The association between perihaematomal oedema and functional outcome after spontaneous intracerebral haemorrhage: A systematic review and meta-analysis.

PURPOSE: Perihaematomal oedema (PHO) formation has gained increasing interest as a therapeutic target after spontaneous intracerebral haemorrhage (ICH). Whether PHO contributes to poor outcome is unclear. We aimed to determine the association between PHO and outcome in patients with spontaneous ICH. METHOD: We searched five databases up to 17 November 2021 for studies of ⩾10 adults with ICH reporting the presence of PHO and outcome. We assessed risk of bias, extracted aggregate data and used random effects meta-analysis to pool studies that reported odds ratios (OR) with 95% confidence intervals (CI). Primary outcome was poor functional outcome defined as modified Rankin Scale score of 3-6 at 3 months. Additionally, we assessed PHO growth and poor outcome at any time of follow-up. We prospectively registered the protocol in PROSPERO (CRD42020157088). FINDINGS: We identified 12,968 articles, of which we included 27 studies (n = 9534). Eighteen studies reported an association between larger PHO volume and poor outcome, six a neutral result and three an inverse relationship. Larger absolute PHO volume was associated with poor functional outcome at 3 months (OR per mL increase of absolute PHO 1.03, 95% CI 1.00-1.06, I2 44%, four studies). Additionally, PHO growth was associated with poor outcome (OR 1.04, 95% CI 1.02-1.06, I2 0%, seven studies). DISCUSSION: In patients with spontaneous ICH, larger PHO volume is associated with poor functional outcome at 3 months. These findings support the development and investigation of new therapeutic interventions targeting PHO formation to evaluate if reduction of PHO improves outcome after ICH.

Injury patterns of equine-related trauma: A fifteen-year review of hospital admissions to a level 1 trauma center.

OBJECTIVE: Little information exists about horse-related injury admissions to Level 1 trauma centers in the Western United States. This study describes injury patterns in this population, to reveal potential areas for injury prevention initiatives. METHODS: A retrospective database review of 512 non-fatal equine-related injuries over a 15-year period was conducted, using a Level 1 hospital trauma registry. To determine patterns of injury, patients injured by riding or being near a horse were classified according to age, sex, helmet use, abbreviated injury score, anatomical region injured, and length of stay. RESULTS: Equine-related injury was more frequent among females than males, the anatomical region most at risk among adults was the lower extremity (including pelvis), and among children and youth, the head. 75% of head-injured patients were not wearing a helmet at the time of injury and those with the most severe head injuries were least likely to be wearing a helmet. CONCLUSION: Preventable equine-related injuries occur across all ages, are more frequent among females, and affect all regions of the body. Despite head-injury risks associated with horse activities, helmet use was not common among most of the injured. Decreasing the risk of these injuries requires use of appropriate protective equipment and enhanced education campaigns aimed at those in the horse industry and the general public.

Design and Synthesis of a Ferrocene-Based Diol Library and Application in the Hetero-Diels-Alder Reaction.

Diol scaffolds have been utilized as highly effective catalysts and ligands in a wide range of catalytic asymmetric transformations. For scaffolds to be successful as broadly used motifs, they should be prepared cheaply through facile routes and be easily handled. Herein, the synthesis of a family of planar chiral diols based on a modular and robust three-step route is described, which yields catalytically active diols in >99 % de and >99 % ee, with up to seven different chiral elements. These diols have been characterized by X-ray crystallographic analysis, which provides clear evidence for the likely transition state when applied in the asymmetric hetero-Diels-Alder reaction. Without altering the stereochemistry of the catalyst backbone, it is possible to access both enantiomers of the product by varying the substitution of the catalyst at the α-position.

Scale-Up of a Rh-Catalyzed Asymmetric sp3-sp2 Suzuki-Miyaura-Type Reaction.

Csp2-Csp2 Suzuki-Miyaura couplings (SMCs) are ubiquitous in the synthesis of small molecules, but analogous Csp2-Csp3 bond-forming SMCs are rare, especially asymmetric variants. Recently, we developed a series of Rh-catalyzed couplings between racemic sp3-hybridized allyl chlorides and heteroaryl boronic acids. Here, we demonstrate that these catalytic asymmetric reactions can be scaled-up to give over 100 g of a product. The reaction we chose to test couples a heteroaromatic boronic acid derivative and a racemic bicyclic electrophile to give a product with three contiguous stereogenic centers. The SMC product was obtained as a single diastereomer in 90% yield and 98% ee. Kinetic analysis of the reaction reveals two exothermic steps in the reaction setup and revealed the means by which to prevent the generation of heat spikes detrimental to the stability of the catalyst.

A General Catalyst Controlled Route to Prostaglandin F2α.

