Natural Course of Cerebral Cavernous Malformations in Children: A Five-Year Follow-Up Study

Background and Purpose: The purpose of this study was to investigate the natural course of cerebral cavernous malformations (CCM) in the pediatric population, with special emphasis on the risk of first and recurrent bleeding over a 5-year period. Methods: Our institutional database was screened for patients with CCM treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging data set, clinical baseline characteristics, and ≥1 follow-up examination were included. Surgically treated individuals were censored after CCM removal. We assessed the impact of various parameters on first or recurrent intracerebral hemorrhage (ICH) at diagnosis using univariate and multivariate logistic regression adjusted for age and sex. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for (re)hemorrhage. Results: One hundred twenty-nine pediatric patients with CCM were analyzed. Univariate logistic regression identified brain stem CCM (odds ratio, 3.15 [95% CI, 1.15−8.63], P =0.026) and familial history of CCM (odds ratio, 2.47 [95% CI, 1.04−5.86], P= 0.041) as statistically significant predictors of ICH at diagnosis. Multivariate logistic regression confirmed this correlation (odds ratio, 3.62 [95% CI, 1.18−8.99], P= 0.022 and odds ratio, 2.53 [95% CI, 1.07−5.98], P =0.035, respectively). Cox regression analysis identified ICH as mode of presentation (hazard ratio, 14.01 [95% CI, 1.80−110.39], P= 0.012) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of (re)bleeding was 15.9% (95% CI, 10.2%−23.6%) for the entire cohort, 30.2% (20.2%−42.3%) for pediatric patients with ICH at diagnosis, and 29.5% (95% CI, 13.9%−51.1%) for children with brain stem CCM. Conclusions: Pediatric patients with brain stem CCM and familial history of CCM have a higher risk of ICH as mode of presentation. During untreated 5-year follow-up, they revealed a similar risk of (re)hemorrhage compared to adult patients. The probability of (re)bleeding increases over time, especially in cases with ICH at presentation or brain stem localization.

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Modifiable Cardiovascular Risk Factors in Patients With Sporadic Cerebral Cavernous Malformations

Stroke ◽

10.1161/strokeaha.120.031569 ◽

2021 ◽

Author(s):

Bixia Chen ◽

Dino Saban ◽

Steffen Rauscher ◽

Annika Herten ◽

Laurèl Rauschenbach ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Cardiovascular Risk ◽

Arterial Hypertension ◽

Odds Ratio ◽

Cox Regression ◽

Cerebral Cavernous Malformations ◽

Cavernous Malformations ◽

Nicotine Abuse ◽

Mode Of Presentation

Background and Purpose: This study aims to assess the influence of modifiable cardiovascular risk factors on hemorrhage risk of sporadic cerebral cavernous malformations (CCMs). Methods: From 1219 consecutive CCM patients (2003–2018), adult subjects with sporadic CCM and complete magnetic resonance imaging were included. We evaluated presence of intracerebral hemorrhage (ICH) as mode of presentation, occurrence of ICH during follow-up and risk factors arterial hypertension, diabetes, hyperlipidemia, nicotine abuse, and obesity (body mass index >30 kg/m 2 ). Impact of risk factors on ICH at presentation was calculated using univariate and multivariate logistic regression with age and sex adjustment. We performed Kaplan-Meier and Cox regression to analyze cumulative 5-year risk for (re)bleeding. Results: We included 682 patients with CCM. The univariate logistic regression showed a significant relationship (odds ratio=1.938 [95% CI, 1.120–3.353], P =0.018) between obesity and ICH as mode of presentation. Multivariate adjusted logistic regression confirmed significant correlation with odds ratio=1.902 (95% CI, 1.024–3.532, P =0.042). Cox regression did not identify predictors for occurrence of (re)hemorrhage ( P >0.05; hazard ratios: arterial hypertension 1.112 [95% CI, 0.622–1.990], diabetes 0.850 [95% CI, 0.208–3.482], hyperlipidemia 0.719 [95% CI, 0.261–1.981], nicotine abuse 1.123 [95% CI, 0.591–2.134], and obesity 0.928 [95% CI, 0.416–2.070]). Conclusions: This study provides evidence that obesity may be a risk factor for CCM hemorrhage. It was significantly associated with ICH as mode of presentation. Other risk factors (arterial hypertension, diabetes, hyperlipidemia, and current nicotine abuse) showed no such effect. None of the factors showed to be independent predictors for cumulative 5-year risk of (re)bleeding.

