoing single burr hole and drainage

Introduction
 Single burr hole surgery for Chronic subdural hematoma (CSDH) is commonly performed neurosurgical procedure with >90% favorable outcome and less hospital stay. However, sometimes hospital stay may be prolonged due to associated prognostic factors, even in patients with favorable outcome. This study aims to analyze the early outcome of single burr hole and drainage surgery and factors that may be associated with prolong hospitalization.
 Materials and method
 A retrospective analysis of the patients who underwent single burr hole and drainage for CSDH from sept 2017 to may 2020 in Nepal Mediciti hospital. The patients with B/L CSDH, who underwent double burr hole and drainage or craniotomy evacuation or conservatively managed patients were excluded from the study. Early outcome was assessed using Glasgow outcome score at 7 days. Effect of use of antiplatelet/ anticoagulant drugs, age, comorbidity, preoperative Glasgow coma score on number of hospital stay was analyzed. Chi-square test was used for statistical analysis in SPSS version 25.
 Results
 Out of 85 patients, 73 were male. Mean age was 63.8 years. Early outcome in 7 days was favorable with GOS (4-5) in 90.6%. The use of antiplatelet or anticoagulant drugs was more common amongst patients with age > 70 years (p=0.01). The number of hospital stay was associated with age (p=0.00), antiplatelet or anticoagulant drugs (p=0.00), comorbidities (p=0.001), preoperative GCS(P=0.001) and GOS at 7 days (p=0.001).
 Conclusion
 Single burr hole and drainage surgery for CSDH mostly produce favorable outcome. The use of antiplatelet or anticoagulant drugs is more common in patients above 70 years. Age, antiplatelet or anticoagulant drugs, comorbidities, preoperative GCS, GOS at 7 days are related with longer hospital stay.

A Rare Complication of Burr Hole Drainage of Chronic Subdural Hematoma

Chronic subdural hematoma is a common neurosurgical problem, especially in the elderly, which is frequently treated by burr hole drainage. Recurrence is the most frequent complication of chronic subdural hematoma surgery reported in literature. However, cerebrospinal fluid leak resulting subgaleal pseudomeningooele has been reported. We report a 67-year-old man who had burr hole drainage of chronic subdural hematoma and subsequently developed cerebrospinal fluid fistula which was drained by subdural drain inserted intraoperatively. A 67-year-old right-handed man who presented with nine days' history of progressive pan-cranial persistent headache following a fall from the bathroom associated with irrational behavior and weakness of the left side of the body. His Glasgow Coma Score (GCS) was 12/15, with generalized hypertonia, left-sided hemiparesis, and left-sided grade + 3 deep tendon reflexes. Brain computed tomography scan [Figure 1] showed right-sided fronto-temporoparietal chronic subdural hematoma with midline shift and effacement of the ipsilateral lateral ventricle. He had right frontal and right parietal burr holes, such as subdural hematoma and insertion of nonnegative subdural drain through the parietal burr hole. He developed cerebrospinal fluid leak, which drained into the drainage bag and subsequently managed conservatively. Cerebrospinal fluid leaks can occur following burr hole drainage of chronic subdural hematoma. Subdural drain inserted intraoperatively is helpful in preventing the sequelae of cerebrospinal fluid accumulation in the subdural and subgaleal spaces.

Single versus Double Burr Hole for Drainage of Chronic Subdural Hematoma: Randomized Controlled Study

Chronic subdural hematoma (CSDH) is one of the most common neurosurgical emergencies. Most neurosurgeons currently drained CSDH through single or double burr holes; however, few studies have compared the 2 approaches to drainage. The aim of this study is to compare the recurrent rate following double and single burr hole for CSDH in our practice. This is a randomized controlled study from January 2015 to December 2019 in a neurosurgical unit in Kaduna, Nigeria. All patients with imaging diagnosis of subacute or chronic subdural hematoma who enrolled in the study had either a single or double burr hole. Patients were followed up for 6 months after surgery to assess for recurrence. Data were analyzed using SPSS version 25 for Windows. The Fisher exact test was performed to compare the 2 treatment groups. A 2-sided P value < 0.05 was considered statistically significant. A total of 192 patients were enrolled in the study with 99 in the single-burr hole group and 93 in the double burr-hole group. The overall recurrence rate in this study was 2.6%. The recurrence rate in the single arm was 3%, and in the double arm it was 2.2%. There was no statistically significant difference in recurrence between the 2 groups (P= 1.000). A single burr hole is as efficacious as a double burr hole in terms of relief of symptoms and recurrence, and it has a shorter duration of surgery.

