Fatal Intracranial Hemorrhage Research Articles

Rivaroxaban at Non-Valvular Atrial Fibrillation: a Prospective Study and Clinical Practice

The article presents an analytical review of the results of post-registration clinical studies on the efficacy and safety of rivaroxaban in nonvalvular atrial fibrillation (AF) to prevent stroke and other systemic thromboembolic complications. The main purpose of the first large prospective international observational study of rivaroxaban for stroke prevention in patients with non-valvular AF patients XANTUS was the analysis of efficacy and safety of rivaroxaban in clinical practice. Results of one year of observation of 6784 patients confirmed that rivaroxaban is effective and safe in real unselected population of patients with non-valvular AF and various stroke risk. The first Russian multicenter observational study Neuro-Xar dedicated to secondary prevention of stroke and systemic embolism, demonstrated the efficacy and safety of rivaroxaban in routine clinical practice. Lower risk of fatal intracranial and gastrointestinal bleeding was found in retrospective post-marketing studies, of rivaroxaban in the US, such as the PMSS and REVISIT-US. Rivaroxaban therapy was associated with reduced risk of the combined endpoint (ischemic stroke and intracranial hemorrhage).

Atherothrombotic Risk Stratification and the Efficacy and Safety of Vorapaxar in Patients With Stable Ischemic Heart Disease and Previous Myocardial Infarction.

Patients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar. We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2.5 years (median) in TRA 2°P-TIMI 50 [Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50]. The efficacy and safety of vorapaxar (SCH 530348; MK-5348) were assessed by baseline risk among patients with previous MI without prior stroke or transient ischemic attack for whom there is a clinical indication for vorapaxar. End points were cardiovascular death, MI, or ischemic stroke and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding. The 9 independent risk predictors were age, diabetes mellitus, hypertension, smoking, peripheral arterial disease, previous stroke, previous coronary bypass grafting, heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of cardiovascular death/MI/ischemic stroke and the individual components (P for trend <0.001 for all). High-risk patients (≥3 risk indicators; 20% of population) had a 3.2% absolute risk reduction in cardiovascular disease/MI/ischemic stroke with vorapaxar, and intermediate-risk patients (1-2 risk indicators; 61%) had a 2.1% absolute risk reduction (P<0.001 each), translating to a number needed to treat of 31 and 48. Bleeding increased across risk groups (P for trend<0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients. Stratification of baseline atherothrombotic risk can assist with therapeutic decision making for vorapaxar use for secondary prevention after MI. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00526474.

Fatal Intracranial Haemorrhage due to HPA-2b Incompatible Foetal Alloimmune Thrombocytopenia and Antenatal Management of Subsequent Pregnancy

Intracranial hemorrhage as a presenting feature of neonatal Alloimmune thrombocytopenia is an uncommon manifestation and is a predictor of recurrent risk in future pregnancy. The index child had an uncommon Human Platelet Antigen (HPA-2b) causing feto-maternal incompatibility leading to in-utero intracranial hemorrhage. The rarity of this antigen in the population posed a challenge in establishing the diagnosis. With the aid of HPA genotyping the father was found to be heterozygous for this antigen which led to proceed with the antenatal diagnosis of the condition in the subsequent pregnancy. Keywords: Neonatal Alloimmune Thrombocytopenia, NAIT, Human Platelet Antigen, Antenatal Diagnosis, Intracranial Hemorrhage

Update on Anticoagulation: What the Interventional Radiologist Needs to Know.

The novel oral anticoagulants (NOACs) represent a major advance in the treatment of patients with nonvalvular atrial fibrillation and venous thromboembolism (VTE). They have several advantages over vitamin-K antagonists such as warfarin, including more predictable pharmacokinetics and improved safety, particularly with fatal bleeding and intracranial hemorrhage. However, several issues remain surrounding the use of NOACs in certain subpopulations and with the approach to reversal. The periprocedural management of anticoagulation with these relatively new agents can also present several challenges. This article reviews the basic pharmacology, efficacy, and safety of these drugs. Several populations at higher risk for complications with use of NOACs are discussed, including those undergoing procedures. Finally, several target-specific reversal agents have either received FDA approval or likely will be approved in the near future; these agents and their roles in the approach to anticoagulation reversal will also be discussed.

