European Academic Centers Research Articles

Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial

CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA. CASSIOPEIA was a two-part, open-label, phase 3 trial of patients done at 111 European academic and community-based centres. Eligible patients were aged 18-65 years with transplant-eligible newly diagnosed myeloma and an Eastern Cooperative Oncology Group performance status of 0-2. In part 1, patients were randomly assigned (1:1) to pre-transplant induction and post-transplant consolidation with D-VTd or VTd. Patients who completed consolidation and had a partial response or better were re-randomised (1:1) to intravenous daratumumab maintenance (16 mg/kg every 8 weeks) or observation for 2 years or less. An interactive web-based system was used for both randomisations, and randomisation was balanced using permuted blocks of four. Stratification factors for the first randomisation (induction and consolidation phase) were site affiliation, International Staging System disease stage, and cytogenetic risk status. Stratification factors for the second randomisation (maintenance phase) were induction treatment and depth of response in the induction and consolidation phase. The primary endpoint for the induction and consolidation phase was the proportion of patients who achieved a stringent complete response after consolidation; results for this endpoint remain unchanged from those reported previously. The primary endpoint for the maintenance phase was progression-free survival from second randomisation. Efficacy evaluations in the induction and consolidation phase were done on the intention-to-treat population, which included all patients who underwent first randomisation, and efficacy analyses in the maintenance phase were done in the maintenance-specific intention-to-treat population, which included all patients who were randomly assigned at the second randomisation. This analysis represents the final data cutoff at the end of the study. The trial is registered with ClinicalTrials.gov, NCT02541383. Between Sept 22, 2015 and Aug 1, 2017, 1085 patients were randomly assigned to D-VTd (n=543) or VTd (n=542); between May 30, 2016 and June 18, 2018, 886 were re-randomised to daratumumab maintenance (n=442) or observation (n=444). At the clinical cutoff date, Sept 1, 2023, median follow-up was 80·1 months (IQR 75·7-85·6) from first randomisation and 70·6 months (66·4-76·1) from second randomisation. Progression-free survival from second randomisation was significantly longer in the daratumumab maintenance group than the observation-alone group (median not reached [95% CI 79·9-not estimable (NE)] vs 45·8 months [41·8-49·6]; HR 0·49 [95% CI 0·40-0·59]; p<0·0001); benefit was observed with D-VTd with daratumumab maintenance versus D-VTd with observation (median not reached [74·6-NE] vs 72·1 months [52·8-NE]; 0·76 [0·58-1·00]; p=0·048) and VTd with daratumumab maintenance versus VTd with observation (median not reached [66·9-NE] vs 32·7 months [27·2-38·7]; 0·34 [0·26-0·44]; p<0·0001). The long-term follow-up results of CASSIOPEIA show that including daratumumab in both the induction and consolidation phase and the maintenance phase led to superior progression-free survival outcomes. Our results confirm D-VTd induction and consolidation as a standard of care, and support the option of subsequent daratumumab monotherapy maintenance, for transplant-eligible patients with newly diagnosed multiple myeloma. Intergroupe Francophone du Myélome, Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research & Development.

Overcoming barriers to career progression for mid-career female physician-scientists: Insights and solutions

Background Gender equity in academia is a significant challenge. To investigate career advancement perspectives of mid-career female physician-scientists, identify their needs and barriers, and develop a mentor-sponsorship strategy to improve their representation in higher academic ranks. Methods In this qualitative study, conducted at a Western European academic medical center, we interviewed 19 mid-career female physician-scientists across all specialties, including radiology. Data were analyzed using thematic analysis. Results Four themes were identified: 1. Horizontal and vertical ambitions, (i.e., knowledge expansion and hierarchical advancement) 2. Evaluation of talent, 3. Career path needs, and 4. Receiving support. These themes revealed barriers to women's advancement, including limited talent recognition, inadequate leadership support, self-limiting beliefs, structural issues, and lack of networking opportunities. To address these challenges, a mentor-sponsorship program should prioritize sponsor training, start immediately at the beginning of the mid-career phase (attainment of assistant professorship), emphasize horizontal and vertical development, take work-life balance into account, establish mentor networks, and allow individuals to choose mentors and sponsors based on their needs and aspirations. Conclusions This study has identified key needs and barriers that impede the advancement of female physician-scientists in academia. To address these challenges, a tailored mentor-sponsorship program is recommended. Key program elements include training leadership to recognize talent and offer proactive support, starting at the onset of the mid-career phase, emphasizing horizontal and vertical development, and establishing a strong mentor-sponsor network with thoughtful matching. These actions can help to overcome obstacles and facilitate the progress of women in academia.

