SWI versus GRE-T2*: Assessing cortical superficial siderosis in advanced cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cortical superficial siderosis (cSS) is a key neuroimaging marker of cerebral amyloid angiopathy (CAA) detected on blood-sensitive magnetic resonance imaging (MRI). We aimed to assess cSS in advanced CAA patients and explore differences in its evaluation between susceptibility weighted imaging (SWI) and gradient recalled echo-T2* (GRE-T2*). MATERIALS AND METHODS: Neuroimaging data gathered from a prospective cohort of CAA patients with probable or definite CAA were retrospectively analyzed by two independent raters. SWI and GRE-T2* were used to assess presence and severity (absent, focal [≤3 sulci] or disseminated [>3 sulci]) of cSS and number of foci. Ratings were compared between sequences and inter-rater agreement was determined. Post hoc analysis explored differences in cSS multifocality scores. RESULTS: We detected cSS in 38 patients with SWI and in 36 with GRE-T2* (70.4% versus 66.7%; P=0.5). The two raters agreed in detecting more disseminated cSS when using SWI: 16 focal (29.63%) and 20 disseminated (37.04%) cases of cSS seen on GRE-T2* and 11 (20.37%) focal and 27 (50%) disseminated cSS cases seen using SWI (P=0.008). Inter-rater agreement was equivalent for the two sequences (κpresence 0.7 versus 0.69; κseverity 0.74 versus 0.66) for assessing both presence and severity of cSS. Post hoc analysis showed higher multifocality scores from both raters' SWI evaluations, with agreement equivalent to that for T2* evaluations. CONCLUSIONS: Our findings suggest that SWI ratings could show more disseminated cSS and higher multifocality scores in advanced CAA patients with inter-rater reliability equivalent to that obtained using GRE-T2*, regardless of level of experience.

Combined trastuzumab and radiation therapy for HER2-positive uterine serous carcinoma: A case report.

Overexpression of HER2 in endometrial cancer is associated with poor prognosis, aggressive disease, and resistance to standard therapies. Recent studies have shown that HER2-targeted therapies, such as trastuzumab, can be effective in treating HER2-positive endometrial cancer in combination with chemotherapy. Currently, the management of advanced-stage HER2-positive uterine serous carcinoma (USC) consists of adjuvant platinum-based chemotherapy with concurrent trastuzumab followed by trastuzumab maintenance therapy until disease recurrence or prohibitive toxicity. In the setting of persistent pelvic disease following systemic therapy, consolidation with tumor-directed radiation therapy also offers an opportunity to eradicate residual disease. With the emergence of molecular tumor classifications and systemic therapies (chemotherapy, immunotherapy, and target therapies), the landscape of adjuvant multi-modality therapy is ever changing and increasingly individualized. Currently, there is no prospective evidence to guide pelvic radiotherapy with concurrent trastuzumab in endometrial cancer, and as a result, no reported toxicity in endometrial cancer patients. In this case report, we present two patients with HER2-positive USC who received multi-agent chemotherapy with trastuzumab followed by pelvic radiation therapy and concurrent trastuzumab. Both patients tolerated this multimodal treatment without significant or persistent moderate or severe adverse events. These two cases provide insight into the safety and feasibility of administering radiation therapy with trastuzumab in endometrial cancer in the maintenance phase. Our report suggests that trastuzumab-based therapy may be a promising treatment option for HER2-positive endometrial cancer patients who receive concurrent or adjuvant chemotherapy and radiation therapy.

Increasing global accessibility to high-level treatments for cervical cancers.