Drain type after burr-hole drainage of chronic subdural hematoma in geriatric patients: a subanalysis of the cSDH-Drain randomized controlled trial.

Chronic subdural hematoma (cSDH) occurs more frequently in elderly patients, while older patient age is associated with worse postoperative outcome following burr-hole drainage (BHD) of cSDH. The cSDH-Drain trial showed comparable recurrence rates after BHD and placement of either a subperiosteal drain (SPD) or subdural drain (SDD). Additionally, an SPD showed a significantly lower rate of infections as well as iatrogenic parenchymal injuries through drain misplacement. This post hoc analysis aims to compare recurrence rates and clinical outcomes following BHD of cSDH and the placement of SPDs or SDDs in elderly patients. The study included 104 patients (47.3%) 80 years of age and older from the 220 patients recruited in the preceding cSDH-Drain trial. SPDs and SDDs were compared with regard to recurrence rate, morbidity, mortality, and clinical outcome. A post hoc analysis using logistic regression, comparing the outcome measurements for patients < 80 and ≥ 80 years old in a univariate analysis and stratified for drain type, was further completed. Patients ≥ 80 years of age treated with an SDD showed higher recurrence rates (12.8%) compared with those treated with an SPD (8.2%), without a significant difference (p = 0.46). Significantly higher drain misplacement rates were observed for patients older than 80 years and treated with an SDD compared with an SPD (0% vs 20%, p = 0.01). Comparing patients older than 80 years to younger patients, significantly higher overall mortality (15.4% vs 5.2%, p = 0.012), 30-day mortality (3.8% vs 0%, p = 0.033), and surgical mortality (2.9% vs 1.7%, p = 0.034) rates were observed. Clinical outcome at the 12-month follow-up was significantly worse for patients ≥ 80 years old, and logistic regression showed a significant association of age with outcome, while drain type had no association with outcome. The initial findings of the cSDH-Drain trial and the findings of this subanalysis suggest that SPD may be warranted in elderly patients. As opposed to drain type, patient age (> 80 years) was significantly associated with worse outcome, as well as higher morbidity and mortality rates.

Brainstem Bleed after Chronic Subdural Hematoma Drainage

AbstractChronic subdural hematoma (CSDH) is one of the most frequent benign neurosurgical pathologies. Burr hole drainage is known to be safe, with low-morbidity and low-mortality rates. However, postoperative complications have been reported. We report the case of a 40-year-old lady who suffered a fatal brain stem hemorrhage after burr hole drainage for unilateral chronic SDH. Rapid decompression or sudden increase in cerebral blood flow were the probable factors for her brainstem bleed. Therefore, a slow rate of evacuation of CSDHs and maintenance of a correct blood pressure perioperatively are recommended to prevent serious complications.

Tricompartmental, Remote Intracerebral Hemorrhages Following Drainage of a Unilateral Chronic Subdural Hematoma: An Appraisal of the Pathogenesis

AbstractIntracerebral hemorrhage is a rare and unanticipated complication after burr hole drainage of a chronic subdural hematoma and usually occurs on the same side as the hematoma. In the absence of bleeding diathesis, iatrogenic injury or hypertension, it is commonly attributed to sudden expansion of the compressed brain, following rapid and uncontrolled removal of the subdural hematoma. Other factors like differential expansion of the various intracranial contents, abrupt changes in hemispheric balance, precipitous increase in focal cerebral blood flow, and unforeseen increase in cerebral venous pressure consequent to faulty positioning may also contribute to the pathogenesis of this complication.

Drain type and technique for subdural insertion after burr hole evacuation of chronic subdural hematoma.

Strengths and limitations of subdural versus subperiosteal drain location after burr hole evacuation of chronic subdural hematoma (CSDH) are currently debated. The safety of subdural placement of a drain has been questioned in a recent study by Soleman et al. from 2019, showing a misplacement rate of 17%, and these results have been further highlighted by the same authors, with a slightly lower misplacement rate of 15.8%, in the recent paper "When the drain hits the brain." The safety of subdural drainage for CSDH depends to a high degree on type of drain and surgical technique. In this technical note, we describe drain type and technique for drain placement which is standardized in Denmark.