Individualized center-based analysis of urinary and sexual functional outcome after radical prostatectomy based on the prostate cancer outcome study: a post hoc pathway to patient outcome measurement analysis for quality improvement.

We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center. All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution. Logistic regression analyses were performed to examine the correlation between individual surgeons, patient characteristics, patient clinical data, and their urinary continence and sexual function. In total, data of 429 men were analyzed: unstratified mean (SD) EPIC-26 domain score for urinary function decreased from 93.3 (0.7) to 60.4 (1.5) one year after RPE, respectively for sexual function from 64.95 (1.6) to 23.24 (1.1). Patients with preoperative adequate urinary function (EPIC-26 score > 80) reported significantly different mean urinary function scores between 53.35 (28.88) and 66.25 (25.15), p= 0.001, stratified by surgeons experience. On binary logistic regression analyses, only nerve sparing techniques (OR: 1,83, 95% CI: 1.01;3.21; p = 0.045) and low body mass index (OR: 0.91, CI: 0.85;0.99, p= 0.032) predicted adequate postoperative urinary function. The results show how using provider-specific data from a larger cohort study enables to develop institution-specific analysis for functional outcomes after RPE. These models can be used for internal quality improvement as well as enhanced and provider-specific patient communication and shared decision making.

Legal Historians of Russian Diaspora in 1920s—1930s

The article characterizes the activities and legacy of Russian legal historians who found themselves in emigration in European academic centers in the 1920s. Among these researchers are mentioned M. N. Yassinsky, G. V. Demchenko, F. V. Taranovsky, A. V. Soloviev, and M. V. Shakhmatov. It is shown that prior to the revolution, these scholars taught at various universities in Russia, and in emigration they occupied chairs at higher educational institutions in Yugoslavia and Czechoslovakia. The sources of the study include published works by the scholars, memoirs of emigrants, as well as archival materials of various types from storage facilities in Russia and Slovenia, which are being introduced into scholarly circulation for the first time. The analysis of sources revealed that their establishment in emigration was associated with certain difficulties. On the other hand, the experience gained in Russian universities in studying and teaching the history of Russian and Slavic law helped them integrate into the local academic environment. Only Taranovsky and Shakhmatov to some extent adhered to their previous themes in their scholarly activities, while other scholars changed theirs. It is concluded that this was due to a lack of access to sources and the demands of the courses being taught. At the same time, it is emphasized that there was ideological-methodological unity and awareness of belonging to a particular scientific community. The conclusion is drawn that pre-revolutionary schools of legal history continued to exist in the conditions of European emigration.

Acute kidney injury in patients undergoing endovascular or open repair of juxtarenal or pararenal aortic aneurysms

BackgroundThe aim of this cohort study was to report the proportion of patients who develop periprocedural acute kidney injury (AKI) after endovascular repair (ER) and open surgery (OS) in patients with juxta/pararenal abdominal aortic aneurysm and to assess potential risk factors for AKI. The study also aimed to report the short- and long-term outcomes of patients with and without AKI. MethodsThis was a multicenter cohort study of five European academic high-volume centers (>50 OS or 50 ER infrarenal AAA repairs, plus >15 complex AAA repairs per year). All consecutively treated patients were extracted from a prospective vascular surgical registry and the data were scrutinized retrospectively. The primary end point for this study was the development of AKI. AKI was diagnosed when there is a two-fold increase of serum creatinine or decrease of glomerular filtration rate of >50% within 1 week of AAA repair. Secondary end points included long-term mortality and end-stage renal disease (ESRD). ResultsAKI occurred in 16.6% of patients in the ER group vs 30.3% in the OS group (P < .001). The 30-day mortality rate was higher among patients with AKI in both ER (15.4% vs 3.1%; P = .006) and OS (13.2% vs 5.3%; P = .001) groups. Age, chronic kidney disease, presence of significant thrombus burden in the pararenal region, >1000 mL blood loss in ER group were associated with development of AKI. Age, diabetes mellitus, chronic kidney disease, presence of significant thrombus burden in the pararenal region, and a proximal clamping time of >30 minutes in the OS group were associated with the development of AKI, whereas renal perfusion during clamping was the protective factor against AKI development. After a median follow-up of 91 months, AKI was associated with higher mortality rates in both the ER group (58.9% vs 29.7%; P < .001) and the OS group (61.5% vs 27.3%; P < .001). After the same follow-up period, AKI was associated with a higher incidence of ESRD in both the ER group (12.8% vs 3.6%; P = .009) and the OS group (9.9% vs 2.9%; P < .001). ConclusionsThe current study identified important pre and postoperative factors associated with AKI after juxta/pararenal abdominal aortic aneurysm repair. Patients with postoperative AKI had significantly higher short- and long term mortality and higher incidence of ESRD than patients without AKI.

