Analysing All-Optical Random Bit Sequences Using Gap-Based Approaches.

Quantum mechanical phenomena are revolutionizing classical engineering fields such as signal processing or cryptography. When randomness plays an important role, like in cryptography where random bit sequences guarantee certain levels of security, quantum mechanical phenomena allow new ways of generating random bit sequences. Such sequences have a lot of applications in the communication sector, e.g., regarding data transmission, simulation, sensors or radars, and beyond. They can be generated deterministically (e.g., by using polynomials, resulting in pseudo-random sequences) or in a non-deterministic way (e.g., by using physical noise sources like external devices or sensors, resulting in random sequences). Important characteristics of such binary sequences can be modelled by gap processes in conjunction with the probability theory. Recently, all-optical approaches have attracted a lot of research interest. In this work, an adaptation of the quantum key distribution setup is utilized for generating randomised bit sequences. The simulation results show that all-optically generated sequences very well resemble the theoretically ideal probability density characteristic. Additionally, an experimental optical setup is developed that confirms the simulation results. Furthermore, m-sequences show very promising results as well as Gold sequences. Additionally, the level of burstiness, i.e., the distribution of ones and zeros throughout the sequence, is studied for the different sequences. The results enable the finding that generator polynomials with concentrated non-zero coefficients lead to more bursty bit sequences.

Work-related smartphone use during off-job hours and work-life conflict: A scoping review.

Over recent decades the use of smartphones for work purposes has burgeoned both within and beyond working hours. The aim of the study was to conduct a scoping review to explore the association between the use of smartphone technology for work purposes in off-job hours with employees' self-reported work-life conflict. Arksey and O'Malley's methodological framework was adopted. Searches were conducted in PsycINFO, International Bibliography of the Social Sciences (IBSS), Academic Search Complete, ProQuest Central, Web of Science, ProQuest Theses, Emerald, Business Source Complete, ScienceDirect, Scopus, Google Scholar. Articles were eligible that reported on a sample of workers, were published in English between 1st January 2012 and 29th November 2023. The review was conducted and reported using a quality assessment checklist and PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews). Data charting and synthesis was undertaken narratively, using the framework approach and thematic analysis. Twenty-three studies were identified, conducted in nine countries. Nineteen studies (83%) showed a significant association between increased use of smartphone for work purposes in off job-hours and increased work-life conflict, with small-to-moderate effect sizes. This relationship was mediated by psychological detachment from work, and communication about family demands with one's supervisor. Moderators either strengthened or attenuated the relationship between use of smartphone for work purposes in off job-hours and increased work-life conflict. Findings suggest that smartphone use during off-job hours is likely to impact negatively on work-life conflict, which has implications for employee wellbeing. Managers could play a key role in clarifying expectations about after-hours availability, reducing job pressure, advocating psychological detachment from work in off-job hours where it is appropriate, and creating a workplace culture where communication about the interplay between work and home life is encouraged. The protocol is registered on the Open Science Framework (OSF) (https://doi.org/10.17605/OSF.IO/WFZU6).

Multicenter evaluation of mechanical thrombectomy for distal medium vessel occlusions with National Institute of Health Stroke Scale Scores ≥ 6 and ≤ 6.

BACKGROUND: While mechanical thrombectomy is considered standard of care for large vessel occlusions, scientific evidence to support treatment for distal and medium vessel occlusions remains scarce. PURPOSE: To evaluate feasibility, safety, and outcomes in patients with low National Institute of Health Stroke Scale scores undergoing mechanical thrombectomy for treatment of distal medium vessel occlusions. MATERIALS AND METHODS: Retrospective data review and analysis of prospectively maintained databases at 41 academic centers in North America, Asia, and Europe between January 2017 and January 2022. Characteristics and outcomes were compared between groups with low stroke scale score (≤ 6) versus and higher stroke scale scores (> 6). Propensity score matching using the optimal pair matching method and 1:1 ratio was performed. RESULTS: Data were collected on a total of 1068 patients. After propensity score matching, there were a total of 676 patients included in the final analysis, with 338 patients in each group. High successful reperfusion rates were seen in both groups, 90.2% in ≤ 6 and 88.7% in the > 6 stroke scale groups. The frequency of excellent and good functional outcome was seen more common in low versus higher stroke scale score patients (64.5% and 81.1% versus 39.3% and 58.6%, respectively). The 90-day mortality rate observed in the ≤ 6 stroke scale group was 5.3% versus 13.3% in the > 6 stroke scale group. CONCLUSION: Mechanical thrombectomy in distal and medium vessel occlusions, specifically in patients with low stroke scale scores is feasible, though it may not necessarily improve outcomes over IVT.