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Hemorrhage from cerebral cavernous malformations

Neurology ◽

10.1212/wnl.0000000000009730 ◽

2020 ◽

Vol 95 (1) ◽

pp. e89-e96 ◽

Cited By ~ 1

Author(s):

Bixia Chen ◽

Annika Herten ◽

Dino Saban ◽

Steffen Rauscher ◽

Alexander Radbruch ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Cox Regression ◽

Binary Logistic Regression Analysis ◽

Cerebral Cavernous Malformations ◽

Cavernous Malformations ◽

Cox Regression Analysis ◽

Mode Of Presentation ◽

The Impact

ObjectiveTo determine the role of associated developmental venous anomalies (DVAs) in intracranial hemorrhage (ICH) caused by cerebral cavernous malformations (CCMs).MethodsWe analyzed patient registry data of 1,219 patients with cavernous malformations treated in our institution between 2003 and 2018. Patients with spinal and familial CCM and patients without complete MRI data were excluded. The impact of various variables on ICH as a mode of presentation was assessed with multivariate binary logistic regression analysis. Kaplan Meier/Cox regression analysis was performed to analyze cumulative 5-year-risk for (re)hemorrhage and to identify baseline predictors of this outcome.ResultsSeven hundred thirty-one patients with CCM were included. Multivariate logistic regression confirmed a statistically significant negative correlation with DVA (odds ratio [OR] 0.635 [95% confidence interval (CI) 0.459–0.878]) and positive correlation with brainstem localization (OR 6.277 [95% CI 4.287–9.191]) with ICH as the mode of presentation. Among 731 patients, 76 experienced (re)hemorrhage during 2,338 person-years of follow-up. Overall cumulative 5-year risk was 24.1% (95% CI 21.1%–27.5%). Cox regression analysis revealed initial presentation with ICH (hazard ratio [HR] 8.0 [95% CI 3.549–18.122]) and brainstem localization (HR 2.9 [95% CI 1.756–4.765]) as independent baseline predictors of (re)hemorrhage. Presence of DVA added no independent prognostic information (HR 1.1 [95% CI 0.717–1.885]).ConclusionPatients with CCM with associated DVA are at lower risk to present with ICH. During untreated 5-year follow-up, they showed equal (re)hemorrhage risk compared to patients with CCM without DVA.

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Risk Factors of Changes in Hepatitis B Antibody Status after Allogeneic Hematopoietic Stem Cell Transplantation in Chinese Children with Thalassemia Major

Blood ◽

10.1182/blood.v124.21.5809.5809 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5809-5809

Author(s):