Endovascular Repair of Juxtarenal and Pararenal Abdominal Aortic Aneurysms Using a Novel Low-Profile Fenestrated Custom-Made Endograft: Technical Details and Short-Term Outcomes.

The aim of this study is to share preliminary experiences and outcomes with a novel custom-made fenestrated TREO® Abdominal Stent-Graft System to treat juxtarenal and pararenal abdominal aortic aneurysms (AAAs). Juxtarenal and pararenal AAA patients treated with the custom-made fenestrated TREO® Abdominal Stent-Graft System were included from 4 high-volume European academic medical centers from June 2021 to September 2023. Technical success and 30-day/in-hospital mortality and complications were analyzed. Technical success was defined as successful endovascular implantation of the stent graft with preservation of antegrade flow to the target vessels, and absence of type 1 or 2 endoleak (EL) at the first postoperative computed tomography angiography (CTA). Forty-two consecutive patients were included. The majority of the devices were constructed with 2 (N=4; 9.5%), 3 (N=9; 21.4%), or 4 (N=27; 64%) fenestrations. In 1 case, the device was constructed with a single fenestration (2.4%) and 1 device contained 5 fenestrations (2.4%); 17% had previous AAA repair. Target vessel cannulation with placement of a bridging stent was successful in all but 1 vessel (99, 3%). One aneurysm-related death occurred in the direct postoperative period and 2 limb occlusions necessitated reintervention during admission. In the median follow-up period of 101 (2-620) days, 3 more patients died due to non-aneurysm-related causes. Technical success was achieved in 90% of the cases. Nineteen ELs were seen on the first postoperative CT scan: 1 type 1b EL (N=1; 2%), 15 type 2 ELs (N=15; 36%), and 3 type 3 ELs (N=3%). Eleven patients received more than 1 CT scan during a median follow-up of 361 days (82-620): 3 type 2 ELs resolved and 1 type 3 EL was treated in this period. In the follow-up, 1 patient had a coagulation disorder that caused occlusions of the branches. The results of the first experiences using the custom-made fenestrated TREO® Abdominal Stent-Graft System in Europe are promising. There was a low short-term mortality and morbidity rate in these patients of which 17% had previous AAA repair. Mid-term and long-term follow-up data are needed to evaluate endograft durability and performance. This study shows the first experiences and short-term results of a novel low-profile custom-made device: the custom-made fenestrated TREO® Abdominal Stent-Graft System. Showing these results and experiences can help the physicians in clinical decision-making for their patients.

Patients' attitude with surgery for Peyronie's disease: results from a multicentric European study.