Dual Antiplatelet Non-Responder: Resistance to Clopidogrel and Ticagrelor.

Background: Dual antiplatelet therapy is often required for neurointerventional procedures, especially when a stent or flow diverter is placed in the cervical and intracranial vessels. Patients are usually started on aspirin and clopidogrel given the simplicity of the once daily regimen with reasonable cost. Unfortunately, about a third of patients do not show the desired antiplatelet response to clopidogrel and another agent needs to be introduced. Ticagrelor is a potent antiplatelet medication that has a favorable pharmacological profile and has emerged as a reliable alternative to clopidogrel in recent years. Despite ticagrelor non-responders being rare, they do exist, and identification of these patients is important. Results: A 74-year-old female was incidentally found to harbor a right posterior communicating aneurysm which was successfully treated electively with stent-assisted coiling. Platelet inhibition testing revealed non-responsiveness to Clopidogrel. Ticagrelor was initiated but the patient's platelet reactivity unit remained in the normal range. Management algorithms to maximize a patient's ticagrelor response by facilitating enteral absorption were applied but no platelet inhibition was achieved. The patient was eventually identified as a true ticagrelor non-responder. Conclusion: Resistance to antiplatelet medication can result in devastating complications with permanent neurological deficits. Ticagrelor non-responders are rare but do exist. Platelet inhibition testing should be part of the preprocedural workup for neurointerventions.

Multicenter early United States feasibility study and periprocedural safety of LVIS EVO for the treatment of unruptured intracranial aneurysms.

BACKGROUND: Stent development has focused recently on low-profile, self-expandable stents compatible with 0.0165 inch microcatheters. The LVIS EVO is the second-generation version of the Low-Profile Visualized Intraluminal Support (LVIS) with improved visibility and resheathability. The LVIS EVO underwent a limited premarket release (PMR) in December 2023. This study aims to report the early safety and feasibility experience with the LVIS EVO stent for the treatment of intracranial aneurysms in the United States (US). METHODS: This was a multicenter, retrospective, observational study evaluating patients who underwent treatment of an intracranial aneurysm with an LVIS EVO stent after the limited PMR. All physicians who had placed an LVIS EVO stent were asked to input their cases after institutional review board approval was obtained. The data were then sent to a single center for analysis. Any patient aged 18 years or older who underwent treatment of an intracranial aneurysm with a LVIS EVO stent in the US was included from the initial PMR in December 2023 until April 2024. Patient age (or ≤90 years old), sex, preoperative modified Rankin Scale (mRS), aneurysm location, aneurysm measurements, and information about preoperative antiplatelet management were all collected. Data on periprocedural complications, 30-day mortality, discharge mRS, and length of stay were also collected. RESULTS: Some 53 patients with 55 aneurysms underwent treatment with the LVIS EVO stent at 15 institutions. All aneurysms were unruptured. The most common location was the anterior communicating artery (35%) followed by the middle cerebral artery bifurcation (31%). All patients were on dual antiplatelet therapy. The average aneurysm size was 5.2 mm with a neck size of 3.7 mm. The smallest distal parent vessel size was 1.2 mm and 36% of stents were deployed in distal parent vessels <2 mm. All (100%) cases had successful deployment and the stent was repositioned in 10% of cases. A single stent was utilized in 91% of cases. Coils were placed in 48 cases (87.2%) and a microcatheter was jailed in 98% of those cases. Immediate Raymond Roy (RR) Class I occlusion was obtained in 33%, Class II in 22%, Class IIIa in 37%, and Class IIIb in 8% of cases. There were no delayed thromboembolic or hemorrhagic complications. CONCLUSIONS: The LVIS EVO is a braided, self-expanding, retrievable stent with enhanced visibility and smaller cell size. The drawn filled tube (DFT) technology results in improved visibility of the stent, allowing for more controlled stent positioning and visualization of vessel wall apposition. All cases in our series had complete neck coverage and good wall apposition. There were no thromboembolic or hemorrhagic complications.