Feasibility and efficacy of thrombolysis in acute ischemic stroke: A study from National Institute of Neurological and Allied Sciences, Kathmandu, Nepal.

Background:Stroke is the major cause of morbidity and mortality worldwide. The number of stroke patients receiving recombinant tissue plasminogen activator (rt-PA), also known as Alteplase, in the developing world is extremely low. We aim to study the feasibility and efficacy of thrombolysis for the 1st time in our country.Materials and Methods:In this retrospective study (July 2012-August 2015), acute ischemic stroke patients who were thrombolyzed within 3 h of stroke onset were included. Their demographic profiles, clinical profiles, risk factors, type of thrombolytic used, and outcomes were systematically recorded and analyzed.Results:A total of 9 patients were thrombolyzed. The mean time from the onset of stroke symptoms to first dose of rt-PA (onset to treatment) was 1.2 h. Six patients had good neurological outcome as measured by modified Rankin Scale (mRS). The median mRS at discharge was 3. Thrombolysis-related post treatment complication was noted in 44.4%, of which nonfatal intracranial bleed occurred only in 2 patients (22.2%). None of the patients receiving intravenous tenecteplase had thrombolysis-related complications, and none of the patients had fatal intracranial bleed.Conclusion:This study clearly demonstrates the beginning of a feasible and effective thrombolysis in the treatment of acute ischemic stroke in Nepal.

Fatal Intracranial Hemorrhage in a Patient with Disseminated Intravascular Coagulation associated with Sepsis

Fatal Intracranial Hemorrhage in a Patient with Disseminated Intravascular Coagulation associated with Sepsis

Effective Management of Acute Promyelocytic Leukemia with High Risk of Fatal Intracranial Hemorrhage

Although the prognosis of acute promyelocytic leukemia (APL) are favorable because of disease-specific drugs, such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), early death due to fatal intracranial hemorrhage has been observed in many cases. The aim of this study is to examine the relationship between the treatment and intracranial hemorrhage complication in APL patients.46 patients diagnosed of APL during a period from 2000 to 2014 in our hospital were examined. The distribution of fatal intracranial hemorrhage (FICH) risk score in the 46 APL patients showed 23.9%, 58.6% and 17.3% for low, intermediate, and high categories, respectively. Among the 46 patients, 5 patients developed intracranial hemorrhage before remission, including 4 patients who developed such hemorrhage after chemotherapy and ATRA administration, and 1 patient who developed intracranial hemorrhage before treatment. All of the 5 patients were included in the high risk group of FICH score, including 1 patient who died and 3 patients who had serious paralysis. These hemorrhage tended to expand for several days because of progression of disseminated intravascular coagulation (DIC) accompanied by tumor lysis syndrome after chemotherapy. Based on this experience, we firstly provided single administration of ATRA for 5 days to a patient with intracranial hemorrhage and then added chemotherapy after improvement of DIC. As a result, we could lead remission with no expansion of intracranial hemorrhage. In most of induction therapy protocols for APL, patients with high white blood cell counts are recommended to receive combination of chemotherapy and ATRA with a focus on ATRA syndrome, but the risk of fatal intracranial hemorrhage is not reflected in the treatment regimen. Such a complication may be prevented using initial single administration of ATRA followed by concomitant chemotherapy after treatment for DIC in patients with a high-risk FICH score.

