Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial.

BACKGROUND: Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging. METHODS: This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed. FINDINGS: Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05]). INTERPRETATION: The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible. FUNDING: Australian National Health Medical Research Council; Boehringer Ingelheim.

Ontogeny of the human fetal, neonatal, and infantile basioccipital bone: Traditional and extended eigenshape geometric morphometric analysis.

The basioccipital bone is an essential developmental component to the occipital bone, occipital condyles, foramen magnum, clivus, and cranial base. The basioccipital bone joins each exoccipital bone with a basiexoccipital synchondrosis and the basisphenoid/sphenoid bone with a spheno-occipital synchondrosis. The basioccipital is found intermediate to the petrous temporal bones and forms the bilateral petrooccipital/petroclival fissures otherwise known as the petrooccipital complex. Thus, the basioccipital bone is a central component to the developing cranial base. Despite the importance of basioccipital development in cranial ontogeny, there has been limited study of basioccipital ontogeny. This study assessed 98 disarticulated human basioccipital bones from a perinatal population ranging in age-at-death from 5-months intrauterine to 5-months post-natal development. Size and shape of basioccipital bones were assessed with traditional and extended eigenshape geometric morphometric analysis. The results of this study demonstrate that the basioccipital bone grows in width at a faster rate than it grows in length. The maximum basioccipital width surpassed the midsagittal length at approximately 7-months intrauterine development. Canonical variate analysis revealed statistically significant shape change occurring from a relatively narrow/elongate (anterior-to-posterior) basiocciput shape with mild concavity at the foramen magnum in the fifth and sixth intrauterine months to a relatively broad/stout basiocciput shape with more pronounced concavity in the postnatal months. Likewise, growth rate in total length was greater than midsagittal length, demonstrating enlargement of concavity in the anterior foramen magnum over time. This report provides insight into cranial development and aids in estimating age-at-death among fetuses and infants.

Infraorbital foramen location in the pediatric population: A guide for infraorbital nerve block.

BACKGROUND: Infraorbital nerve blocks are often performed for the management of postoperative pain associated with cleft lip correction. Infraorbital nerve block procedures depend on the identification of the infraorbital foramen; however, there is little information regarding the infraorbital foramen location in the pediatric population. AIMS: The aim of this study was to identify the location of the infraorbital foramen in the pediatric population relative to a midpoint between the nasospinale and jugale. METHODS: The study assessed the location of 152 infraorbital foramina relative to a midpoint between the nasospinale and J on dry crania. Crania were from individuals ranging in age-at-death from 6-month fetal to 18 years. The population was subdivided into fetal/infant (≥6 months fetal age-<2 years), child (≥2-<12 years), and adolescent (≥12-≤18 years) groups for comparison. RESULTS: The average distance of the infraorbital foramen from the nasospinale-to-jugale midpoint was 1.55 ± 0.78 mm (Mean ± SD) in the fetal/infant group, 0.80 ± 0.91 mm in the child group, and 1.31 ± 1.68 mm in the adolescent group. Furthermore, infraorbital foramina tended to be located medial to the nasospinale-to-jugale midpoint in the fetal/infant population, directly upon or superomedial to the nasospinale-to-jugale midpoint in the child population, and directly upon or superior/superolateral to the nasospinale-to-jugale midpoint in the adolescent population. CONCLUSIONS: The infraorbital foramen was located within 2 mm, on average, from the nasospinale-to-jugale midpoint regardless of age group. Therefore, the nasospinale-to-jugale midpoint may serve as useful means of identifying the location of the infraorbital foramen in the pediatric population and aid in optimizing infraorbital nerve block procedures. The information in this report is valuable in general, but may be particularly useful in developing countries where there is a lack of ultrasound training and availability for health care providers; or places where infraorbital nerve block may be the sole anesthetic modality for cleft lip surgery, even among adolescent patients.

The Infraorbital Foramen Is Located Midway Between the Nasospinale and Jugale: Considerations for Infraorbital Nerve Block and Maxillofacial Surgery.

Identification of the infraorbital foramen is important in infraorbital nerve block and the prevention of iatrogenic injury of the infraorbital nerve in maxillofacial surgeries. This study assessed the location of 887 infraorbital foramina from 518 adult crania of varied sex and population. The study assessed the midpoint of a line segment spanning from nasospinale to jugale (NS-J) relative to the infraorbital foramen. The mean distance of the NS-J midpoint from the infraorbital foramen was 2.1 ±â€Š1.9 mm (mean ±â€ŠSD) with a mode of 0 mm (266:887; 30%). The NS-J midpoint was located in the same plane or inferior to the infraorbital foramen in 98.4% of sides (873:887). There were no significant differences between sexes, populations, or sides with regard to the NS-J midpoint to infraorbital foramen distance. The NS-J midpoint can be used to locate the infraorbital foramen in both females and males of varied populations regardless of craniofacial diversity. The results of this study will aid in infraorbital nerve block procedures and maxillofacial surgery.

Metopism: a Study of the Persistent Metopic Suture.