Predictors of acute intracranial hemorrhage and recurrence of chronic subdural hematoma following burr hole drainage

BackgroundTo investigate predictors of postoperative acute intracranial hemorrhage (AIH) and recurrence of chronic subdural hematoma (CSDH) after burr hole drainage.MethodsA multicenter retrospective study of patients who underwent burr hole drainage for CSDH between January 2013 and March 2019.ResultsA total of 448 CSDH patients were enrolled in the study. CSDH recurrence occurred in 60 patients, with a recurrence rate of 13.4%. The mean time interval between initial burr hole drainage and recurrence was 40.8 ± 28.3 days. Postoperative AIH developed in 23 patients, with an incidence of 5.1%. The mean time interval between initial burr hole drainage and postoperative AIH was 4.7 ± 2.9 days. Bilateral hematoma, hyperdense hematoma and anticoagulant drug use were independent predictors of recurrence in the multiple logistic regression analyses. Preoperative headache was an independent risk factor of postoperative AIH in the multiple logistic regression analyses, however, intraoperative irrigation reduced the incidence of postoperative AIH.ConclusionsThis study found that bilateral hematoma, hyperdense hematoma and anticoagulant drug use were independently associated with CSDH recurrence. Clinical presentation of headache was the strongest predictor of postoperative AIH, and intraoperative irrigation decreased the incidence of postoperative AIH.

When the Drain Hits the Brain

The insertion of a subdural drain (SDD) after burr-hole drainage of chronic subdural hematoma (cSDH) was shown to reduce recurrence rate and improve outcome at 6 months. However, studies analyzing the rate of drain misplacement and complications associated with drain misplacement are sparse. We analyzed retrospectively a cohort of consecutive patients undergoing burr-hole drainage for cSDH in 2 institutes. Drain type (subperiosteal drain vs. SDD), drain misplacement rate, and drain-associated complications were analyzed. We explored potential risk factors for drain misplacement and associated complications in the SDD subgroup using univariate and multivariate analysis. Drain misplacement was defined as incorrect drain position exceeding the subdural cavity and was categorized into drain misplacement without radiologic sequelae, drain misplacement causing radiologically confirmed iatrogenic bleeding, and drain misplacement causing neurologic symptoms. Of 463 included patients, 290 (62.6%) received an SDD. Drain misplacement occurred in 73 patients (15.8%). In 5 (6.9%) and 9 (12.3%) of these patients, iatrogenic bleeding and neurologic symptoms occurred, respectively. Intake of vitamin K antagonists (odds ratio [OR], 3.64) or different oral anticoagulants (OR, 10.24), and low preoperative Glasgow Coma Scale score (OR, 7.81) remained associated risk factors for drain misplacement after multivariate analysis. Patients with misplaced drains showed a strong association with postoperative bleeding (OR, 5.81), longer operation time (OR, 1.01), and hospitalization time (OR, 1.08) after multivariate analysis. The occurrence of SDD misplacement is unignorable, because it leads to iatrogenic drain-associated complications and seems to affect bleeding events and hospitalization time of patients undergoing burr-hole drainage of cSDH.

Take it seriously or not: postoperative pneumocephalus in CSDH patients?

Background: Pneumocephalus is a common finding after burr-hole drainage of chronic subdural hematoma (CSDH). Its effects have not been specifically studied.Methods: A retrospective analysis was performed in 140 patients with CSDH with single burr-hole drainage. The pre- and postoperative volumes of intracranial hematoma and the postoperative volume of pneumocephalus were calculated and analyzed with their relationships with Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) scores.Results: The preoperative hematoma volume and the patient ages are positively correlated with the 1-day postoperative pneumocephalus volume (p < 0.001, p < 0.01). There is no correlation between postoperative pneumocephalus volume and GCS/GOS scores (p > 0.05) and there is no difference of GCS/GOS scores or CSDH recurrence rate between patients with and without pneumocephalus (p > 0.05). The age and the volume of 1-day postoperative pneumocephalus are positively correlated with the absorbing rate of pneumocephalus (p < 0.01, p < 0.001).Conclusions: The pneumocephalus at a certain range has no effect on the prognosis of patients with CSDH and requires no specific intervention due to its self-absorbing capacity in the normal progress after surgery.HighlightsNo correlation between postoperative pneumocephalus volume and GCS/GOS scores.No difference of GCS/GOS or recurrence between patients with pneumocephalus or not.Pneumocephalus at certain range has no effect on the prognosis of patients.