Human papillomaviruses (HPV)-related gynecological cancers are a major health care issue, and a leading cause of cancer death in low- and middle-income countries (LMIC). In 2020, the World Health Organization launched a program aimed at cervical cancer elimination, by screening and vaccination strategies. Offering the best possible care to women diagnosed with invasive cancer is a complementary objective. Treatment of cervical cancer as per modern standards is complex and multimodal, mainly relying on surgery, external-beam radiotherapy (+/-chemotherapy) and brachytherapy. In parallel with the pivotal role of multidisciplinary discussion, international societies provide guidance to define the most effective and least toxic anti-cancer strategy, homogenize treatment protocols and provide benchmark quality indicators as a basis for accreditation processes. The challenge is to offer the appropriate diagnostic workup and treatment upfront and to avoid non- evidence-based treatment that consumes resources, impairs quality of life (QoL), and compromises oncological outcome. Various strategies may be applied for improving treatment quality: development of surgical mentorship, companion-training programs and international cooperation. The lack of radiotherapy/brachytherapy facilities is a major concern in LMIC. Reinforcing international support in terms of education, training, research and development and technical cooperation with national projects is required to increase access to minimum requirements but also introduce modern techniques, upgrade radiotherapy/brachytherapy services, and expand access to modern systemic treatments. In countries with robust economies, compliance to standards should also be increased. Integrative cancer care and multidisciplinary approaches are needed to tackle the dual challenge of increasing cure rates while minimizing QoL impairment. Appropriate dimensioning of the resources to avoid harmful treatment delays and access to expert referral centers is also a priority.

Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Whole-brain network connectivity has been shown to be a useful biomarker of cerebral amyloid angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in cerebral amyloid angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS: We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable cerebral amyloid angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to cerebral amyloid angiopathy (non-cerebral amyloid angiopathy-mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with cerebral amyloid angiopathy-mild cognitive impairment and non-cerebral amyloid angiopathy-mild cognitive impairment and explored its associations with cognitive functions and conventional markers of cerebral small-vessel disease, using linear regression models. RESULTS: Subjects with Cerebral amyloid angiopathy-mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-cerebral amyloid angiopathy-mild cognitive impairment (P < .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with cerebral amyloid angiopathy, after adjusting for other MRI markers of cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-cerebral amyloid angiopathy-mild cognitive impairment. CONCLUSIONS: Peak width of skeletonized mean diffusivity is altered in cerebral amyloid angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in cerebral amyloid angiopathy and could be a useful biomarker for cognition in this population.

CTA Protocols in a Telestroke Network Improve Efficiency for Both Spoke and Hub Hospitals.

BACKGROUND AND PURPOSE: Telestroke networks support screening for patients with emergent large-vessel occlusions who are eligible for endovascular thrombectomy. Ideal triage processes within telestroke networks remain uncertain. We characterize the impact of implementing a routine spoke hospital CTA protocol in our integrated telestroke network on transfer and thrombectomy patterns. MATERIALS AND METHODS: A protocol-driven CTA process was introduced at 22 spoke hospitals in November 2017. We retrospectively identified prospectively collected patients who presented to a spoke hospital with National Institutes of Health Stroke Scale scores ≥6 between March 1, 2016 and March 1, 2017 (pre-CTA), and March 1, 2018 and March 1, 2019 (post-CTA). We describe the demographics, CTA utilization, spoke hospital retention rates, emergent large-vessel occlusion identification, and rates of endovascular thrombectomy. RESULTS: There were 167 patients pre-CTA and 207 post-CTA. The rate of CTA at spoke hospitals increased from 15% to 70% (P < .001). Despite increased endovascular thrombectomy screening in the extended window, the overall rates of transfer out of spoke hospitals remained similar (56% versus 54%; P = .83). There was a nonsignificant increase in transfers to our hub hospital for endovascular thrombectomy (26% versus 35%; P = .12), but patients transferred >4.5 hours from last known well increased nearly 5-fold (7% versus 34%; P < .001). The rate of endovascular thrombectomy performed on patients transferred for possible endovascular thrombectomy more than doubled (22% versus 47%; P = .011). CONCLUSIONS: Implementation of CTA at spoke hospitals in our telestroke network was feasible and improved the efficiency of stroke triage. Rates of patients retained at spoke hospitals remained stable despite higher numbers of patients screened. Emergent large-vessel occlusion confirmation at the spoke hospital lead to a more than 2-fold increase in thrombectomy rates among transferred patients at the hub.