Improving Patient Outcomes in Preventing Atrial Fibrillation-related Stroke with Non-Vitamin K Antagonist Oral Anticoagulants

The rising incidence of atrial fibrillation (AF) is increasingly resulting in a substantial worldwide increase in AF-related stroke, particularly in elderly patients and this is creating an increasingly serious healthcare burden. Guidelines recommend the use of AF-related stroke prophylaxis but adherence to these remains poor. Studies conducted in the 1990s showed that warfarin reduced the risk of AF-related stroke by an overall 64% compared with placebo. Subsequently, prophylactic treatment was further improved with the development of non-vitamin K antagonist oral anticoagulants (NOACs). More recently, a meta-analysis of four large clinical trials on NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) showed there was a relative risk reduction of 0.81 (p&lt;0.0001) favouring NOAC treatment over warfarin for stroke or systemic embolic events in patients with AF. The largest trial of NOACs in AF-related stroke, to date, was the ENGAGE AF-TIMI 48 study (n=21,105) which showed that edoxaban was non-inferior to warfarin for ischaemic stroke reduction but significantly reduced bleeding and cardiovascular mortality. A recent subgroup analysis of this study showed that with edoxaban the incidences of intracranial haemorrhage (ICH) subtypes (all ICH, fatal ICH, fatal, subdural and epidural bleed) were significantly lower with 60 mg of edoxaban (p=0.013–&lt;0.001). Edoxaban was also shown to be an effective option in patients with prior stroke. In addition, edoxaban was shown to reduce deaths due to fatal bleeds compared with warfarin. The results of current studies, especially the ENGAGE AF-TIMI 48 subgroup analysis therefore, show that the benefits of anticoagulation therapy in patients with AF substantially outweigh the risks.

Effectiveness and Safety of Rivaroxaban in Treatment of Venous Thromboembolism in Cancer Patients

IntroductionPatients with active cancer have a high risk for venous thromboembolism (VTE). The current treatment of choice for cancer-associated thrombosis is low molecular weight heparin (LMWH). Evidence for the efficacy and safety of the target-specific oral anticoagulants in the prevention and treatment of cancer-associated thrombosis is limited. In the EINSTEIN trials, comparing rivaroxaban to LMWH plus a vitamin K antagonist, only a small number of patients with active cancer received treatment with rivaroxaban (6.8% [n=118] in EINSTEIN-DVT1 and 4.7% [n=114] in EINSTEIN-PE2). The use of rivaroxaban over LMWH for cancer-associated thrombosis is not recommended by the current guidelines.3 However, due to the parenteral route of administration and high cost burden of LMWH, some cancer patients at our institution have received rivaroxaban for cancer-associated thrombosis.MethodAn observational chart review was performed to determine the effectiveness and safety of rivaroxaban for the treatment of VTE in cancer patients by observing recurrent VTE and bleeding events. For the effectiveness endpoint, patients who received rivaroxaban for less than one month were excluded from the study. For the safety analysis, patients who received at least one dose of rivaroxaban were included in the study.ResultA total of 92 cancer patients with VTE who received rivaroxaban at Huntsman Cancer Institute were selected for the study. Median age was 60 years old and 54% (n=50) were male. Average estimated creatinine clearance at the initiation of rivaroxaban was 96.2 mL/min (range 31.8-241 mL/min, Cockcroft-Gault). Thirty-eight patients (41%) were treated for DVT (deep venous thromboses), 32 patients (35%) had PE (pulmonary embolism), and 19 patients (21%) had both DVT and PE.A total of 20 patients (21.7%) had a bleeding event while on therapy (see table). Ten patients (10.8%) experienced a major bleed and the median time to major bleeding was 4.4 months (IQR 2.4-11.6 months). One patient had a fatal intracranial bleed. Four patients (4.3%) had critical bleeding and 5 patients (5.4%) had a clinically relevant bleeding with ≥ 2g/dL drop in hemoglobin level and/or required ≥2 units of red blood cell transfusion. Pharmacodynamic interactions may have contributed to 3 major bleeds, including one patient on aspirin, another on ibuprofen, and the third patient on both aspirin and clopidogrel at the time of bleeding. Seven patients were taking rivaroxaban 20 mg daily at the time of the major bleed. The median platelet count at the time of bleeding was 170k/µL (IQR 108-333k/µL). One patient had a platelet count of 17 k/µL and was admitted with sepsis at the time of bleed. Ten patients (10.8%) experienced minor symptomatic bleeds and the median time to bleeding was 2.5 months (IQR 0.73-4.8 months).Only 4 patients (4.3%) experienced recurrent VTE while on rivaroxaban. Two patients had recurrent DVT. Two patients developed recurrent PE and both were admitted to the hospital for parenteral anticoagulation. The median time to recurrent VTE was 5.7 months (IQR 2.5-11 months). The median platelet count at the time of recurrence was 120 k/µL (range 26-216k/µL). One patient had a known thrombophilia, Factor V Leiden mutation.ConclusionThese data suggest that rivaroxaban may be a safe and acceptable alternative to LMWH for the treatment and secondary prevention of cancer-associated thrombosis. Table 1Huntsman Cancer Institute (n=92)EINSTEIN-DVT1(Cancer sub-group, n=118)EINSTEIN-PE2(Cancer sub-group, n=114)CLOT trial4(n=336)Major bleeding10.8% (n=10)14.4% (n=17)12.3% (n=14)14% (n=47)Clinically relevant non-major bleeding10.8% (n=10)Recurrent DVT2.2% (n=2)3.4% (n=4)n/a4.2% (n=14)Recurrent PE2.2% (n=2)n/a1.8% (n=2)3.9% (n=13)