Despite the existence of conservative therapies for Peyronie's disease (PD), surgery is commonly utilized for the treatment of bothersome curvatures due to its potential effectiveness, although it carries intrinsic risks and may not universally lead to satisfactory outcomes. To explore the rate and factors influencing patients' willingness to undergo surgery for PD. Data were prospectively collected in 5 European academic centers between 2016 and 2020. Data included age, time from PD onset, penile pain, curvature degree, difficulty at penetration, hourglass deformity, erectile dysfunction (ED), and previous treatments. All patients were offered conservative treatments, either medications or injections. Tunical shortening or lengthening procedures were offered as an alternative to conservative treatments, when indicated. Penile prosthesis was offered to those with concomitant ED. Patients' attitudes with surgery were recorded. Logistic regression analyses tested the profile of patients who were more likely to be willing to undergo surgery. Patients' willingness to undergo surgery for PD. This study included 343 patients with a median age of 57.3years (IQR, 49.8-63.6) and a median penile curvature of 40.0° (IQR, 30.0°-65.0°). Overall, 161 (47%) experienced penetration difficulties and 134 (39%) reported ED. Additionally, hourglass deformity and penile shortening were reported by 48 (14%) and 157 (46%), respectively. As for previous treatments, 128 (37%) received tadalafil once daily; 54 (16%) and 44 (13%), intraplaque verapamil and collagenase injections; and 30 (9%), low-intensity shock wave therapy. Significant curvature reduction (≥20°) was observed in 69 (20%) cases. Only 126 (37%) patients were open to surgery for PD when suggested. At logistic regression analysis after adjusting for confounders, younger age (odds ratio [OR], 0.97; 95% CI, 0.95-1.00; P = .02), more severe curvatures (OR, 1.04; 95% CI, 1.03-1.06; P < .0001), and difficulty in penetration (OR, 1.88; 95% CI, 1.04-3.41; P = .03) were associated with a greater attitude to consider surgical treatment. The need for effective nonsurgical treatments for PD is crucial, as is comprehensive patient counseling regarding surgical risks and benefits, particularly to younger males with severe curvatures. Main limitations are the cross-sectional design and the potential neglect of confounding factors. Patients with PD, having a lower inclination toward surgery, emphasize the need for effective nonsurgical alternatives and accurate counseling on the risks and benefits of PD surgery, particularly for younger men with severe curvatures.

Reduction of cardiac allograft vasculopathy by PCI: Quantification and correlation with outcome after heart transplantation

Abstract Background Percutaneous coronary intervention (PCI) might improve outcome of heart transplanted (HTx) patients at severe stages of cardiac allograft vasculopathy (CAV). Yet, risk stratification of HTx patients after PCI remains challenging. The International Society for Heart and Lung Transplantation (ISHLT) provides a nomenclature for CAV classification that does not include patients after PCI (1). It is unclear how to define an individual optimal CAV reduction and how to stratify patients with CAV after PCI. Besides, whether risk-stratification tools of non-transplanted patients apply to HTx patients with CAV is uncertain. Purpose To assess whether the ISHLT CAV classification remains prognostic after PCI, and whether risk stratification models of non-transplanted patients can be applied to HTx patients with CAV. Methods At two European academic centers, 203 patients were stratified according to CAV severity and PCI history, and patients were assigned to only one cohort: cohort 1 (ISHLT CAV grade 1, without PCI, n=126) or cohort 2 (ISHLT CAV grades 2&amp;3, with PCI). At first diagnosis of CAV or first PCI, respectively, ISHLT CAV grades, SYNTAX scores I and II (SXS-I and SXS-II) were used to quantify baseline and residual CAV (rISHLT, rSXS-I, rSXS-II). A rSXS-I&amp;gt;0 defined incomplete revascularization (IR). Five-year mortality was assessed. For cohort 2, first reintervention was a secondary outcome. Baseline parameters were also included into analysis. Results SXS-II predicted mortality in cohort 1 (Hazard ratio [HR] 2.5 [1.4–4.8], p=0.004), whereas SXS-I (HR 4.2 [1.4–12.2], p=0.009) and SXS-II (HR 7.1 [2.0–24.5], p=0.002) predicted mortality in cohort 2. Post-PCI, IR (HR 5.4 [1.7–17.0], p=0.004), high rISHLT (HR 3.6 [1.3–10.2], p=0.02) and highest tertile of rSXS-II (HR 5.1 [1.6–15.9], p=0.006) were associated with higher mortality. In cohort 2, post-transplant interval and KDIGO category of renal function at timepoint 0 were also predictors of 5-year mortality after first PCI (HR 1.1 [1.0 – 1.2], p=0.004 and HR 4.5 [1.8–11.3], p=0.01, respectively). In bivariable Cox analysis, baseline SXS-II, IR, rSXS-II, post-transplant interval and KDIGO category of renal function remained predictors of 5-year mortality. The interval to first reintervention was inversely related to baseline SXS-I (r=-0.55, p&amp;lt;0.001) and rSXS-I (r=-0.50, p=0.003). Conclusion A higher reduction of stenotic CAV was associated with improved 5-year survival rate after first PCI. ISHLT CAV classification could apply for risk stratification after PCI and SYNTAX-scores could be complemental for risk stratification and individualization of invasive follow-up of HTx patients with CAV.Figure 1.Study flow chart.Figure 2.Kaplan-Meier curves (cohort 2)

Persistent flow inside the Woven EndoBridge at angiographic follow-up: A multicenter study.