Xiaoqin Feng ◽

Lina Long ◽

Chunfu Li

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Odds Ratio ◽

Thalassemia Major ◽

Enzyme Linked Immunosorbent Assay ◽

Hbv Reactivation ◽

Type I ◽

Multivariate Logistic Regression ◽

Post Transplant

Abstract Objective: This retrospective study evaluated the risk factors involved in the changes in HBsAb status in patients with thalassemia major at a single center in China. Methods: A total of 104 children who underwent allo-HSCT, using NF-08-TM transplant protocol in our center, between January 2010 and June 2012 were recruited.Hepatitis B markers, including HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were examined by TRFIA (time-resolved fluoroimmunoassay) or ELISA (Enzyme-Linked Immunosorbent Assay) for recipients before and after allo-HSCT (at least up to 6 months) and for donors prior to transplantation. HBsAg positive recipients and donors received lamivudine antiviral therapy before allo-HSCT and the treatment was continued in recipients up to 6 months post transplantation. The demographic and clinical characteristics of the patients and their donors were summarized by descriptive statistics. For identification of risk factors that influenced the post-transplant anti-HBs loss and HBV reactivation, both univariate and multivariate logistic regression was used, and odds ratio (OR) and 95% confidence interval (CI) were determined for the covariates that were shown to be statistically significant. All tests were 2-sided, with the type I error rate fixed at 0.05. Statistical analyses were performed using IBM SPSS 20 (SPSS Statistics V20, IBM Corporation, Somers, New York). Results: Of the 104 patients, 2（1.9%） recipients were positive for HBsAg and 102（98.1%） recipients were negative for HBsAg. Of the 102 patients negative for HBsAg before transplantation, the proportion of positive anti-HBs was 69.6% (71 of 102 patients). Of the 104 donors, 99 (95.2%)were negative for HBsAg and 5 (4.8%)were positive for HBsAg. Of the 99 donors negative for HBsAg before transplantation, 72 donors (72.7%) had anti-HBs. After transplantation, of the 69 patients, 27 (39.1%) patients lost their HBV immunity in a median follow-up period of 30 months (range: 21–45); the remaining 42 (60.9 %) patients maintained the immunity against HBV after a median follow-up period of 28.5 months (range: 19–46). 33 patients were anti-HBs negative before the allo-HSCT. The 33 patients included 11 patients with donors who had no anti-HBs and 22 patients with donors who had anti-HBs. After the allo-HSCT, 15 of the 33 patients were found to have newly gained HBV immunity, as represented by the presence of anti-HBs. While 14 of them who developed adoptive immunity had immunized donors (63.6%; 14 out of 22), 1 of them (9.1%; 1 out of 11) with a non-immunized donor (donors without anti-HBs) also had developed HBV immunity. Multivariate logistic regression analysis of 104 patients who underwent allo-HSCT revealed that, patients with pre-HSCT titer of HBsAb < 257.47mIU/mL (adjusted odds ratio, 10.5, 95% CI, 2.1–53.3) and HBsAb-immunized donors (51.3, 2.8–938.6) were significant risk factors for post allo-HSCT HBV loss and acquisition, respectively. In addition, the post-transplant HBV reactivation rate was 11.1%. Conclusions: Current results indicate that pre-transplant HBsAb titer is a key determinant in the loss of HBV immunity after allo-HSCT and HBsAb negative patients with immunized donors are more likely to gain HBV immunity after allo-HSCT than those with non-immunized donors. Further, preemptive antiviral treatment with lamivudine significantly reduces HBV reactivation. This is the first study to have indicated the significant predictors of changes in HBsAg status in children with thalassemia major. Disclosures No relevant conflicts of interest to declare.

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TCF21 variant is a risk factor for coronary artery disease and will it be a prognostic marker?

European Heart Journal ◽

10.1093/ehjci/ehaa946.2904 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Temtem ◽

M Serrao ◽

A Pereira ◽

M Santos ◽

F Mendonca ◽

...

Keyword(s):