Paediatric dental A&E service during the COVID-19 pandemic in the Greater London area.

PURPOSE: The UK government introduced a nationwide lockdown on the 23rd March 2020 to prevent the spread of COVID-19. All elective hospital and dental practice assessments and procedures were mandated to stop. Key hospital dental workers were required to work, and Guy's and St Thomas' NHS Foundation Trust became a designated Urgent Dental Care Centre (UDC) for the greater London area. The paediatric dental emergency walk-in service was suspended and replaced with a telephone triage system and evaluation of digital images sent by parents/carers when needed. The aim of this paper is to describe the emergency service provided by staff in the department of Paediatric Dentistry at St Thomas' Hospital during the first lockdown. METHODS: A prospective service evaluation of the modified paediatric dental emergency service was carried out between 25th March and 29th May 2020. RESULTS: Four-hundred and sixty-four patients accessed the paediatric dental emergency service via telephone during the service evaluation period. Of these, 192 (41%) had dental pain, 121 (26%) had pain and swelling of dental origin, and 89 (19%) had trauma. CONCLUSIONS: Remote telephone consultations and digital photographs were useful to screen emergency paediatric dental patients, but lack of face-to-face consultations with radiographic assessment and access to general anaesthetic services were major limiting factors.

Surgineering: curriculum concept for experiential learning in upper-level biomedical engineering.

PURPOSE: A strong foundation in the fundamental principles of medical intervention combined with genuine exposure to real clinical systems and procedures will improve engineering students' capability for informed innovation on clinical problems. To help build such a foundation, a new course (dubbed Surgineering) was developed to convey fundamental principles of surgery, interventional radiology (IR), and radiation therapy, with an emphasis on experiential learning, hands-on with real clinical systems, exposure to clinicians, and visits to real operating theaters. The concept, structure, and outcomes of the course of the first run of the first semester of the course are described. METHOD: The course included six segments spanning fundamental concepts and cutting-edge approaches in a spectrum of surgical specialties, body and neurological IR, and radiation therapy. Each class involved a minimum of didactic content and an emphasis on hands-on experience with instrumentation, equipment, surgical approaches, anatomical models, dissection, and visits to clinical theaters. Outcomes on the quality of the course and areas for continuing improvement were assessed by student surveys (5-point Likert scores and word-cloud representations of free response) as well as feedback from clinical collaborators. RESULT: Surveys assessed four key areas of feedback on the course and were analyzed quantitatively and in word-cloud representations of: (1) best aspects (hands-on experience with surgeons); (2) worst aspects (quizzes and reading materials); (3) areas for improvement (projects, quizzes, and background on anatomy); and (4) what prospective students should know (a lot background reading for every class). Five-point Likert scores from survey respondents (16/19 students) indicated: overall quality of the course 4.63 ± 0.72 (median 5.00); instructor teaching effectiveness 4.06 ± 1.06 (median 4.00); intellectual challenge 4.19 ± 0.40 (median 4.00); and workload somewhat heavier (62.5%) compared to other courses. Novel elements of the course included the opportunity to engage with clinical faculty and participate in realistic laboratory exercises, work with clinical instruments and equipment, and visit real operating theaters. An additional measure of the success of the course was evidenced by surveys and a strong escalation in enrollment in the following year. CONCLUSIONS: The Surgineering course presents an important addition to upper-level engineering curricula and a valuable opportunity for engineering students to gain hands-on experience and interaction with clinical experts. Close partnership with clinical faculty was essential to the schedule and logistics of the course as well as to the continuity of concepts delivered over the semester. The knowledge and experience gained provides stronger foundation for identification of un-met clinical needs and ideation of new engineering approaches in medicine. The course also provides a valuable prerequisite to higher-level coursework in systems engineering, human factors, and data science applied to medicine.