Effect of Antithrombotic Therapy on Development of Acute Subdural Hematoma After Burr Hole Drainage of Chronic Subdural Hematoma.

To evaluate the relationship between the time from cessation of anticoagulant/antiplatelet medication to surgery and risk of postoperative acute subdural hematoma (ASDH) after burr hole drainage of chronic subdural hematoma (CSDH). A retrospective study of patients who underwent burr hole drainage of CSDH between December 2014 and December 2019 was performed. Demographic and clinical data regarding age, gender, medication (antithrombotic therapy), smoking, daily alcohol consumption, history of head trauma, presenting symptoms, and neurological examination were collected from the medical records. Patients were divided into 3 groups based on time from referral to surgery: < 24 hours, 24?72 hours, and > 72 hours. One hundred seventeen patients underwent burr hole drainage of CSDH during the 5-year study period. Seventy-two patients were male (61.5%) and 45 were female (38.5%). Mean age was 70.5 ± 7.2 years. Postoperative ASDH occurred in 2 of the 32 patients (6.3%) who were not taking antithrombotic medication and 6 of the 85 patients (7.1%) who were taking antithrombotic medication. The difference was not significant (p=0.797). The risk of ASDH after burr hole drainage of CSDH was not affected by antithrombotic medication. Although the literature suggests that antiplatelet and anticoagulant drugs to be discontinued between 5 and 7 days before surgery, our results showed that acute hemorrhage was not detected in any patient who underwent surgery more than 72 hours after referral.

In Reply: Subperiosteal vs Subdural Drain After Burr-Hole Drainage of Chronic Subdural Hematoma: A Randomized Clinical Trial (cSDH-Drain-Trial).

In Reply: Subperiosteal vs Subdural Drain After Burr-Hole Drainage of Chronic Subdural Hematoma: A Randomized Clinical Trial (cSDH-Drain-Trial).

Recuperación de pacientes en postoperatorio de drenaje de hematoma subdural crónico asociado al uso de ácido tranexámico

Con el objetivo de evaluar la recuperación de pacientes que recibieron ácido tranexámico luego del drenaje de hematoma subdural crónico (HSC), se seleccionan al azar 22 pacientes de ambos sexos en edades comprendidas de 32 a 87 años. A un grupo de 11 paciente intervenidos, se les continuó el tratamiento con la colocación de un sistema de drenaje externo tipo Jackson-Pratt (grupo A) y un segundo grupo de pacientes, se les continuó tratamiento con Ácido Tranexámico (grupo B). Ambos grupos fueron evaluados en aspectos clínicos y tomográficos una semana después de la intervención. La distribución obtenida por género representó 99,5% masculino. Del total de pacientes, la mitad presentó HSC en el lado derecho y los casos bilaterales representaron 31,8%. Los resultados funcionales postoperatorio fueron satisfactorios en el 59,1% comparado con los obtenidos en la escala Glasgow preoperatorio donde más del 50% de los casos no superaban el valor 13 de la escala. El síntoma más común fue hemiparesia izquierda (45,5%), seguido de hemiparesia derecha (22,7%). El tratamiento con Ácido Tranexámico obtuvo resultados satisfactorios en el 63,6% de los casos de manera inmediata y en el 27,3% a las 24 horas; caso contrario a los resultados obtenidos con el sistema de Jackson-Pratt, donde el 54,5% obtuvo mejoría a las 24 horas. De igual manera la relación entre días de hospitalización y tratamiento fue significativa. Estos resultados permiten concluir queel tratamiento con Ácido Tranexámico ofrece una excelente tasa de recuperación, con menor número de complicaciones, mortalidad y secuelas, permitiendo también disminuir el tiempo de permanencia hospitalaria.