Coronary Artery Disease ◽

Logistic Regression ◽

Coronary Artery ◽

Cox Regression ◽

Multivariate Logistic Regression Analysis ◽

Rank Test ◽

Major Adverse Cardiovascular Events ◽

Multivariate Logistic Regression ◽

Artery Disease

Abstract Background TCF21 gene, encodes a basic-helix- loop- helix transcription factor, playing a critical action in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Recent data suggest that TCF21 may play a role in the state of differentiation of SMC precursor cells that migrate to vascular lesions and contribute to fibrous cap. Purpose Investigate the association of TCF21 rs12190287G>C variant with coronary artery disease (CAD) in a Portuguese population and its role on the prognosis. Methods Case-control study with 3120 participants, 1687 coronary patients with at least 75% obstruction of a major coronary artery and 1433 controls. Genotyping used the TaqMan technique (Applied Biosystems) and then a univariate and multivariate logistic regression analysis were performed. After a mean follow-up of 5.01±4.2 years (interquartile range 1.96–7.57), the occurrence of the combined Major Adverse Cardiovascular Events (MACE) (Cardiovascular Mortality, non-fatal Myocardial Infarction, new Revascularization, Cerebrovascular Disease and Peripheric Vascular Disease) were registered and analysed by Cox regression. Finally, Kaplan-Meier survival estimate was performed. Results In the total population, GC+CC genotype was found to be associated with CAD with an OR of 1.285; CI: 1.022–1.614; p=0.031. After multivariate logistic regression, adjusted to traditional risk factors, the association with CAD remained significant for this genotype (OR=1.340; CI: 1.042–1.723; p=0.022).After Cox regression adjusted for confounding variables (age and sex, hypertension, diabetes, smoking, dyslipidemia, eGFR, Ejection fraction <55) the mutated genotype remained a significant predictor of MACE (HR=1.420; CI: 1.032–1.953; p=0.031). The individuals carrying the mutated allele (GC+CC) at the mean follow-up showed an event probability of 36.1%, whereas the wild population (GG) presented only 23.4%. The Log-Rank test showed significant differences between the two curves (p=0.019). Conclusion The mutated TCF21 variant can provide a new marker to identify patients at high cardiovascular risk and may representa potential target for gene therapy in future. Figure 1 Funding Acknowledgement Type of funding source: None

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Natural history of brainstem cavernous malformations: prospective hemorrhage rate and adverse factors in a consecutive prospective cohort

Journal of Neurosurgery ◽

10.3171/2019.12.jns192856 ◽

2020 ◽

pp. 1-12

Author(s):

Da Li ◽

Ze-Yu Wu ◽

Pan-Pan Liu ◽

Jun-Peng Ma ◽

Xu-Lei Huo ◽

...

Keyword(s):

Risk Factor ◽

Natural History ◽

Neurological Deficit ◽

Cox Regression ◽

Developmental Venous Anomaly ◽

Focal Neurological Deficit ◽

Cavernous Malformations ◽

Cox Regression Analysis ◽

History Of

OBJECTIVEGiven the paucity of data on the natural history of brainstem cavernous malformations (CMs), the authors aimed to evaluate the annual hemorrhage rate and hemorrhagic risk of brainstem CMs.METHODSNine hundred seventy-nine patients diagnosed with brainstem CMs were referred to Beijing Tiantan Hospital from 2006 to 2015; 224 patients were excluded according to exclusion criteria, and 47 patients were lost to follow-up. Thus, this prospective observational cohort included 708 cases (324 females). All patients were registered, clinical data were recorded, and follow-up was completed.RESULTSSix hundred ninety (97.5%) of the 708 patients had a prior hemorrhage, 514 (72.6%) had hemorrhagic presentation, and developmental venous anomaly (DVA) was observed in 241 cases (34.0%). Two hundred thirty-seven prospective hemorrhages occurred in 175 patients (24.7%) during 3400.2 total patient-years, yielding a prospective annual hemorrhage rate of 7.0% (95% CI 6.2%–7.9%), which decreased to 4.7% after the 1st year. Multivariate Cox regression analysis after adjusting for sex and age identified hemorrhagic presentation (HR 1.574, p = 0.022), DVA (HR 1.678, p = 0.001), mRS score ≥ 2 on admission (HR 1.379, p = 0.044), lesion size > 1.5 cm (HR 1.458, p = 0.026), crossing the axial midpoint (HR 1.446, p = 0.029), and superficially seated location (HR 1.307, p = 0.025) as independent adverse factors for prospective hemorrhage, but history of prior hemorrhage was not significant. The annual hemorrhage rates were 8.3% and 4.3% in patients with and without hemorrhagic presentation, respectively; the rate was 9.9%, 6.0%, and 1.0% in patients with ≥ 2, only 1, and 0 prior hemorrhages, respectively; and the rate was 9.2% in patients with both hemorrhagic presentation and focal neurological deficit on admission.CONCLUSIONSThe study reported an annual hemorrhage rate of 7.0% exclusively for brainstem CMs, which significantly increased if patients presented with both hemorrhagic presentation and focal neurological deficit (9.2%), or any other risk factor. Patients with a risk factor for hemorrhage needed close follow-up regardless of the number of prior hemorrhages. It should be noted that the referral bias in this study could have overestimated the annual hemorrhage rate. This study improved the understanding of the natural history of brainstem CMs, and the results are important for helping patients and physicians choose a suitable treatment option based on the risk factors and stratified annual rates.Clinical trial registration no.: ChiCTR-POC-17011575 (http://www.chictr.org.cn/).