I saw the swirl sign: Acute extravasation of blood within a hematoma.

The swirl sign is a finding on non-contrast computed tomography (CT) scans that represents an acute extravasation of blood into a hematoma filled with clotted blood. In it, a "swirl" of active bleeding within a body of acutely clotted blood is noted as a hypodense accumulation within a hyperdense fluid collection. Here, we describe a case in which a 35-year-old female presents unresponsive with a Glasgow Coma Scale score of 3 and is ultimately found to have a large frontal intraparenchymal hematoma with intraventricular extension and an area of low attenuation within the hyperattenuating fluid collection on CT, otherwise known as the swirl sign. This radiographic sign has been associated with hematoma expansion, worse clinical outcomes as measured by the Glasgow Outcome Scale, and higher mortality rates. As such, all patients suspected to have intracranial bleeds should have CT imaging done as soon as possible. When the swirl sign is identified on CT, providers are clued in to the risk of clinical deterioration and the urgent need for surgical evaluation.

I saw the 'puff of smoke' sign before it vanished into thin air.

Moyamoya is characterized as a non-atherosclerotic and non-inflammatory vasculopathy that leads to progressive stenosis of the intracranial internal carotid arteries as well as the Circle of Willis. While it can be idiopathic (Moyamoya disease) or associated with another condition (Moyamoya syndrome), there is a characteristic 'puff of smoke' sign that can be appreciated on cerebral angiography.

Predicting drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors and forward planning.

INTRODUCTION: Cyclin-dependent kinase (CDK) 4/6 inhibitors are cornerstones in the treatment of Hormone Receptor (HR) positive and Human Epidermal Growth factor (HER2) negative metastatic breast cancer. Given their widespread use in the metastatic setting and emerging use in the adjuvant setting, studying drug-drug interactions (DDI) of these medications is of utmost importance. AREAS COVERED: This review provides key background information on the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. We discuss drug-drug interactions including those with proton pump inhibitors as well as CYP3A substrates, inhibitors, and inducers. We describe the effect of these drugs on membrane transporters and their substrates as well as those drugs that increase risk of CDK4/6 toxicities. Finally, we explore future directions for strategies to minimize drug-drug interactions. EXPERT OPINION: It is crucial to be mindful of medications that may interfere with drug absorption, such as proton pump inhibitors, as well as those that interfere with drug metabolism, such as CYP3A4 inhibitors and inducers. Additionally, special consideration should be given to populations at higher risk for polypharmacy, such as older patients with greater comorbidities. These interactions and patient characteristics should be considered when developing individual treatment plans with CDK4/6 inhibitors.

The Impact of Preprocedural Platelet Function Testing on Periprocedural Complication Rates Associated With Pipeline Flow Diversion: An International Multicenter Study.

