Association between pre-treatment perfusion profile and cerebral edema after reperfusion therapies in ischemic stroke

The relationship between reperfusion and edema is unclear, with experimental and clinical data yielding conflicting results. We investigated whether the extent of salvageable and irreversibly-injured tissue at baseline influenced the effect of therapeutic reperfusion on cerebral edema. In a pooled analysis of 415 patients with anterior circulation large vessel occlusion from the Tenecteplase-versus-Alteplase-before-Endovascular-Therapy-for-Ischemic-Stroke (EXTEND-IA TNK) part 1 and 2 trials, associations between core and mismatch volume on pre-treatment CT-Perfusion with cerebral edema at 24-hours, and their interactions with reperfusion were tested. Core volume was associated with increased edema (p < 0.001) with no significant interaction with reperfusion (p = 0.82). In comparison, a significant interaction between reperfusion and mismatch volume (p = 0.03) was observed: Mismatch volume was associated with increased edema in the absence of reperfusion (p = 0.009) but not with reperfusion (p = 0.27). When mismatch volume was dichotomized at the median (102 ml), reperfusion was associated with reduced edema in patients with large mismatch volume (p < 0.001) but not with smaller mismatch volume (p = 0.35). The effect of reperfusion on edema may be variable and dependent on the physiological state of the cerebral tissue. In patients with small to moderate ischemic core volume, the benefit of reperfusion in reducing edema is related to penumbral salvage.     

Current State of Evidence for Neuroimaging Paradigms in Management of Acute Ischemic Stroke

Stroke is the chief differential diagnosis in patient presenting to the emergency room with abrupt onset focal neurological deficits. Neuroimaging, including non-contrast computed tomography (CT), magnetic resonance imaging (MRI), vascular and perfusion imaging, is a cornerstone in the diagnosis and treatment decision-making. This review examines the current state of evidence behind the different imaging paradigms for acute ischemic stroke diagnosis and treatment, including current recommendations from the guidelines. Non-contrast CT brain, or in some centers MRI, can help differentiate ischemic stroke and intracerebral hemorrhage (ICH), a pivotal juncture in stroke diagnosis and treatment algorithm, especially for early window thrombolytics. Advanced imaging such as MRI or perfusion imaging can also assist making a diagnosis of ischemic stroke versus mimics such as migraine, Todd's paresis, or functional disorders. Identification of medium-large vessel occlusions with CT or MR angiography triggers consideration of endovascular thrombectomy (EVT), with additional perfusion imaging help identify salvageable brain tissue in patients who are likely to benefit from reperfusion therapies, particularly in the ≥6 h window. We also review recent advances in neuroimaging and ongoing trials in key therapeutic areas and their imaging selection criteria to inform the readers on potential future transitions into use of neuroimaging for stroke diagnosis and treatment decision making. ANN NEUROL 2024;95:1017–1034     

Carney Complex: case report and review

Carney complex is a very rare multiple neoplasia syndrome with cardiac, cutaneous, and neural tumours with a variety of pigmented lesion of skin. We are reporting a rare case of carney complex in which left atrial myxoma with superficial angiomyxoma, giant cell tumour of bone and lentigines showed a unique association. This patient underwent successful surgical excision of left atrial myxoma under cardiopulmonary bypass.     

The influence of obstetric intervention on trends in twin stillbirths: United States, 1989–99

Objective: Although twin stillbirth rates have declined substantially over the past two decades, the contribution of changes in obstetric interventions to reducing twin stillbirths has not been quantified.

Methods: We carried out a retrospective cohort study of twin live births and stillbirths in the United States between 1989 and 1999 (n?=?1?102?212). Changes in the rate of stillbirth (???22 weeks) before and after adjustment for changes in labor induction, Cesarean delivery and sociodemographic factors were estimated through ecological logistic regression analysis. This analysis was based on aggregating data by each state within the United States.

Results: Between 1989 and 1999, rates of labor induction and Cesarean delivery among twin live births increased by 138% (from 5.8% to 13.8%) and 15% (from 48.3% to 55.6%), respectively. These changes were accompanied by a 43% decline in the stillbirth rate between 1989 and 1999 (from 24.4 to 13.9 per 1000 fetuses at risk). After excluding births weighing <?500?g, rates of labor induction among twins at 22–27 weeks', 28–33 weeks' and ??34 weeks' gestation increased by 95%, 131% and 127%, respectively, between 1989 and 1999. Cesarean delivery rates also increased by 55%, 29% and 2% in these same gestational age categories. The 48% (relative risk (RR) 0.52, 95% confidence interval (CI) 0.49–0.55) decline in stillbirth rate between 1989–91 and 1997–99 was reduced to a 25% (RR 0.75, 95% CI 0.72–0.79) decline after adjustment for changes in labor induction and Cesarean delivery. The decline in the rate of twin stillbirths was larger at later gestational ages (at ??32 and ??34 weeks) where the largest absolute increases in labor induction rates were observed.