Genome Mining-Based Identification of Identical Multirepeat Sequences in Plasmodium falciparum Genome for Highly Sensitive Real-Time Quantitative PCR Assay and Its Application in Malaria Diagnosis.

Developing ultrasensitive methods capable of detecting submicroscopic parasitemia-a challenge that persists in low transmission areas, asymptomatic carriers, and patients showing recrudescence-is vital to achieving malaria eradication. Nucleic acid amplification techniques offer improved analytical sensitivity but are limited by the number of copies of the amplification targets. Herein, we perform a novel genome mining approach to identify a pair of identical multirepeat sequences (IMRSs) that constitute 170 and 123 copies in the Plasmodium falciparum genome and explore their potential as primers for PCR. Real-time quantitative PCR analyses have shown the ability of P. falciparum IMRSs to amplify as low as 2.54 fg of P. falciparum genomic DNA (approximately 0.1 parasite), with a striking 100-fold increase in detection limit when compared with P. falciparum 18S rRNA (251.4 fg; approximately 10 parasites). Validation with clinical samples from malaria-endemic regions has shown 6.70 ± 1.66 cycle better detection threshold in terms of Ct value for P. falciparum IMRSs, with approximately 100% sensitivity and specificity. Plasmodium falciparum IMRS assays are also capable of detecting submicroscopic infections in asymptomatic samples. To summarize, this approach of initiating amplification at multiple loci across the genome and generating more products with increased analytical sensitivity is different from classic approaches amplifying multicopy genes or tandem repeats. This can serve as a platform technology to develop advanced diagnostics for various pathogens.

Global Collaborations for Cervical Cancer: Can the East-West Alliance Facilitate Treatment for all?

Despite the advances in the primary prevention of cervical cancer, there is an absolute increase in the incidence of cervical cancer as a result of an increase in world population. A vast majority of patients in low and low-middle income countries continue to present at a locally advanced stage, necessitating treatment with chemoradiation and brachytherapy. There is a dearth of equipment and trained professionals for the treatment of cervical cancer, especially in low and low-middle income countries. There is an urgent need to improve treatment availability and develop better treatments. Worldwide trends, however, reveal a low number of therapeutic and innovative research trials in cervical cancer. The present article elucidates the existing challenges and provides solutions to improve outcomes. The proposed strategies hinge on strengthening collaborations for global advocacy.

Early transplantation into a vesicostomy: a safe approach for managing patients with severe obstructive lesions who are not candidates for bladder augmentation.

INTRODUCTION: Management of severe antenatally detected oligohydramnios with and without obstruction is improving with the result that more fetuses are surviving with early renal failure. Significant advances have occurred in all specialties involved in the management of these patients. All these specialties working together have resulted in the survival of more patients born with renal failure. OBJECTIVE: The aim of this study is to highlight the medical advances in antenatal management of fetal oligohydramnios and pulmonary hypoplasia and to demonstrate that transplantation into a diverted urinary system is safe and leads to good outcomes. STUDY DESIGN: A case series of five patients were presented who, at the study center's respective facilities, recently underwent renal transplantation into bladders drained by cutaneous vesicostomy after extensive bladder evaluation and whose clinical cases highlight the aim of this study. RESULTS: A total of 5 patients were reviewed. Renal failure was caused by posterior urethral valves in four patients, and in one patient Eagle-Barrett syndrome. One patient received an amnio-infusion and attempted antenatal bladder shunt. One patient was ventilator dependent until 24 months, and required a tracheostomy, while two patients were ventilator dependent for the first few months of life. Three of five patients were dialysis dependent. Patient age at transplantation ranged from 20 to 61 months. All patients were poorly compliant pre-transplant and had bladder capacities ranging from 10 mL to 72 mL. Months since follow-up ranged from 3 to 64 months. Creatinine levels prior to transplant ranged from 1.9 to 5.6. During the follow up period, this range decreased to 0.13 to 0.53. Two of five patients had UTI episodes since transplantation. Patient A showed Banff Type 1A acute T-cell mediated rejected approximately two months after transplant, but subsequent biopsies have been negative for rejection. Patient A also required a vesicostomy revision approximately two months after transplant and balloon dilation of UVJ anastomosis three months after transplant. DISCUSSION: Vesicostomy is an especially attractive option to manage children with small bladders to accommodate the high urinary output that occurs after transplantation in infants who require an adult kidney. Recent advances in antenatal management such as amnioinfusion for oligohydramnios have made significant impacts in pulmonary and renal management of this patient population over recent years. CONCLUSION: This report provides further support for the use of vesicostomy as an option for surgical management of patients with renal failure with oligohydramnios and severe obstructive lesions identified antenatally. It also indicates the need to update the criteria for antenatal management of oligohydramnios in obstructive and anephric patients.