Letter: Subperiosteal vs Subdural Drain After Burr-Hole Drainage of Chronic Subdural Hematoma: A Randomized Clinical Trial (cSDH-Drain-Trial)

Letter: Subperiosteal vs Subdural Drain After Burr-Hole Drainage of Chronic Subdural Hematoma: A Randomized Clinical Trial (cSDH-Drain-Trial)

Does Drain Position and Duration Influence Outcomes in Patients Undergoing Burr-Hole Evacuation of Chronic Subdural Hematoma? Lessons from a UK Multicenter Prospective Cohort Study.

BackgroundDrain insertion following chronic subdural hematoma (CSDH) evacuation improves patient outcomes.ObjectiveTo examine whether this is influenced by variation in drain location, positioning or duration of placement.MethodsWe performed a subgroup analysis of a previously reported multicenter, prospective cohort study of CSDH patients performed between May 2013 and January 2014. Data were analyzed relating drain location (subdural or subgaleal), position (through a frontal or parietal burr hole), and duration of insertion, to outcomes in patients aged >16 yr undergoing burr-hole drainage of primary CSDH. Primary outcomes comprised modified Rankin scale (mRS) at discharge and symptomatic recurrence requiring redrainage within 60 d.ResultsA total of 577 patients were analyzed. The recurrence rate of 6.7% (12/160) in the frontal subdural drain group was comparable to 8.8% (30/343) in the parietal subdural drain group. Only 44/577 (7.6%) patients underwent subgaleal drain insertion. Recurrence rates were comparable between subdural (7.7%; 41/533) and subgaleal (9.1%; 4/44) groups (P = .95). We found no significant differences in discharge mRS between these groups. Recurrence rates were comparable between patients with postoperative drainage for 1 or 2 d, 6.4% and 8.4%, respectively (P = .44). There was no significant difference in mRS scores between these 2 groups (P = .56).CONCLUSIONDrain insertion after CSDH drainage is important, but position (subgaleal or subdural) and duration did not appear to influence recurrence rate or clinical outcomes. Similarly, drain location did not influence recurrence rate nor outcomes where both parietal and frontal burr holes were made. Further prospective cohort studies or randomized controlled trials could provide further clarification.

Prophylactic Use of Antiepileptic Drug (Phenytoin) in Preventing Early Postoperative Seizure in Patients with Chronic Subdural Hematoma: A Randomized Control Trial

Abstract Introduction Antiepileptic drug (AED) therapy has been used prophylactically in various centers in patients with chronic subdural hematoma (CSDH) after surgical evacuation, although the benefit is unclear. Materials and Methods In this randomized controlled trial, patients with CSDH undergoing burr hole drainage were enrolled into two groups—one which received prophylactic phenytoin and the other without the drug use. Their clinical presentation, imaging findings and postoperative complications were analyzed. Primary objective of the study was to assess the efficacy of phenytoin in the reduction of early postoperative seizure. Results A total of 54 patients were enrolled in the study and randomized into two groups. Twenty-seven patients were assigned into the phenytoin group while another 27 patients to the “no phenytoin” group. Analysis of all patients in the no phenytoin group and those in the phenytoin group with therapeutic serum phenytoin levels were done. The incidence of postoperative seizure was 5.7%; and all patients who had seizures were in the no phenytoin group. This, however, was not statistically significant (p = 0.262). Two out of 25 patients on phenytoin (8%) developed adverse drug reactions. Conclusion Incidence of postoperative seizure in patients undergoing burr hole drainage for CSDH was low. Routine prophylactic use of AED, did not reduce seizure in early postoperative period.

Time to and Possible Risk Factors for Recurrence after Burr-hole Drainage of Chronic Subdural Hematoma: A Subanalysis of the cSDH-Drain Randomized Controlled Trial