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Abstract TMP116: Intracranial Hemorrhage Rate in Familial Cerebral Cavernous Malformation Patients

Stroke ◽

10.1161/str.51.suppl_1.tmp116 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Atif Zafar ◽

Jeffrey Nelson ◽

Charles E McCulloch ◽

Joseph Zabramski ◽

Amy L Akers ◽

...

Keyword(s):

Intracranial Hemorrhage ◽

Cox Regression ◽

Prior History ◽

Cavernous Malformations ◽

Cox Regression Analysis ◽

Dominant Disease ◽

History Of ◽

Familial Cerebral Cavernous Malformation ◽

Event Rates

Background: Familial cerebral cavernous malformations (FCCM) is an autosomal dominant disease caused by mutations in three genes: CCM1 , CCM2 , or CCM3 . FCCM patients typically present with multiple brain CCMs that can increase in number and size over time, and can cause intracranial hemorrhage (ICH) and other disabling symptoms, e.g., seizures, headaches, and deficits. Rates and predictors of ICH events in FCCM are not well described. The purpose of this study was to estimate ICH event rates and predictors in a cohort of FCCM patients followed prospectively. Methods: We collected baseline and follow-up data in 316 FCCM patients enrolled from 4 sites in the Brain Vascular Malformation Consortium CCM Project, including age, sex, race, CCM gene, CCM symptoms, and CCM burden (total and large CCMs>5mm) at baseline. We initially recruited CCM1 patients with the Common Hispanic Mutation (CHM), and later expanded to include other genetic types. We performed Kaplan-Meier survival analysis to estimate ICH event rates after enrollment, censoring at date of first treatment, death or last follow-up, out to 10 years. Cox regression analysis was performed to estimate hazard ratios (HR) of predictors, adjusting for age, sex, and family. Results: The majority of patients were female (63%) and of Hispanic ethnicity (83%). CCM gene mutation was known for 82%; 98% had CCM1 mutations (94% with CHM), 1% CCM2 , and 1% CCM3 . At enrollment, mean age was 39±20 years (range: 1-85), 32% had a history of ICH event, 38% had seizures, and 60% had headaches. Mean number of total and large CCMs was 55±103 and 4±7, respectively. Mean follow-up was 4.1±2.7 years. During 1285 person-years (PY) of follow-up, there were 31 ICH events for a rate of 2.4 per 100 PY (95% CI: 1.7-3.4) overall, 4.0 (2.5-6.6) in prior ICH patients, and 1.6 (1.0-2.8) in patients without prior ICH (HR=2.4, 95% CI: 1.2-4.9). ICH-free survival was not statistically significantly different by sex (HR=1.2, 95% CI: 0.6-2.8), age (HR=1.0 per decade, 0.8-1.2), total lesions (HR=1.2 per doubling, 0.9-1.5), or large lesions (HR=1.3 per doubling, 1.0-1.7). Conclusions: FCCM patients with prior history of ICH events are at higher risk for re-hemorrhage during follow-up. Additional studies are needed to identify predictors of ICH risk in FCCM.