Insights on Heme Synthesis in the Malaria Parasite.

The malaria parasite has a functional heme-biosynthetic pathway, although it can access host hemoglobin-heme. The heme pathway is dispensable for blood stages, but essential in the mosquito stages which do not acquire hemoglobin-heme. We propose that the blood stage parasites maintain a dynamic heme pool through multiple back-up mechanisms.

Postoperative MRI Evaluation of a Radiofrequency Cordotomy Lesion for Intractable Cancer Pain.

BACKGROUND AND PURPOSE: There are limited data on the use of postoperative imaging to evaluate the cordotomy lesion. We aimed to describe the cordotomy lesion by using postoperative MR imaging in patients after percutaneous cordotomy for intractable cancer pain. MATERIALS AND METHODS: Postoperative MR imaging and clinical outcomes were prospectively obtained for 10 patients after percutaneous cordotomy for intractable cancer pain. Area, signal intensity, and location of the lesion were recorded. Clinical outcomes were measured by using the Visual Analog Scale and the Brief Pain Inventory-Short Form, and correlations with MR imaging metrics were evaluated. RESULTS: Ten patients (5 men, 5 women; mean age, 58.5 ± 9.6 years) were included in this study. The cordotomy lesion was hyperintense with central hypointense foci on T2-weighted MR imaging, and it was centered in the anterolateral quadrant at the C1-C2 level. The mean percentage of total cord area lesioned was 24.9% ± 7.9%, and most lesions were centered in the dorsolateral region of the anterolateral quadrant (66% of the anterolateral quadrant). The number of pial penetrations correlated with the percentage of total cord area that was lesioned (r = 0.78; 95% CI, 0.44-0.89; P = .008) and the length of T2-weighted hyperintensity (r = 0.85; 95% CI, 0.54-0.89; P = .002). No significant correlations were found between early clinical outcomes and quantitative MR imaging metrics. CONCLUSIONS: We describe qualitative and quantitative characteristics of a cordotomy lesion on early postoperative MR imaging. The size and length of the lesion on MR imaging correlate with the number of pial penetrations. Larger studies are needed to further investigate the clinical correlates of MR imaging metrics after percutaneous cordotomy.

Effect of CTA Tube Current on Spot Sign Detection and Accuracy for Prediction of Intracerebral Hemorrhage Expansion.