The occurrence of persistent intra-device filling (BOSS 1, using the Bicêtre Occlusion Scale Score (BOSS)) in aneurysms treated with a Woven Endobridge (WEB) device is infrequent based on angiographic follow-up. To date, three monocentric case series were published studying BOSS 1 cases. Through a multicenter retrospective study, we aimed to report the incidence, and risk factors of intra-WEB persistent filling. We reached out to European academic centers that treat patients using WEB devices and requested de-identified data of patients treated with a WEB device and underwent angiographic follow-up, at least 3 months after embolization, to assess the BOSS 1 occlusion score. We compared baseline characteristics, treatment modalities, and aneurysm data of the included BOSS 1 patients with those of a control group consisting of non-BOSS 1 patients (n = 116) who had an available angiographic follow-up. Univariable and multivariable models were employed for analysis. Among the pooled sample of 591 aneurysms treated with WEB, the rate of persistent flow (BOSS 1) at angiographic follow-up was 5.2% (n = 31 out of 591), performed after an average of 8.7 ± 6.3 months. In the multivariable-adjusted analysis, dual antiplatelet therapy in the postoperative period (adjusted odds ratio [aOR] 4.3 [95% CI 1.3-14.2]), and WEB undersizing (aOR 10.8 [95% CI 2.9-40]) were independently associated with a BOSS 1 persistent flow result. Persistent blood flow within the WEB device during angiographic follow-up (BOSS 1) is an uncommon occurrence. Our findings indicate that post-procedural dual antiplatelet therapy and undersizing of the WEB device are independently associated with the presence of BOSS 1 at follow-up.

Application of clinical and molecular profiling data to improve patient outcomes in psoriatic arthritis.

Achieving a good outcome for a person with Psoriatic Arthritis (PsA) is made difficult by late diagnosis, heterogenous clinical disease expression and in many cases, failure to adequately suppress inflammatory disease features. Single-centre studies have certainly contributed to our understanding of disease pathogenesis, but to adequately address the major areas of unmet need, multi-partner, collaborative research programmes are now required. HIPPOCRATES is a 5-year, Innovative Medicines Initiative (IMI) programme which includes 17 European academic centres experienced in PsA research, 5 pharmaceutical industry partners, 3 small-/medium-sized industry partners and 2 patient-representative organizations. In this review, the ambitious programme of work to be undertaken by HIPPOCRATES is outlined and common approaches and challenges are identified. It is expected that, when completed, the results will ultimately allow for changes in the approaches to diagnosing, managing and treating PsA allowing for better short-term and long-term outcomes.

Excessive Sedation as a Risk Factor for Delirium: A Comparison between Two Cohorts of ARDS Critically Ill Patients with and without COVID-19.

Excessive sedation is associated with poor outcome in critically ill acute respiratory distress syndrome (ARDS) patients. Whether this prognostic effect varies among ARDS patients with and without COVID-19 has yet to be determined. We compared the prognostic value of excessive sedation-in terms of delirium, length of stay in intensive care unit (ICU-LOS) and ICU mortality-between COVID-19 and non-COVID-19 critically ill ARDS patients. This was a second analysis of prospectively collected data in four European academic centers pertaining to 101 adult critically ill ARDS patients with and without COVID-19 disease. Depth of sedation (DOS) and delirium were monitored through processed electroencephalogram (EEG) and the Confusion Assessment Method for ICU (CAM-ICU). Our main exposure was excessive sedation and how it relates to the presence of delirium, ICU-LOS and ICU mortality. The criterion for excessive sedation was met in 73 (72.3%) patients; of these, 15 (82.2%) and 58 (69.1%) were in non-COVID-19 and COVID-19 ARDS groups, respectively. The criteria of delirium were met in 44 patients (60.3%). Moreover, excessive sedation was present in 38 (86.4%) patients with delirium (p &lt; 0.001). ICU death was ascertained in 41 out of 101 (41.0%) patients; of these, 37 (90.2%) had excessive sedation (p &lt; 0.001). The distribution of ICU-LOS among excessive-sedated and non-sedated patients was 22 (16-27) vs. 14 (10.5-19.5) days (p &lt; 0.001), respectively. In a multivariable framework, excessive sedation was independently associated with the development of delirium (p = 0.001), increased ICU mortality (p = 0.009) and longer ICU-LOS (p = 0.000), but only in COVID-19 ARDS patients. Independent of age and gender, excessive sedation might represent a risk factor for delirium in COVID-19 ARDS patients. Similarly, excessive sedation shows to be an independent predictor of ICU-LOS and ICU mortality. The use of continuous EEG-based depth of sedation (DOS) monitoring and delirium assessment in critically ill COVID-19 patients is warranted.