A Single-Center Retrospective Analysis of a Pediatric Salvage Chemotherapy Regimen for Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia

Background: Relapsed or refractory acute lymphoblastic leukemia (ALL) remains challenging to treat with an extremely poor prognosis. Salvage chemotherapy regimens can achieve complete remission (CR) rates of 30-50%, but CRs are not durable without hematopoietic stem cell transplant (HSCT). Outcomes in untreated adolescents and young adults have improved with the use of pediatric chemotherapy regimens, but data on the use of pediatric chemotherapy regimens in relapsed/refractory adult ALL is lacking. We chose to retrospectively examine the outcomes of adult patients with relapsed ALL at our institution treated with the CCG-1941 pediatric salvage protocol (Gaynon PS, et al. J Clin Oncol 2006).Methods: We conducted a single-center retrospective cohort study of patients aged 18 and older with relapsed/refractory ALL who were treated with the CCG-1941 protocol. Patients received induction with vincristine, dexamethasone, ifosfamide, etoposide, PEG-asparaginase, and methotrexate, as well as intrathecal methotrexate, cytarabine, and hydrocortisone prophylaxis, followed by intensification and continuation phases. This regimen was offered to relapsed/refractory patients who, in the judgement of treating physician, were likely to tolerate multiagent chemotherapy. All adult patients who received this regimen between 2006 and 2015 were included in the analysis. Outcomes of interest were: the CR rate, duration of remission (DOR), toxicity, 30-day mortality, and the rate of patients undergoing HSCT.Results: Between January 2006 and April 2015, 15 patients aged 20-54 (median 31) with first relapse (n=12) or refractory (n=3) ALL were treated with the CCG-1941 regimen. Baseline patient characteristics are described in the Table 1. Seven patients (47%) had alterations to the induction protocol. The majority of these modifications were reduction or omission of PEG-asparaginase or vincristine. All patients experienced infectious complications, most commonly neutropenic fever (n= 12, 80%, 95% CI 52-96). There was one death due to infection, which occurred during an intensification phase. Two patients had grade 3 pancreatitis and two patients had hemorrhage (one grade 2, and one grade 5). 30-day mortality was 7% (95% CI 0-32) due to one fatal intracranial hemorrhage. Median length of hospitalization for induction was 28 days (range 10-61).Twelve patients (80%, 95% CI 52-96) achieved CR, and six of these patients received 1-2 cycles of intensification or continuation. Among the remaining 6 CR patients, one proceeded immediately to HSCT, two received other consolidation, two had early relapse, and one was lost to follow up. Six patients proceeded directly to HSCT, and one more underwent HSCT after receiving subsequent therapies for relapsed disease. The DOR was 81% at 6 months, 54% at 12 months, 36% at 18+ months and 18% at 24 months. One patient has been followed for 63 months and has not recurred. Median follow-up for survivors was 16 months (range 3.6-63).Conclusions: The CCG-1941 regimen appears to be tolerable and efficacious in adult patients with relapsed/refractory ALL. This regimen has been previously reported only in children. Despite the regimen's toxicities, a substantial proportion of patients underwent subsequent stem cell transplantation. Such salvage therapies remain important options for patients with T-ALL and for those B-ALL patients who are not candidates for, or who have failed phenotype-specific immunotherapies. Further prospective, multicenter study is warranted for use of pediatric salvage regimens in the adult patient population. [Display omitted] DisclosuresFoster:Celgene: Research Funding.