We report a general, catalyst-controlled route to prostaglandin F2α and its analogues. The approach uses a Rh-catalyzed dynamic kinetic asymmetric Suzuki-Miyaura coupling reaction between a racemic bicyclic allyl chloride and alkenyl boronic esters bearing chiral alcohols to give cyclopentyl intermediates bearing 3 contiguous stereocenters. The route provides advanced intermediates in 99% ee as a single diastereoisomer in all cases examined, with the absolute stereochemistry of the cyclopentane core controlled by the ligand. Intermediates that could be used to produce prostaglandin analogues such as bimatoprost, latanoprost, fluprostenol, and cloprostenol were synthesized. The final two stereocenters were installed via Pd-catalyzed Tsuji-Trost alkylation and iodolactonization. The synthesis of PG F2α was achieved in 19% yield in 16 longest linear steps.

Association of baseline hematoma and edema volumes with one-year outcome and long-term survival after spontaneous intracerebral hemorrhage: A community-based inception cohort study.

BACKGROUND: Hospital-based studies have reported variable associations between outcome after spontaneous intracerebral hemorrhage and peri-hematomal edema volume. AIMS: In a community-based study, we aimed to investigate the existence, strength, direction, and independence of associations between intracerebral hemorrhage and peri-hematomal edema volumes on diagnostic brain CT and one-year functional outcome and long-term survival. METHODS: We identified all adults, resident in Lothian, diagnosed with first-ever, symptomatic spontaneous intracerebral hemorrhage between June 2010 and May 2013 in a community-based, prospective inception cohort study. We defined regions of interest manually and used a semi-automated approach to measure intracerebral hemorrhage volume, peri-hematomal edema volume, and the sum of these measurements (total lesion volume) on first diagnostic brain CT performed at ≤3 days after symptom onset. The primary outcome was death or dependence (scores 3-6 on the modified Rankin Scale) at one-year after intracerebral hemorrhage. RESULTS: Two hundred ninety-two (85%) of 342 patients (median age 77.5 y, IQR 68-83, 186 (54%) female, median time from onset to CT 6.5 h (IQR 2.9-21.7)) were dead or dependent one year after intracerebral hemorrhage. Peri-hematomal edema and intracerebral hemorrhage volumes were colinear (R2 = 0.77). In models using both intracerebral hemorrhage and peri-hematomal edema, 10 mL increments in intracerebral hemorrhage (adjusted odds ratio (aOR) 1.72 (95% CI 1.08-2.87); p = 0.029) but not peri-hematomal edema volume (aOR 0.92 (0.63-1.45); p = 0.69) were independently associated with one-year death or dependence. 10 mL increments in total lesion volume were independently associated with one-year death or dependence (aOR 1.24 (1.11-1.42); p = 0.0004). CONCLUSION: Total volume of intracerebral hemorrhage and peri-hematomal edema, and intracerebral hemorrhage volume alone on diagnostic brain CT, undertaken at three days or sooner, are independently associated with death or dependence one-year after intracerebral hemorrhage, but peri-hematomal edema volume is not. DATA ACCESS STATEMENT: Anonymized summary data may be requested from the corresponding author.

Recent developments in the synthesis and applications of chiral ferrocene ligands and organocatalysts in asymmetric catalysis.

With the ever-present need for novel asymmetric methodologies in organic synthesis to allow chemists to access enantiopure compounds, so too is there a need for new chiral ligands and organocatalysts to affect these transformations. Due to the unique properties of ferrocene and its derivatives, ferrocenyl compounds are unsurprisingly considered privileged structures in asymmetric catalysis. The versatility of the ferrocene moiety gives rise to a vast range of diverse ligand and catalyst motifs which are successful in broad ranges of mechanistically distinct reactions. This review details recent advances in the application of ferrocenyl mono-, bi- and tridentate-ligands and ferrocene-derived organocatalysts in asymmetric catalysis. Given the necessity for the development of new approaches to expand the scope of ferrocenyl ligands and catalysts, this review also illustrates the development of elegant and novel methodologies for the synthesis of ferrocenyl compounds.

Correction: Recent developments in the synthesis and applications of chiral ferrocene ligands and organocatalysts in asymmetric catalysis.

Correction for 'Recent developments in the synthesis and applications of chiral ferrocene ligands and organocatalysts in asymmetric catalysis' by Laura Cunningham et al., Org. Biomol. Chem., 2020, DOI: 10.1039/d0ob01933j.

Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells.

The design and first enantioselective synthesis of a series of chiral ferrocifens and ferrociphenols was realised by enantioselective palladium-catalysed intramolecular direct C-H bond activation followed by McMurry coupling. Biological evaluation revealed moderate anticancer activities on breast cancer cells and evidence of chiral discrimination between enantiomers. Treatment of the novel ferrocifens with Ag2 O revealed that these systems are unable to form a neutral quinone methide, yet still demonstrate marked antiproliferative properties against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 cell lines. This bioactivity arises from two mechanisms: Fenton-type chemistry and the anti-estrogenic activity associated with the tamoxifen-like structure.