BACKGROUND AND OBJECTIVES: Dual antiplatelet therapy (DAPT) is necessary to minimize the risk of periprocedural thromboembolic complications associated with aneurysm embolization using pipeline embolization device (PED). We aimed to assess the impact of platelet function testing (PFT) on reducing periprocedural thromboembolic complications associated with PED flow diversion in patients receiving aspirin and clopidogrel. METHODS: Patients with unruptured intracranial aneurysms requiring PED flow diversion were identified from 13 centers for retrospective evaluation. Clinical variables including the results of PFT before treatment, periprocedural DAPT regimen, and intracranial complications occurring within 72 h of embolization were identified. Complication rates were compared between PFT and non-PFT groups. Differences between groups were tested for statistical significance using the Wilcoxon rank sum, Fisher exact, or χ 2 tests. A P -value <.05 was statistically significant. RESULTS: 580 patients underwent PED embolization with 262 patients dichotomized to the PFT group and 318 patients to the non-PFT group. 13.7% of PFT group patients were clopidogrel nonresponders requiring changes in their pre-embolization DAPT regimen. Five percentage of PFT group [2.8%, 8.5%] patients experienced thromboembolic complications vs 1.6% of patients in the non-PFT group [0.6%, 3.8%] ( P = .019). Two (15.4%) PFT group patients with thromboembolic complications experienced permanent neurological disability vs 4 (80%) non-PFT group patients. 3.7% of PFT group patients [1.5%, 8.2%] and 3.5% [1.8%, 6.3%] of non-PFT group patients experienced hemorrhagic intracranial complications ( P > .9). CONCLUSION: Preprocedural PFT before PED treatment of intracranial aneurysms in patients premedicated with an aspirin and clopidogrel DAPT regimen may not be necessary to significantly reduce the risk of procedure-related intracranial complications.

Quality Improvement Methodology to Improve Standardized Reporting of Pediatric Thyroid Ultrasounds Using TI-RADS.

BACKGROUND/PURPOSE: The process of evaluating pediatric thyroid nodules at our institution was inconsistent with a high rate of negative biopsies raising concern of appropriate patient selection for biopsy. Our aim was to institute a standardized risk stratification reporting system for thyroid nodules to increase utilization and agreement of TI-RADS reporting at our institution. METHODS: Radiology report data were collected and analyzed as part of a quality improvement project. A standardized TI-RADS dictation template was created, ultrasound technicians were trained, a multi-disciplinary conference initiated, and education provided for radiologists and clinicians. Control charts were used to track utilization and agreement of scoring of TI-RADS reporting based upon review by a radiologist trained in TI-RADS scoring. RESULTS: From January 2019 to January 2021, 218 patients with a thyroid nodule had a thyroid ultrasound performed at our institution. TI-RADS was utilized in 0 % (0 of 57) of children in the four months prior to project initiation. Following creation of the template, utilization increased to 65 % (39 of 60) over 5 months. Utilization further increased after the first training conference and was maintained above 90 % for 13 months. Ultrasound reports were in agreement in 46.7 % (28 of 60) of children initially. Agreement in reporting improved to 71.4 % (10 of 14) in the 3 months following the first training and to 78.4 % (58 of 74) over 12 months. Agreement in reporting was maintained at 80 % in the following 6 months. CONCLUSIONS: A quality improvement initiative can improve utilization and agreement of scoring using the TI-RADS system in pediatrics. This may ultimately reduce unnecessary biopsies and sedation in children. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Quality Improvement.

Fluid-attenuated inversion-recovery sequence with fat suppression as an alternative to contrast-enhanced MRI in pediatric synovitis.