Oral Anticoagulant Prescription in Patients With Atrial Fibrillation and a Low Risk of Thromboembolism: Insights From the NCDR PINNACLE Registry.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an estimated 1 in 4 lifetime risk in those older than 40 years of age and a projected increase in prevalence to approximately 5.6 million affected individuals in the United States by the year 2050 (1,2). In patients with AF at higher risk for thromboembolism, anticoagulation with warfarin (a vitamin K antagonist) or the newer novel anticoagulants reduces morbidity and mortality (3–6). Because oral anticoagulant use carries a risk of bleeding, including potentially fatal intracranial hemorrhage, anticoagulant treatment is not recommended in AF patients at a particularly low risk for stroke. Specifically, previous AF guidelines recommend against the use of oral anticoagulation in patients under 60 years of age without heart disease or other known risk factors for thromboembolism (7), and more recently updated guidelines do not recommend oral anticoagulation in AF patients without any established risk factor for stroke (8). Although it is well known that appropriate oral anticoagulant prescription in AF patients at risk for stroke outside clinical trial settings falls short of guideline-based expectations (9–12), it is unknown whether young and healthy AF patients with the lowest stroke risk are being treated with oral anticoagulation that may increase bleeding risk without a commensurate reduction in stroke risk. To our knowledge, a real-world evaluation of guideline adhering practice patterns of anticoagulation prescription in AF patients with the lowest stroke risk has never been performed. We evaluated the prevalence of oral anticoagulant prescription by cardiovascular specialists in a cohort of outpatients using data from the National Cardiovascular Data Registry (NCDR)’s Practice Innovation and Clinical Excellence (PINNACLE) Registry®. Use of this prospective national registry of cardiovascular care in the United States provides a unique opportunity to examine patterns of oral anticoagulant treatment in routine practice among outpatients as well as clinical predictors of this practice.

Childhood casualties during civil war: Syrian experience

In war areas a lot of children die as well as adults. According to UNICEF, almost 2 million children have died in the wars took place in the last 10 years. In this study, we aimed to evaluate demographical data and injury characteristics of Syrian children who were wounded in Syria Civil War and died while being treated in Turkey.Postmortem examination and autopsy reports of 985 forensic deaths from Hatay -a Syrian neighborhood city of Turkey-between January 2012 and August 2014 were analyzed retrospectively. Among 763 Syrian people who were wounded in the war and died while being treated in Turkey, 140 cases (18.3%) who were younger than 18 years of age were taken into the scope of this study.Among those cases 77.9% (n = 109) were male and 22.1% were female. Median ages of female cases are 14 (min–max: 2–18) and median age of female cases are 9 (min–max: 1–18). Frequency distribution is highest between 13 and 18 years of age (n: 71, 50.7%). In 70% (n: 98) of cases, cause of death is bombing and shrapnel injuries, 13.6% (19) of them were killed by gunshot wounds. According to injury sites most of the injuries were reported to be on multiple body parts (54.3%, n: 76) and only head and neck injuries (%30). Cause of death was intracranial bleeding and cerebral parenchymal injury in most of the cases (n: 66, %47.1) followed by vascular damage with external bleeding (n: 15, %10.7) and internal organ damage with internal bleeding (n: 15, %10.7). The cases had very high level Abbreviated Injury Scales and Injury Severity Sores.In conclusion, a lot of children have died in the Civil War of Syria. Their average abbreviated injury scale and injury severity score values reported very high. Children that we evaluated were mostly died of head and neck injuries predominantly caused by bombing attacks and Autopsies of them revealed fatal intracranial hemorrhages and parenchymal injuries.

To test or not to test … decision analysis of decision support.

To test or not to test … decision analysis of decision support.