The randomized controlled Chronic Subdural Hematoma (cSDH)-Drain-Trial showed comparable recurrence rates after placing a subperiosteal drain (SPD) or a subdural drain (SDD) for surgically drained cSDH, although SDD was associated with higher rates of infection and iatrogenic brain injury. This subanalysis examines the time to recurrence and possible risk factors for recurrence after burr-hole drainage of cSDH and placement of a SPD compared with a SDD. We included 220 patients from the preceding cSDH-Drain-Trial. Time to recurrence was compared within the 2 groups using a univariate Cox proportional hazards model. Apart from intraoperative brain expansion (iBE), defined by residual hematoma-cavity on computer tomography 24 hours after surgery, other possible pre-, intra- and postoperative risk factors for recurrence were assessed through univariate and multivariate analysis. Median time to recurrence was 22.5 days (interquartile range: 9.25-52 days, range: 0-81) showing no difference between the 2 groups. Less iBE (P= 0.019), lower Glasgow Outcome Scale score at discharge (P= 0.007), and lower Glasgow Coma Scale score at 24 hours (P= 0.037) were strongly associated with recurrence on univariate analysis. After multivariate logistic analysis, less iBE (odds ratio: 1.10, 95% CI: 1.01; 1.21; P= 0.03) remained the only significant risk factor associated with recurrence. When comparing the risk factors within the 2 groups, less iBE and lower Glasgow Outcome Scale score at release were associated with recurrence only in the SDD group. The inserted drain type after burr-hole drainage of cSDH does not seem to influence time to recurrence. SPD may be warranted in routine clinical practice, independent of individual patient, surgical, or hematoma characteristics.

In Reply to ”Cerebral Hyperperfusion Syndrome After Chronic Subdural Hematoma Drainage”

In Reply to ”Cerebral Hyperperfusion Syndrome After Chronic Subdural Hematoma Drainage”

Variation of Ventricular Size after Surgical Treatment of Chronic Subdural Hematoma.

Background:Surgical removal is the treatment of choice for chronic subdural hematoma (CSDH). Despite clinical improvement after surgery, computed tomography (CT) scan control often showed residual collection, which may discuss the possibility of failed surgery. The aim of this study is the assessment of ventricular size before and after surgery and to study its relation with residual hematoma.Methods:In this prospective study (2013-2016), 63 patients who had burr-hole drainage of CSDH were sequentially allocated to either two groups; Group 1 with CT scan control under the 3rd day of surgery and Group 2 with delayed CT scan control (from 4th to 7th day). Linear measure of ventricular size was assessed by Evans’ index. We reviewed and analyzed the data between both groups.Results:There were 33 patients in Group 1 and 30 patients in Group 2. Preoperatively, the average thickness of hematoma was 20.5 mm in Group 1 versus 19.9 mm in Group 2 (P = 0.67); the mean midline shift was 8.5 mm in each group; Evans’ index was 26.7% in Group 1 and 27% in Group 2 (P = 0.7). Postoperatively, the mean thickness of the residual hematoma was 7.7 mm in Group 1 and 8.4 mm in Group 2 (P = 0.57); the mean midline shift was 3.3 mm in Group 1 and 1.9 mm in Group 2 (P = 0.08); Evan's index was 28.5% in Group 1 and 32.1% in Group 2 (P = 0.002).Conclusion:The adoption of Evans’ index, for assessing the variation of ventricular size after surgery, by neurosurgeons appears to be a good and simple method for evaluation and following the success of surgical removal of CSDH, despite the observation of some residual collection in early CT scan control.

Low-dose aspirin and burr-hole drainage of chronic subdural hematoma: study protocol for a randomized controlled study

BackgroundLow-dose acetylsalicylic acid (ASA) in patients with chronic subdural hematoma (cSDH) represents a significant neurosurgical challenge. While continuation of ASA during the perioperative phase might increase recurrence and bleeding rates, discontinuation increases the risk of thromboembolic events. The aim of this study is to compare the postoperative recurrence and cardiovascular complication rates of patients undergoing burr-hole trepanation for cSDH with and without discontinuation of ASA.MethodsIn this prospective randomized, placebo-controlled, double-blinded study we include all patients undergoing burr-hole drainage of cSDH who are under ASA treatment. The patients are randomized into two groups, one receiving ASA and the other placebo perioperatively. The study primarily seeks to compare the rate of recurrent events under ASA to that under placebo treatment. Secondary objectives are thromboembolic event rate, perioperative blood loss, postoperative anemia, intra- and postoperative blood transfusion rate, and clinical outcome.DiscussionTo date, there is no evidence-based consensus on how to manage patients undergoing burr-hole drainage for cSDH who are under ASA treatment. Therefore, the decision to maintain or interrupt ASA treatment is based mostly on the surgeons’ preference. A randomized placebo-controlled study for this frequent question is urgently needed in order to provide class I evidence for the best possible treatment of this large group of patients.Trial registrationClinicalTrials.gov: NCT03120182. Initial Release: 19.04.2017. Study protocol: V2_23.02.2017