BACKGROUND: Non-contrast magnetic resonance imaging (MRI) fluid-attenuated inversion-recovery sequence (FLAIR) with fat suppression (FS) has not been validated in children. OBJECTIVE: Compare FLAIR to T1-weighted post contrast (T1CE) in the detection of knee synovitis. METHODS AND MATERIALS: Institutional review board (IRB) waived consent. Children who underwent T1CE and FLAIR sequences of the knee on a 3-T magnet from April 2021 to December 2021 were included. Two pediatric radiologists assessed axial FLAIR and T1CE images for synovitis and synovial thickness. Reliability and agreement were assessed. Sensitivities, specificities, and accuracy were calculated for FLAIR using T1CE as reference standard. RESULTS: In total, 42 knees (39 patients) were assessed (median age 12.9 years (2.3-17.8 years); 62% male, 38% female). Readers judged 20/42 (48%) knees to have synovitis. Sensitivity of FLAIR for reader 1 was 79% (19/24; 95% CI 0.58, 0.93) and 84% (16/19; 95% CI 0.60, 0.97) for reader 2. Specificity of FLAIR for reader 1 was 94% (17/18; 95% CI 0.73, 1) and 83% (19/23; 95% CI 0.61, 0.95) for reader 2. Accuracy for readers 1 and 2 was 86% (36/42; 95% CI 0.71, 0.95) and 83% (35/42; 95% CI 0.69, 0.93), respectively. Inter-reader reliability was good (0.75-0.90) for synovial measurements for FLAIR (ICC = 0.80; 95% CI 0.71, 0.86) and moderate for T1 CE (ICC = 0.62 (95% CI 0.48, 0.73)). CONCLUSION: FLAIR FS depicts synovium in the pediatric knee with similar reliability to T1 CE and may be an acceptable alternative to contrast in the initial diagnosis of synovitis.

Migrated coronary stent into the left internal carotid artery: a rescue technique.

Coronary stent dislodgement and migration is a rare phenomenon that can potentially result in life-threatening complications. We encountered the unusual case of a coronary artery stent that stripped from its delivery balloon and embolised into the left internal carotid artery during percutaneous coronary intervention. Such an event is a stressful experience for the interventional cardiologist but also an uncommonly encountered situation for a neurointerventionalist whose expertise may be sought to help navigate the situation. Planning the interventional approach and taking into consideration the tools available as well as potential complications is crucial to maximise the chances of best possible outcome for the patient. We were able to retrieve the stent safely and successfully, but, at the same time, we were prepared to manage any adverse events in the best way possible.

Dissecting Aneurysm of the Posterior Cerebral Artery.

Posterior circulation aneurysms are more likely to rupture than those in the anterior circulation but also pose more of a challenge for endovascular treatment or neurosurgical clipping. Aneurysms arising from the posterior cerebral artery are rare; dissecting aneurysms are even rarer. Dissecting posterior cerebral artery aneurysms can be spontaneous or post traumatic. Our case depicts a patient with acute subarachnoid hemorrhage due to a ruptured, dissecting posterior cerebral artery aneurysm who underwent successful endovascular treatment by means of flow diversion.

I saw Medusa's head sign and turned to stone.

Developmental venous anomalies (DVAs) are characterized by many radially oriented medullary veins surrounding a central draining vessel. When the imaging plane is perpendicular to the central vessel, these medullary veins resemble Medusa's head of snakes. Medusa's head sign, or caput medusae, can be appreciated on contrast enhanced CT scans and MRIs of the brain and is highly indicative of a DVA.

Assessment of thrombectomy procedure difficulty by neurointerventionalists based on vessel geometry parameters from carotid artery 3D reconstructions.

BACKGROUND: Diagnosing and treating acute ischemic stroke patients within a narrow timeframe is challenging. Time needed to access the occluded vessel and initiate thrombectomy is dictated by the availability of information regarding vascular anatomy and trajectory. Absence of such information potentially impacts device selection, procedure success, and stroke outcomes. While the cervical vessels allow neurointerventionalists to navigate devices to the occlusion site, procedures are often encumbered due to tortuous pathways. The purpose of this retrospective study was to determine how neurointerventionalists consider the physical nature of carotid segments when evaluating a procedure's difficulty. METHODS: Seven neurointerventionalists reviewed 3D reconstructions of CT angiograms of left and right carotid arteries from 49 subjects and rated the perceived procedural difficulty on a three-point scale (easy, medium, difficult) to reach the targeted M1. Twenty-two vessel metrics were quantified by dividing the carotids into 5 segments and measuring the radius of curvature, tortuosity, vessel radius, and vessel length of each segment. RESULTS: The tortuosity and length of the arch-cervical and cervical regions significantly impacted difficulty ratings. Additionally, two-way interaction between the radius of curvature and tortuosity on the arch-cervical region was significant (p < 0.0001) wherein, for example, at a given arch-cervical tortuosity, an increased radius of curvature reduced the perceived case difficulty. CONCLUSIONS: Examining the vessel metrics and providing detailed vascular data tailored to patient characteristics may result in better procedure preparation, facilitate faster vessel access time, and improve thrombectomy outcomes. Additionally, documenting these correlations can enhance device design to ensure they suitably function under various vessel conditions.