Early Experience With Automatic Pressure-Controlled Cerebrospinal Fluid Drainage During Thoracic Endovascular Aortic Repair

Purpose: To report initial experience with automatic pressure-controlled cerebrospinal fluid drainage (CSFD) during thoracic endovascular aortic repair (TEVAR). Methods: A prospective nonrandomized study enrolled 30 consecutive patients (median age 68 years, range 42–89; 18 men) who underwent TEVAR between March 2012 and July 2013 and were considered to be at high risk for postoperative spinal cord ischemia (SCI), fulfilling 2 of the following criteria: stent-graft length >20 cm, left subclavian artery coverage, and previous infrarenal aortic repair. All patients received perioperative CSFD via the LiquoGuard system. The protocol aimed for a CSF pressure of 10 mm Hg and duration of CSFD of 3 or 7 days in asymptomatic or symptomatic patients, respectively. Muscle strength of the lower extremities was assessed with the Oxford muscle strength grading scale. Results: Completion of the CSFD protocol was achieved in 26 (87%) of 30 patients. CSFD was prematurely stopped due to catheter dislocation in 1 patient and bloody spinal fluid in 3 patients. CSFD was performed for a median of 3 days (range 1–7). Median total CSFD volume was 714 mL (range 13–2369), with a median 192 mL drained per 24 hours. The SCI rate was 3% (1/30). CSFD-related complications were observed in 33% of the patients: 1 fatal intracranial hemorrhage, 3 bloody spinal fluid episodes, 3 persistent CSF leaks requiring epidural blood patch, and 3 post lumbar puncture headaches. Mortality during a median follow-up of 16 months (range 10–25) was 3% (1/30). Conclusion: Prophylactic CSFD was associated with a low SCI rate in a high-risk patient collective undergoing TEVAR. Monitoring and drainage by an automatic modus was feasible, reproducible, and reliable but associated with relevant drainage-associated complications.

Leptomeningeal collateral vessels are a major risk factor for intracranial hemorrhage after carotid stenting in patients with carotid atherosclerotic plaque

AimTo evaluate the relationship between leptomeningeal collaterals and intracranial hemorrhage (ICH) after carotid artery stenting (CAS).MethodsA retrospective study was undertaken of 228 patients (median age 75 years (range 44–90); 187...

Recurrent cerebral/cerebellar infarcts and hemorrhages in a patient with oral anticoagulants for prosthetic valve

Patients on long-term oral anticoagulant therapy (OAT) for prosthetic valves require close monitoring of their international normalized ratio (INR) levels to prevent deleterious effects. We present a case of a 35-year-old male with a known case of rheumatic heart disease who underwent mitral valve replacement and aortic valve replacement. In our patient, there was an undulation of coagulation parameters between low (INR-2.1) and high (INR-6.0) target levels, which eventually lead to ischemic strokes and fatal intracranial hemorrhage (ICH). Repeat INR was 6.0, which was much beyond the therapeutic range. Attempts to correct the coagulation abnormalities did not succeed and the patient succumbed to ICHs. All patients with valve replacement require chronic OAT. Judicious monitoring of the INR levels with dose adjustments can reduce morbidity and mortality from OAT-related complications like hemorrhage and infarction.

P1-10-2 - Three Cases of Fatal Intracranial Hemorrhage with Metastasis of Gastric Cancer to the Bone/Bone Marrow