The VISICORT project: Lessons learned from solid organ transplantation

AbstractAims of the Presentation: (a) To summarize the rationale and research strategies for the VISICORT project. (b) To compare and contrast research approaches to understanding adverse immune responses to corneal and solid organ allo‐transplants.AbstractCorneal allo‐transplantation has been utilized for over 100 years to restore and improve vision in patients suffering from opacifying diseases of the cornea. Its development preceded that of solid organ transplantation and its worldwide frequency continues to exceed that of commonly‐transplanted organs including kidney, heart, liver and lung. The scope and success rates for corneal transplantation have evolved over time as a result of technical innovations, clinical practice developments and advances in eye banking. However, the impact of immunological complications, in particular acute rejection, on the long‐term functional survival of high‐risk corneal allografts has remained significant and the evidence base for specific immunosuppressive regimens to prevent rejection is limited. Strikingly, the large amount of elegant pre‐clinical research into the immunological response to corneal allografts has not been complemented by extensive studies of adverse immune responses in human recipients. Against this background, the VISICORT project was initiated in 2014 to bring together corneal transplant experts and investigators with expertise in solid organ transplantation, immunological profiling, proteomic analysis, regenerative therapies and biobanking to collaboratively address the challenge of better understanding adverse immune responses in human corneal transplantation.In this presentation, I will first summarize the strategies and designs for cross‐sectional and longitudinal clinical cohort studies of corneal allo‐transplant recipients at 5 European academic centres with collection of extensive clinical data and biological specimens including donor and recipient cornea, aqueous humour, tears, whole blood, serum, plasma and peripheral blood mononuclear cells. I will also describe the development of bespoke resources and protocols for the coordination of patient enrolment, data gathering and biospecimen processing, storage and transfer to a central biobank which underpinned the results to be described by other presenters in this session. Finally, I will discuss the extent to which the fields of corneal and solid organ transplantation have engaged in collaborative investigation prior to and during the course of the VISICORT project and reflect on the potential for such cross‐discipline research to advance towards the shared goal of preventing harmful allo‐immune responses and promoting donor‐specific tolerance.

The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI–neuropathology diagnostic accuracy study

Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. US National Institutes of Health (R01 AG26484).