Use of Real-World Evidence in a Virtual Bridging Analysis for a Human Epidermal Growth Factor Receptor 2-Targeted Antibody-Drug Conjugate in Gastric Cancer.

This study bridged pharmacokinetic, efficacy, and safety clinical trial data from Japan to a Western population using real-world evidence (RWE) to investigate the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in the treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. Using population pharmacokinetic and exposure-response (efficacy/safety) models, exposure-efficacy data from 117 patients and exposure-safety data from 158 patients in Japan who received T-DXd 6.4 mg/kg as second-line or later treatment were bridged to RWE including covariate information from 25 Western patients with HER2-positive gastric cancer who received second-line or later T-DXd treatment. Pharmacokinetic simulations indicated that intact T-DXd and released drug (DXd) steady-state exposures were comparable between Western patients and patients from Japan; the Western/Japan ratio of exposure medians ranged from 0.82 (T-DXd steady-state minimum concentration) to 1.18 (DXd steady-state maximum concentration). Exposure-efficacy simulations estimated a confirmed objective response rate of 28.6% (90% confidence interval, 20.8-38.4) in real-world Western patients versus 40.1% (90% confidence interval, 33.5-47.0) in patients from Japan, possibly because of checkpoint inhibitor use in 4% versus 30% of patients, respectively. Western patients had a higher estimated rate of serious adverse events than patients from Japan (42.2% vs 34.6%); however, the rate of interstitial lung disease was lower (less than 10%) in Western patients. Overall, T-DXd was predicted to have meaningful clinical activity and a manageable safety profile in Western patients with HER2-positive gastric cancer. Using RWE, bridging analysis supported US approval of T-DXd 6.4 mg/kg in advanced gastric cancer before a clinical trial was completed in Western patients.

Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study.

BACKGROUND: Approximately 15-20% of advanced gastric and gastro-oesophageal junction cancers overexpress HER2. In DESTINY-Gastric01, the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan improved response and overall survival versus chemotherapy in patients from Japan and South Korea with locally advanced or metastatic HER2-positive gastric or gastro-oesophageal junction cancer whose disease progressed after two lines of previous therapy including trastuzumab. Here, we report primary and updated analyses of the single-arm, phase 2 DESTINY-Gastric02 trial, which aimed to examine trastuzumab deruxtecan in patients living in the USA and Europe. METHODS: DESTINY-Gastric02 is a single-arm, phase 2 study in adult patients from 24 study sites in the USA and Europe (Belgium, Spain, Italy, and the UK). Eligible patients were aged at least 18 years and had an Eastern Cooperative Oncology Group performance status of 0 or 1, pathologically documented unresectable or metastatic gastric or gastro-oesophageal junction cancer, progressive disease on or after first-line therapy with a trastuzumab-containing regimen, with at least one measurable lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and centrally confirmed HER2-positive disease on a postprogression biopsy. Patients were given 6·4 mg/kg of trastuzumab deruxtecan intravenously every 3 weeks until disease progression, withdrawal by patient, physician decision, or death. The primary endpoint was confirmed objective response rate by independent central review. The primary endpoint and safety were assessed in the full analysis set (ie, participants who received at least one dose of study drug). Here, we report the primary analysis of this study, with a data cutoff of April 9, 2021, and an updated analysis, with a data cutoff of Nov 8, 2021. This trial is registered with ClinicalTrials.gov, NCT04014075, and is ongoing. FINDINGS: Between Nov 26, 2019, and Dec 2, 2020, 89 patients were screened and 79 were enrolled and subsequently treated with trastuzumab deruxtecan (median age 60·7 years [IQR 52·0-68·3], 57 [72%] of 79 were male, 22 [28%] were female, 69 [87%] were White, four [5%] were Asian, one [1%] was Black or African American, one [1%] was Native Hawaiian or Pacific Islander, one had missing race, and three [4%] were other races). At the primary analysis (median follow-up 5·9 months [IQR 4·6-8·6 months]), confirmed objective response was reported in 30 (38% [95% CI 27·3-49·6]) of 79 patients, including three (4%) complete responses and 27 (34%) partial responses, as assessed by independent central review. As of data cutoff for the updated analysis (median follow-up 10·2 months [IQR 5·6-12·9]), a confirmed objective response was reported in 33 (42% [95% CI 30·8-53·4]) of 79 patients, including four (5%) complete responses and 29 (37%) partial responses, as assessed by independent central review. The most common grade 3 or worse treatment-emergent adverse events were anaemia (11 [14%]), nausea (six [8%]), decreased neutrophil count (six [8%]), and decreased white blood cell count (five [6%]). Drug-related serious treatment-emergent adverse events occurred in ten patients (13%). Deaths determined to be associated with study treatment occurred in two patients (3%) and were due to interstitial lung disease or pneumonitis. INTERPRETATION: These clinically meaningful results support the use of trastuzumab deruxtecan as second-line therapy in patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer. FUNDING: Daiichi Sankyo and AstraZeneca.