We present three cases of intracranial hemorrhage with metastasis of gastric cancer to the bone/bone marrow. Case1: A 62-year-old man with history of distal gastrectomy 15 years ago was pointed out to have elevated ALP level and diffuse increased uptake of bone scintigraphy, which turned out to be a recurrence of diffuse metastases to bone and bone marrow confirmed by bone marrow biopsy. After partially successful treatment of chemotherapy with 6 cycles of TS-1 + CDDP, he developed an acute subdural hematoma, complicated by DIC. Craniotomy for removal of hematoma was performed. However, he was died of brain bleeding 12 months after diagnosis of recurrence. Case2: A 60-year-old man underwent subtotal gastrectomy 9 years ago. Similarly, diffuse bone and bone marrow metastasis was confirmed by bone marrow biopsy with trigger of elevated ALP level and diffuse increased uptake of bone scintigraphy. After chemotherapy with TS-1 + CDDP as 1st line and DTX as 2nd line was performed, he also developed and died of subdural hematoma with DIC 22months after diagnosis of recurrence. Case3: A 65-year-old woman with rheumatoid arthritis was pointed out to have low platelet and elevation of LDH and ALP in her regular visits. Endoscope examinations and imaging studies showed gastric cancer with multiple metastases to bone and bone marrow complicated by DIC. Although chemotherapy with TS-1 and blood transfusion was performed, she developed an acute subdural hematoma and received craniotomy for removal of hematoma. However she died of brain rebleeding 4 months after initial diagnosis.The following things are quite interesting in these 3 cases. 1) The former 2cases recurred with bone and bone marrow metastasis after long interval. 2) All cases developed bone and bone marrow metastasis complicated by fatal intracranial hemorrhage without obvious bleeding tendencies in other parts of body. We will discuss those issues with literature review.

Hypoparathyroidism, Hypothyroidism and Thrombocytopenia: Rare Constellation of Fahr’s Syndrome

Fahr’s syndrome is a rare progressive unremitting neurological disorder, characterized by abnormal bilaterally symmetric brain calcifications. It is associated with various endocrinopathies such as hypothyroidism, hypoparathyroidism and hypocalcemia. This case opens up a new horizon of thought process, as it illustrates the clinical presentation of Fahr’s syndrome with thrombocytopenia never reported before. It especially emphasizes on the diagnostic significance of combination of thrombocytopenia with seizures in Fahr’s, as this coupling can result in fatal intracranial hemorrhage if timely seizure management is not initiated. J Endocrinol Metab. 2014;4(4):110-111 doi: http://dx.doi.org/10.14740/jem228w

Therapeutic Hypothermia (Different Depths, Durations, and Rewarming Speeds) for Acute Ischemic Stroke: A Meta-analysis

Whether therapeutic hypothermia benefits patients with acute ischemic stroke (AIS) remains controversial. The aim of this study was to evaluate the efficacy and safety of the different depths, durations, and rewarming speeds of therapeutic hypothermia for AIS. The MEDLINE (OVID), EMBASE, and Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) of therapeutic hypothermia for AIS from the inception of the databases to October 2013. After data extraction and quality assessment, a meta-analysis was performed using RevMan 5.1. A total of 6 RCTs involving 252 AIS patients were eligible for the meta-analysis. Subanalyses stratified by depth, duration, and rewarming speed of therapeutic hypothermia were also performed. Our results showed that therapeutic hypothermia was associated with an increased risk of pneumonia (risk ratio = 3.30, 95% CI 1.48-7.34; P = .003, P for heterogeneity = .91, I(2)= 0%). No significant difference was observed between the 2 groups in terms of neurologic outcomes, mortality, and other complications including symptomatic or fatal intracranial hemorrhage, deep vein thrombosis, and atrial fibrillation. These limited data suggest that therapeutic hypothermia does not significantly improve stroke outcomes and may lead to higher rates of pneumonia. Multicenter RCTs with larger samples are needed to confirm the current findings.

Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials

SummaryBackgroundAlteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase.MethodsWe did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3–6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality.FindingsAlteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35–2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05–1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95–1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3%] of 3365, OR 5·55, 95% CI 4·01–7·70, p<0·0001; SITS-MOST definition 124 [3·7%] vs 19 [0·6%], OR 6·67, 95% CI 4·11–10·84, p<0·0001) and of fatal intracranial haemorrhage within 7 days (91 [2·7%] vs 13 [0·4%]; OR 7·14, 95% CI 3·98–12·79, p<0·0001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17·9%) in the alteplase group versus 556 (16·5%) in the control group (hazard ratio 1·11, 95% CI 0·99–1·25, p=0·07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 3–6 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3·0 h and about 5% for patients treated after 3·0 h, up to 4·5 h.InterpretationIrrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 4·5 h of stroke onset, with earlier treatment associated with bigger proportional benefits.FundingUK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.