PD23-07 PATIENTS' COMPLIANCE WITH SURGERY FOR PEYRONIE DISEASE: A MULTICENTRE EUROPEAN STUDY

You have accessJournal of UrologyCME1 May 2022PD23-07 PATIENTS' COMPLIANCE WITH SURGERY FOR PEYRONIE DISEASE: A MULTICENTRE EUROPEAN STUDY Paolo Capogrosso, Luigi Candela, Georgios Hatzichristodoulou, Juan I. Martinez Salamanca, Andrea Cocci, Marco Falcone, Edoardo Pozzi, Nicolò Schifano, Giorgio Ivan Russo, and Andrea Salonia Paolo CapogrossoPaolo Capogrosso More articles by this author , Luigi CandelaLuigi Candela More articles by this author , Georgios HatzichristodoulouGeorgios Hatzichristodoulou More articles by this author , Juan I. Martinez SalamancaJuan I. Martinez Salamanca More articles by this author , Andrea CocciAndrea Cocci More articles by this author , Marco FalconeMarco Falcone More articles by this author , Edoardo PozziEdoardo Pozzi More articles by this author , Nicolò SchifanoNicolò Schifano More articles by this author , Giorgio Ivan RussoGiorgio Ivan Russo More articles by this author , and Andrea SaloniaAndrea Salonia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002565.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Surgery still remains the most effective treatment for Peyronie Disease (PD), despite different conservative therapies have been suggested over time. However, surgical procedures are associated with a non-negligible risk of complications and failures. We investigated patients’ willingness of being operated for PD. METHODS: Data of PD patients were prospectively collected in 5 different European academic centers between 2016 and 2020. Baseline data included age, time from PD onset, penile pain, curvature degree, difficulty at penetration, hour-glass deformity, erectile dysfunction (ED) and previous treatments. All patients were offered conservative treatments, including either oral therapy or topical injections. Tunical shortening or lengthening procedures were offered as an alternative to conservative treatments, when indicated. Penile prosthesis implantation was offered to those with concomitant ED. Patients compliance with surgery was recorded. Logistic regression analyses tested the profile of patients who were more likely to comply with surgery. RESULTS: Data were available for 343 patients. Median (IQR) age was 57.3 (49.8, 63.6) years. Median curvature was 40.0° (30.0, 65.0); of all, 48 (14%) patients had concomitant hour-glass deformity and 157 (46%) reported penile shortening. Difficulty at penetration and ED were reported by 161 (47%) and 134(39%) patients, respectively. Overall, 128 (37%) patients had been treated with tadalafil once daily for no less than 12 months; 54 (16%) received verapamil injections; 30 (9%) ESWT; and, 44 (13%) CCH injections. A significant improvement (defined as a curvature reduction≥20°) was reported in 69 (20%) cases. Overall, only 37% (126) patients were willing to undergo surgery for PD. Younger patients (OR:0.97, 95%CI: 0.95, 1.00; p=0.02), patients with more severe curvatures (OR:1.04; 95%CI: 1.03, 1.06 ; p=<0.0001) and patients reporting difficulties at penetration (OR: 1.88; 95%CI 1.04-3.41; p=0.03) were more likely to comply with surgery, after accounting for other clinical variables. CONCLUSIONS: Compliance to surgery is low among patients with PD, thus further stressing the urgent need for effective conservative treatments. Surgery should be comprehensively discussed with younger patients with a severe curvature. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e411 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Paolo Capogrosso More articles by this author Luigi Candela More articles by this author Georgios Hatzichristodoulou More articles by this author Juan I. Martinez Salamanca More articles by this author Andrea Cocci More articles by this author Marco Falcone More articles by this author Edoardo Pozzi More articles by this author Nicolò Schifano More articles by this author Giorgio Ivan Russo More articles by this author Andrea Salonia More articles by this author Expand All Advertisement PDF DownloadLoading ...

Заграничные командировки антиковедов, их содержание и модели построения маршрутов в конце XIX - начале XX в.

This article examines the overseas business trips of domestic antiquity researchers in pre-revolutionary Russia at the end of the 19th - beginning of the 20th centuries. For the professional development of a scholar of antiquity, the importance of foreign business trips was essential for a number of reasons. Firstly, during an overseas trip, future researchers received the opportunity to touch the materials of the epoch they were interested in while visiting museums, participating in archaeological excavations, and studying monuments. They could directly observe the places in which the historical events they were investigating took place and dive into the atmosphere and the spirit of these places. Secondly, contacts with the leading foreign professors from Germany, France, England, Italy were extremely important for young researchers. During such academic contacts, Russian researchers adopted new, advanced theories from foreign colleagues, and also mastered previously unknown methods of research and teaching work. This study was based on a wide range of sources, including sources of personal origin (letters, autobiographies), regulations governing the work of this institution, as well as obituaries of antiquity scholars who went to overseas business trips. As a result of the study, the author distinguished two models of building the routes for overseas business trips of antiquity researchers. The first model, which involved visiting leading European academic centers, was formed in the first half of the 19th century and was the most widespread until the 1880s. It was replaced by a “new” model, which suggested spending the entire period allotted for a business trip in the countries of classical antiquity rather than visiting advanced academic centers in Europe. Along with the change in the model of building routes, the content of such business trips changed significantly. If in the previous period the main occupation of antiquity scholars abroad was acquaintance with the achievements of foreign colleagues and studying with them, in the later period, it was participating in archaeological excavations, making independent archaeological discoveries, visiting local museums and monuments, conducting field work with representatives of European science in the form of equal cooperation. The emergence of a new model of building the routes for overseas business trips and its predominance at the time under consideration is due, first of all, to positive changes in our science. Achievements in the development of Russian classical studies by the end of the 19th century brought it to the level corresponding to European; therefore, there was no need to undergo additional postgraduate training with European professors. In this period of time, libraries of the capital's universities were better supplied with advanced scholarly literature, including latest foreign works.