Exploring three-body fragmentation of acetylene trication.

The three-body breakup of [C2H2]3+ formed in collision with Xe9+ moving at 0.5 atomic units of velocity is studied by using recoil ion momentum spectroscopy. Three-body breakup channels leading to (H+, C+, CH+) and (H+, H+, C2 +) fragments are observed in the experiment and their kinetic energy release is measured. The breakup into (H+, C+, CH+) occurs via concerted and sequential modes, whereas the breakup into (H+, H+, C2 +) shows only the concerted mode. By collecting events coming exclusively from the sequential breakup leading to (H+, C+, CH+), we have determined the kinetic energy release for the unimolecular fragmentation of the molecular intermediate, [C2H]2+. By using ab initio calculations, the potential energy surface for the lowest electronic state of [C2H]2+ is generated, which shows the existence of a metastable state with two possible dissociation pathways. A discussion on the agreement between our experimental results and these ab initio calculations is presented.

A multicenter retrospective study evaluating the impact of desmopressin on hematoma expansion in patients with antiplatelet-associated intracranial hemorrhage.

INTRODUCTION: Antiplatelet medications interfere with hemostasis which can contribute to increased risk of hematoma expansion and potentially worse outcomes in patients presenting with intracranial hemorrhages (ICH). Current Neurocritical Care Society guidelines recommend desmopressin (DDAVP) in patients with antiplatelet-associated ICH with evidence limited by small cohorts. MATERIALS AND METHODS: Patients were included in our multi-center, retrospective study if they had computed tomographic (CT) scan confirmed ICH and were taking antiplatelet medications. Patients were excluded if hospital length of stay was <24 h, administered DDAVP dose was <0.3 µg/kg, no follow-up head CT scan was performed within the first 24 h after baseline, major neurosurgical intervention was performed in between CT scans, or the injury was an acute on chronic ICH. The primary outcome was incidence of hematoma expansion (defined as >20 % increase from baseline). Secondary outcomes were incidence of thrombotic complications within 7 days, largest absolute decrease in serum sodium within the first 24 h, and patient disposition. RESULTS: Among the 209 patients included in the study, 118 patients received DDAVP while 91 did not. The frequency of hematoma expansion was similar between patients who received DDAVP and those who did not (16.1 % vs 17.6 %; P = 0.78). No difference in secondary outcomes was observed between the two groups. CONCLUSIONS: These findings in conjunction with recently published literature may suggest minimal benefit or harm with DDAVP treatment. However, further study could elucidate any potential impact on long-term function outcomes.