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LONG-TERM OUTCOME OF PATIENTS WITH MULTIPLE CEREBRAL CAVERNOUS MALFORMATIONS

Neurosurgery ◽

10.1227/01.neu.0000346269.59554.db ◽

2009 ◽

Vol 65 (3) ◽

pp. 450-455 ◽

Cited By ~ 27

Author(s):

Juri Kivelev ◽

Mika Niemelä ◽

Riku Kivisaari ◽

Reza Dashti ◽

Aki Laakso ◽

...

Keyword(s):

Family History ◽

De Novo ◽

Good Condition ◽

Neurological Deficits ◽

Cerebral Cavernous Malformations ◽

Cavernous Malformations ◽

Long Term Outcome ◽

History Of ◽

The Mean

Abstract OBJECTIVE Multiple cerebral cavernous malformations (MCCMs) typically occur in patients with a family history of these lesions. Literature on MCCMs is scarce, and little is known about their natural history. METHODS Of 264 consecutive patients with cerebral cavernomas treated at the Department of Neurosurgery, Helsinki University Central Hospital, in the past 27 years, 33 patients had MCCMs. Lesions were categorized according to the Zabramski classification scale. Follow-up questionnaires were sent to all patients. Outcome was assessed using the Glasgow Outcome Scale, and amelioration of epilepsy was assessed using the Engel scale. All clinical data were analyzed retrospectively. RESULTS The mean age of patients at diagnosis was 44 years. Sex presentation was almost equal. Nine percent of all patients had a family history of the disease. Patients presented with epilepsy, acute headache, and focal neurological deficits. MCCMs were incidental findings in 2 patients. Altogether, 416 cavernomas were found: 70% supratentorial and 30% infratentorial. Fifteen patients had symptomatic hemorrhage before admission to our department. Surgery was performed on 18 patients. In most cases, the largest cavernoma was removed. Postoperatively, 1 patient experienced temporary hemiparesis, and another developed permanent motor dysphasia. No mortalities occurred. The mean follow-up time was 7.7 years. Twenty-six patients (79%) were in good condition. Among patients with epilepsy who underwent lesionectomy, 70% had an Engel class I outcome. On follow-up magnetic resonance imaging, 52 de novo cavernomas were found. CONCLUSION Surgical treatment of patients with MCCMs is safe. An extirpation of the clinically active cavernoma prevents further bleedings and improves outcome of epilepsy.

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Predictors of hospital mortality among patients with COVID-19 in Tehran, Iran

SAGE Open Medicine ◽

10.1177/20503121211051573 ◽

2021 ◽

Vol 9 ◽

pp. 205031212110515

Author(s):

Fatemeh Esfahanian ◽

SeyedAhmad SeyedAlinaghi ◽

Nazanin Janfaza ◽

Marcarious M. Tantuoyir

Keyword(s):