Current trends in anesthetic depth and antinociception monitoring: an international survey.

Current trends in anesthetic depth (i.e., hypnosis) and antinociception monitoring are unclear. We thus aimed to determine contemporary perspectives on monitoring these components of anesthesia during general anesthesia. Participants received and responded anonymously to an internet-based international survey supported by the European Society of Anaesthesiology and Intensive Care. Comparisons, when applicable, were carried out using Chi2 analysis or Fischer's exact test. A total of 564 respondents, predominantly from Europe (80.1%), participated. There was a strong participation from Belgium (11.5%). A majority (70.9%) of anesthetists considered hypnotic monitoring important on most occasions to always. In contrast, a majority (62.6%) never or only occasionally considered antinociception monitoring important. This difference in the perceived importance of anesthetic depth versus antinociception monitoring was significant (p < 0.0001). A majority of respondents (70.1%) believed that guiding hypnosis and antinociception using these monitors would improve patient care on most occasions to always. Nonetheless, a substantial number of participants were unsure if hypnotic (23%) or antinociception (32%) monitoring were recommended and there was a lack of knowledge (58%) of any published algorithms to titrate hypnotic and/or antinociceptive drugs based on the information provided by the monitors.In conclusion,current trends in European academic centers prioritize anesthesia depth over antinociception monitoring. Despite an agreement among respondents that applying strategies that optimize anesthetic depth and antinociception could improve outcome, there remains a lack of knowledge of appropriate algorithms. Future studies and recommendations should focus on clarifying goal-directed anesthetic strategies and determine their impact on perioperative patient outcome.

An antipsychotic not marketed in U.S. led to greater improvement in trial

A head‐to‐head trial conducted at four European academic medical centers has found that the antipsychotic amisulpride was more efficacious than aripiprazole or olanzapine in reducing psychotic symptoms in patients with schizophrenia. Amisulpride is not marketed in the United States for the treatment of schizophrenia. Study results were published in the November 2020 issue of Lancet Psychiatry.

In Reply to the Letter to the Editor Regarding “COVID-19 Impact on Neurosurgical Practice: Lockdown Attitude and Experience of a European Academic Center”

In Reply to the Letter to the Editor Regarding “COVID-19 Impact on Neurosurgical Practice: Lockdown Attitude and Experience of a European Academic Center”

Letter to the Editor Regarding “COVID-19 Impact on Neurosurgical Practice: Lockdown Attitude and Experience of a European Academic Center”

Letter to the Editor Regarding “COVID-19 Impact on Neurosurgical Practice: Lockdown Attitude and Experience of a European Academic Center”

COVID-19 Impact on Neurosurgical Practice: Lockdown Attitude and Experience of a European Academic Center

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is an unprecedented challenge. Different models of reorganization have been described aiming to preserve resources and ensure optimal medical care. Limited clinical neurosurgical experience with patients with COVID-19 has been reported. We share organizational experience, attitudes, and preliminary data of patients treated at our institution.MethodsInstitutional guidelines and patient workflow are described and visualized. A cohort of all neurosurgical patients managed during the lockdown period is presented and analyzed, assessing suspected nosocomial infection risk factors. A comparative surgical subcohort from the previous year was used to investigate the impact on surgical activity.ResultsA total of 176 patients were admitted in 66 days, 20 of whom tested positive for COVID-19. Patients initially admitted to the neurosurgical ward were less likely to be suspected for a COVID-19 infection compared with patients admitted for critical emergencies, particularly with neurovascular and stroke-related diseases. The mortality of patients with COVID-19 was remarkably high (45%), and even higher in patients who underwent surgical intervention (77%). In addition to the expected decrease in surgical activity (–53%), a decrease in traumatic emergencies was noted.ConclusionsBy applying infection prevention and resource-sparing logistics measures shared by the international medical community, we were able to maintain essential neurosurgical care in a pandemic with controlled nosocomial infection risk. Special consideration should be given to medical management and surgical indications in patients infected with severe acute respiratory syndrome coronavirus 2, because they seem to show a problematic hemostatic profile that might result in an unfavorable clinical and surgical outcome.