Conclusions: The use of Cesarean delivery and especially labor induction for twin pregnancies has increased substantially in the United States over the last decade and these changes have been associated with a large decline in the rate of stillbirth among twins.     

Comparative analysis of Shwachman‐Diamond syndrome to other inherited bone marrow failure syndromes and genotype–phenotype correlation

Hashmi SK, Allen C, Klaassen R, Fernandez CV, Yanofsky R, Shereck E, Champagne J, Silva M, Lipton JH, Brossard J, Samson Y, Abish S, Steele M, Ali K, Dower N, Athale U, Jardine L, Hand JP, Beyene J, Dror Y. Comparative analysis of Shwachman‐Diamond syndrome to other inherited bone marrow failure syndromes and genotype–phenotype correlation. Our knowledge of the phenotypes of inherited bone marrow failure syndromes (IBMFSs) derives from case reports or case series in which only one IBMFS was studied. However, the substantial phenotypic overlap necessitates comparative analysis between the IBMFSs. Shwachman–Diamond syndrome (SDS) is an IBMFS that the appreciation of what comprises its clinical phenotype is still evolving. In this analysis we used data on 125 patients from the Canadian Inherited Marrow Failure Study (CIMFS), which is a prospective multicenter population‐based study. Thirty‐four cases of SDS patients were analyzed and compared to other patients with the four most common IBMFSs on the CIMFS: Diamond Blackfan anemia, Fanconi anemia (FA), Kostmann/severe congenital neutropenia and dyskeratosis congenita (DC). The diagnosis of SDS, FA and DC was often delayed relative to symptoms onset; indicating a major need for improving tools to establish a rapid diagnosis. We identified multiple phenotypic differences between SDS and other IBMFSs, including several novel differences. SBDS biallelic mutations were less frequent than in previous reports (81%). Importantly, compared to patients with biallelic mutations, patients with wild type SBDS had more severe hematological disease but milder pancreatic disease. In conclusion, comprehensive study of the IBMFSs can provide useful comparative data between the disorders. SBDS‐negative SDS patients may have more severe hematological failure and milder pancreatic disease.     

Initial combination therapy with saxagliptin and metformin provides sustained glycaemic control and is well tolerated for up to 76 weeks

Aim: To assess the efficacy and safety of saxagliptin + metformin initial combination therapy compared with saxagliptin or metformin alone over 76 weeks (24‐week short‐term + 52‐week long‐term extension) in treatment‐naÏve type 2 diabetes mellitus patients with inadequate glycaemic control. Methods: In this phase 3, parallel‐group, double‐blind, active‐controlled study, 1306 patients 18–77 years of age (HbA1c 8.0–12.0%) were randomized to saxagliptin 5 mg + 500 mg metformin, saxagliptin 10 mg + 500 mg metformin, saxagliptin 10 mg + placebo or 500 mg metformin + placebo. Blinded metformin was titrated during weeks 1–5 of the short‐term treatment period in 500 mg/day increments to 2000 mg/day maximum in the metformin‐based treatment groups. No titration of metformin was permitted during the long‐term treatment period. A total of 888 patients completed the study (76 weeks), 613 without being rescued. Changes in HbA1c, fasting plasma glucose, 120‐min postprandial glucose (PPG) and PPG‐area under the curve (AUC) from baseline to week 76 were analysed using a repeated‐measures model. Results: At 76 weeks, adjusted mean changes from baseline HbA1c (95% CI) for saxagliptin 5 mg + metformin, saxagliptin 10 mg + metformin, saxagliptin 10 mg and metformin were ?2.31 (?2.44, ?2.18), ?2.33 (?2.46, ?2.20), ?1.55 (?1.70, ?1.40) and ?1.79% (?1.93, ?1.65), respectively (post hoc and nominal p < 0.0001 vs. metformin and saxagliptin monotherapies for saxagliptin 5 mg + metformin and saxagliptin 10 mg + metformin). The proportions of patients requiring rescue or discontinuation for insufficient glycaemic control were lower for saxagliptin + metformin than for either monotherapy. Little or no attenuation in PPG‐AUC or 120‐min PPG was observed between weeks 24 and 76 for saxagliptin + metformin, indicating persistent efficacy. Adverse event rates were similar across groups; hypoglycaemic events occurred at a low frequency. Conclusion: Saxagliptin + metformin initial combination therapy was well tolerated and produced sustained glycaemic control for up to 76 weeks, with greater improvements in glycaemic parameters compared with either drug alone.