BACKGROUND AND PURPOSE: Reduction of CT tube current is an effective strategy to minimize radiation load. However, tube current is also a major determinant of image quality. We investigated the impact of CTA tube current on spot sign detection and diagnostic performance for intracerebral hemorrhage expansion. MATERIALS AND METHODS: We retrospectively analyzed a prospectively collected cohort of consecutive patients with primary intracerebral hemorrhage from January 2001 to April 2015 who underwent CTA. The study population was divided into 2 groups according to the median CTA tube current level: low current (<350 mA) and high current (≥350 mA). CTA first-pass readings for spot sign presence were independently analyzed by 2 readers. Baseline and follow-up hematoma volumes were assessed by semiautomated computer-assisted volumetric analysis. Sensitivity, specificity, positive and negative predictive values, and accuracy of spot sign in predicting hematoma expansion were calculated. RESULTS: This study included 709 patients (288 and 421 in the low- and high-current groups, respectively). A higher proportion of low-current scans identified at least 1 spot sign (20.8% versus 14.7%, P = .034), but hematoma expansion frequency was similar in the 2 groups (18.4% versus 16.2%, P = .434). Sensitivity and positive and negative predictive values were not significantly different between the 2 groups. Conversely, high-current scans showed superior specificity (91% versus 84%, P = .015) and overall accuracy (84% versus 77%, P = .038). CONCLUSIONS: CTA obtained at high levels of tube current showed better diagnostic accuracy for prediction of hematoma expansion by using spot sign. These findings may have implications for future studies using the CTA spot sign to predict hematoma expansion for clinical trials.

Influence of medical student career aims on ophthalmic surgical simulator performance (part of the international forum for ophthalmic simulation studies).

BACKGROUND: To evaluate whether medical students who have expressed a strong desire to pursue ophthalmology as a career perform simulated ophthalmic surgical tasks to a higher level than medical students whose interests lie elsewhere. METHODS: All participants were fourth or fifth year students at University College London (UCL) Medical School, London, UK. One cohort was recruited from the Moorfields Academy, an ophthalmic forum designed to enhance collaboration and innovation within the specialty. These students were therefore seen as highly motivated, expressing a desire to pursue a career in ophthalmology. The other cohort of students was invited to participate during their fourth year UCL Ophthalmology attachment, but expressed interest in non-ophthalmic disciplines. Participants carried out a single attempt of three modules on the Eyesi Surgical Simulator, and total and mean scores were calculated out of 100. RESULTS: 13 academy and 15 non-academy students were enrolled. The overall mean scores were 51/100 for the academy group, range 0-97, and 45.5/100 for the non-academy group, range 0-90 (p=0.49). Scores for precision testing, forceps training and capsulorrhexis training for academy versus non-academy were 45.8 versus 37.8 (p=0.61), 57.1 versus 52.3 (p=0.8) and 50.2 versus 46.4 (p=0.55), respectively. CONCLUSIONS: This study is the first to suggest that medical students with a strong career interest in ophthalmology do not perform microsurgical tasks to a higher level than medical students who have no goal in this area. This also indicates variation in scores between novices, which may serve as a pitfall in the use of simulators as a tool for entry into training.

Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections.

The proteins of Plasmodium, the malaria parasite, are strikingly rich in asparagine. Plasmodium depends primarily on host haemoglobin degradation for amino acids and has a rudimentary pathway for amino acid biosynthesis, but retains a gene encoding asparagine synthetase (AS). Here we show that deletion of AS in Plasmodium berghei (Pb) delays the asexual- and liver-stage development with substantial reduction in the formation of ookinetes, oocysts and sporozoites in mosquitoes. In the absence of asparagine synthesis, extracellular asparagine supports suboptimal survival of PbAS knockout (KO) parasites. Depletion of blood asparagine levels by treating PbASKO-infected mice with asparaginase completely prevents the development of liver stages, exflagellation of male gametocytes and the subsequent formation of sexual stages. In vivo supplementation of asparagine in mice restores the exflagellation of PbASKO parasites. Thus, the parasite life cycle has an absolute requirement for asparagine, which we propose could be targeted to prevent malaria transmission and liver infections.

Decoupling of structural and functional brain connectivity in older adults with white matter hyperintensities.