Metopism, the persistence of the metopic suture in adulthood, is a clinically significant radiographic finding. In addition to masquerading as a fracture of the frontal bone, a persistent metopic suture may be associated with other clinically significant anatomical variations including frontal sinus abnormalities. Several geographically and craniofacially distinct populations have yet to be assessed for the prevalence of metopism. This study aimed to determine the prevalence of metopic sutures in adult crania of diverse populations among which scant research exists. A total of 505 adult crania were examined for the presence of a metopic suture. A total of 13 (2.57%) demonstrated metopism. Among subpopulations, metopism was present in 8.06% (5:62) of European crania, 15.38% (2:13) of East Asian crania, 2.20% (2:91) of Egyptian crania, and 2.86% (1:35) of Bengali crania. Metopism was also found in 1 Chilean, Roman, and Tchuktchi cranium, respectively. Metopism was not seen in crania from individuals of African (non-Egyptian) descent (0:62), Peruvians (0:144), Malayans (0:23), or Mexicans (0:23). Among sexes, metopism was present in 3.77% (8:212) of females and 1.79% (5:279) of males. The prevalence of metopism differs between populations and sexes. The results of this study provide anthropological, developmental, and clinical insight with regard to metopism.

The size and shape of the foramen magnum in man.

BACKGROUND: The foramen magnum (FM) has garnered broad interest across the disciplines of anthropology, comparative anatomy, evolutionary biology, and clinical sciences. Most studies regarding the structure of the FM in humans have been intrapopulation morphometric studies rather than interpopulation morphologic studies. The few studies assessing the morphology of the foramen have utilized ambiguous and subjective descriptors to describe foraminal shape and are, consequently, difficult to reproduce. Therefore, detailed study of FM shape among craniofacially and geographically diverse populations through reproducible methods is warranted. OBJECTIVES: The aim of this study was to assess intersex and interpopulation differences in FM size and shape among diverse populations. MATERIALS AND METHODS: The study analyzed 152 FMs of varied sex and race via traditional and geometric morphometric methods. RESULTS AND CONCLUSIONS: The study demonstrates that, within each distinct population, the size of the FM is significantly larger in males than in females; however, there are no significant differences in the shapes of the foramina between sexes. However, when comparing different populations to one another, there are significant differences with regard to both the size and shape of the FM. This study also presents a new model of FM ontogeny. Specifically, the growth occurring between the anterior and posterior foraminal boundaries before 5 years of age predicts the ultimate shape of the adult FM.

Improving access to acute stroke therapies: a controlled trial of organised pre-hospital and emergency care.

OBJECTIVE: To assess the effectiveness of the PAST (Pre-hospital Acute Stroke Triage) protocol in reducing pre-hospital and emergency department (ED) delays to patients receiving organised acute stroke care, thereby increasing access to thrombolytic therapy. DESIGN: Prospective cohort study using historical controls. SETTING: Hunter Region of New South Wales, September 2005 to March 2006 (pre-intervention) and September 2006 to March 2007 (post-intervention). PARTICIPANTS: Consecutive patients presenting with acute stroke to a regional, tertiary referral hospital. INTERVENTION: PAST protocol, comprising a pre-hospital stroke assessment tool for ambulance officers, an ambulance protocol for hospital bypass for potentially thrombolysis-eligible patients, and pre-hospital notification of the acute stroke team. MAIN OUTCOME MEASURES: Proportion of patients who received intravenous tissue plasminogen activator (tPA), process of care time points (symptom onset to ED arrival, ED arrival to tPA treatment, and ED transit time), and clinical outcomes of patients treated with tPA. RESULTS: The proportion of ischaemic stroke patients treated with tPA increased from 4.7% (pre-intervention) to 21.4% (post-intervention) (P < 0.001). Time point outcomes also improved, with a reduction in median times from symptom onset to ED arrival from 150 to 90.5 min (P = 0.004) and from ED arrival to stroke unit admission from 361 to 232.5 minutes (P < 0.001). Of those treated with tPA, 43% had minimal or no disability at 3 months. CONCLUSIONS: Organised pre-hospital and ED acute stroke care increases patient access to tPA treatment, which is proven to reduce stroke-related disability.

Evaluating Burkholderia pseudomallei Bip proteins as vaccines and Bip antibodies as detection agents.

Burkholderia pseudomallei is a biothreat agent and an important natural pathogen, causing melioidosis in humans and animals. A type III secretion system (TTSS-3) has been shown to be critical for virulence. Because TTSS components from other pathogens have been used successfully as diagnostic agents and as experimental vaccines, it was investigated whether this was the case for BipB, BipC and BipD, components of B. pseudomallei's TTSS-3. The sequences of BipB, BipC and BipD were found to be highly conserved among B. pseudomallei and B. mallei isolates. A collection of monoclonal antibodies (mAbs) specific for each Bip protein was obtained. Most recognized both native and denatured Bip protein. Burkholderia pseudomallei or B. mallei did not express detectable BipB or BipD under the growth conditions used. However, anti-BipD mAbs did recognize the TTSS needle structures of a Shigella strain engineered to express BipD. The authors did not find that BipB, BipC or BipD are protective antigens because vaccination of mice with any single protein did not result in protection against experimental melioidosis. Enzyme-linked immunosorbent assay (ELISA) studies showed that human melioidosis patients had antibodies to BipB and BipD. However, these ELISAs had low diagnostic accuracy in endemic regions, possibly due to previous patient exposure to B. pseudomallei.