Age-related impairments in the default network (DN) have been related to disruptions in connecting white matter tracts. We hypothesized that the local correlation between DN structural and functional connectivity is negatively affected in the presence of global white matter injury. In 125 clinically normal older adults, we tested whether the relationship between structural connectivity (via diffusion imaging tractography) and functional connectivity (via resting-state functional MRI) of the posterior cingulate cortex (PCC) and medial prefrontal frontal cortex (MPFC) of the DN was altered in the presence of white matter hyperintensities (WMH). A significant correlation was observed between microstructural properties of the cingulum bundle and MPFC-PCC functional connectivity in individuals with low WMH load, but not with high WMH load. No correlation was observed between PCC-MPFC functional connectivity and microstructure of the inferior longitudinal fasciculus, a tract not passing through the PCC or MPFC. Decoupling of connectivity, measured as the absolute difference between structural and functional connectivity, in the high WMH group was related to poorer executive functioning and memory performance. These results suggest that such decoupling may reflect reorganization of functional networks in response to global white matter pathology and may provide an early marker of clinically relevant network alterations.

Warfarin-related intraventricular hemorrhage: imaging and outcome.

OBJECTIVE: Oral anticoagulation therapy (OAT) with warfarin increases mortality and disability after intracerebral hemorrhage (ICH), the result of increased ICH volume and risk of hematoma expansion. We investigated whether OAT also influences risk of development of intraventricular hemorrhage (IVH), the volume of IVH and IVH expansion, and whether IVH is a substantive mediator of the overall effect of OAT on ICH outcome. METHODS: We performed a retrospective analysis of a prospectively collected single-center cohort of 1,879 consecutive ICH cases (796 lobar, 865 deep, 153 cerebellar, 15 multiple location, 50 primary IVH) from 1999 to 2009. ICH and IVH volumes at presentation, as well as hematoma expansion (>33% or >6 mL increase) and IVH expansion (>2 mL increase), were determined using established semiautomated methods. Outcome was assessed at 90 days using either the modified Rankin Scale or Glasgow Outcome Scale. RESULTS: Warfarin use was associated with IVH risk, IVH volume at presentation, and IVH expansion in both lobar and deep ICH (all p < 0.05) in a dose-response relationship with international normalized ratio. Warfarin was associated with poor outcome in both lobar and deep ICH (p < 0.01), and >95% of this effect was accounted for by baseline ICH and IVH volumes, as well as ICH and IVH expansion. CONCLUSION: Warfarin increases IVH volume and risk of IVH expansion in lobar and deep ICH. These findings (along with effects on ICH volume and expansion) likely represent the mechanisms by which anticoagulation worsens ICH functional outcome.

Statin use and outcome after intracerebral hemorrhage: case-control study and meta-analysis.

OBJECTIVES: Intracerebral hemorrhage (ICH) is a highly lethal disease of the elderly. Use of statins is increasingly widespread among the elderly, and therefore common in patients who develop ICH. Accumulating data suggests that statins have neuroprotective effects, but their association with ICH outcome has been inconsistent. We therefore performed a meta-analysis of all available evidence, including unpublished data from our own institution, to determine whether statin exposure is protective for patients who develop ICH. METHODS: In our prospectively ascertained cohort, we compared 90-day functional outcome in 238 pre-ICH statin cases and 461 statin-free ICH cases. We then meta-analyzed results from our cohort along with previously published studies using a random effects model, for a total of 698 ICH statin cases and 1,823 non-statin-exposed subjects. RESULTS: Data from our center demonstrated an association between statin use before ICH and increased probability of favorable outcome (odds ratio [OR] = 2.08, 95% confidence interval [CI] 1.37-3.17) and reduced mortality (OR = 0.47, 95% CI 0.32-0.70) at 90 days. No compound-specific statin effect was identified. Meta-analysis of all published evidence confirmed the effect of statin use on good outcome (OR = 1.91, 95% CI 1.38-2.65) and mortality (OR = 0.55, 95% CI 0.42-0.72) after ICH. CONCLUSION: Antecedent use of statins prior to ICH is associated with favorable outcome and reduced mortality after ICH. This phenomenon appears to be a class effect of statins. Further studies are required to clarify the biological mechanisms underlying these observations.