Logistic Regression ◽

Confidence Interval ◽

Odds Ratio ◽

Adjusted Odds Ratio ◽

Laboratory Data ◽

Hospitalized Patients ◽

Multivariate Logistic Regression ◽

Predictors Of Mortality ◽

Laboratory Test Results ◽

History Of

Objective: The coronavirus disease 2019 (COVID-19) has become a global pandemic. Timely and effective predictors of survival and death rates are crucial for improving the management of COVID-19 patients. In this study, we evaluated the predictors of mortality based on the demographics, comorbidities, clinical characteristics, laboratory findings, and vital signs of 500 patients with COVID-19 admitted at Imam Khomeini Hospital Complex, the biggest hospital in Tehran, Iran. Methods: Five hundred hospitalized laboratory-confirmed COVID-19 patients were included in this study. Subsequently, electronic medical records, including patient demographics, clinical manifestation, comorbidities, and laboratory test results were collected and analyzed. They were divided into two groups: expired and discharged. Demographics, clinical, and laboratory data were compared among the two groups. The related factors with death in the patients were determined using univariate and multivariate logistic regression approaches. Results: Among the 500 hospitalized patients, most patients were male (66.4% versus 33.6%). The expired group had more patients ⩾70 years of age compared with the discharged group (32.9% versus 16.3%, respectively). Almost 66% of the expired patients were hospitalized for ⩾5 days which was higher than the discharge group (26.9%). Patients with a history of opium use in the expired group were significantly higher compared to the discharged group (14.8% versus 8.6%, p = 0.04) as well as a history of cancer (15.5% versus 4.7%, p < 0.001). Out of the 500 patients with COVID-19, four patients (2.6%) were HIV positive, all of whom expired. Dyspnea (76.4%), fever (56.6%), myalgia (59.9%), and dry cough (67%) were the most common chief complaints of hospitalized patients. Age ⩾70 years (adjusted odds ratio = 2.49; 95% confidence interval, 1.02–6.04), being female (adjusted odds ratio = 2.06; 95% confidence interval, 1.25–3.41), days of hospitalization (adjusted odds ratio = 5.73; 95% confidence interval, 3.49–9.41), and having cancer (adjusted odds ratio = 3.23; 95% confidence interval, 1.42–7.39) were identified as independent predictors of mortality among COVID-19 patients. Conclusion: Discharged and expired COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principal component analysis. The mortality risk factors for severe patients identified in this study using a multivariate logistic regression model included elderly age (⩾70 years), being female, days of hospitalization, and having cancer.

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Chronic Lateral Ankle Instability

The American Journal of Sports Medicine ◽

10.1177/0363546508319050 ◽

2008 ◽

Vol 36 (11) ◽

pp. 2167-2172 ◽

Cited By ~ 121

Author(s):

Woo Jin Choi ◽

Jin Woo Lee ◽

Seung Hwan Han ◽

Bom Soo Kim ◽

Su Keon Lee

Keyword(s):

Logistic Regression ◽

Confidence Interval ◽

Odds Ratio ◽

Ligament Reconstruction ◽

Ankle Instability ◽

Multivariate Logistic Regression ◽

Lateral Ankle ◽

Chronic Lateral Ankle Instability ◽

Lateral Ankle Instability

Background There has been no attempt to correlate the type and number of intra-articular lesions with the results of ligament reconstruction for chronic lateral ankle instability. Hypothesis Certain intra-articular lesions affect the clinical outcome of ligament reconstruction. Study Design Case series; Level of evidence, 4. Methods Sixty-five ankles from 64 patients underwent a modified Broström operation for chronic lateral ankle instability with a mean follow-up of 28.7 months (range, 12–67). The results were assessed according to the Karlsson-Peterson Ankle Score. The type of intra-articular lesions and the association of clinical outcome were investigated using Pearson's correlation coefficient and multivariate logistic regression analysis. Results The average Karlsson-Peterson Ankle Score was improved from 53 ± 14.63 preoperatively to 85.21 ±11.97 at final follow-up ( P < .001). Five different intra-articular lesions were described in 63 ankles (96.9%), and the ankle score negatively correlated with the number of lesions ( r = −.604; P < .001). Multivariate logistic regression showed that syndesmosis widening (odds ratio, 11.1; 95% confidence interval: 2.2–55.4; P = .003), osteochondral lesions of the talus (odds ratio, 8.5; 95% confidence interval: 1.7–42.3; P = .008), and ossicles (odds ratio, 4.5; 95% confidence interval: 1.0–20.2; P = .046) are significant predictors of unsatisfactory results after ligament reconstruction. Conclusion Arthroscopic diagnosis and treatment of intra-articular lesions associated with chronic lateral ankle instability is a safe and effective method. The presence of any combination of associated intra-articular lesions can result in a poor outcome.

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Association of Annexin A5 Resistance with Silent Infarct in Sickle Cell Disease

Blood ◽

10.1182/blood.v124.21.1394.1394 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1394-1394

Author(s):

Kerry A. Morrone ◽

Xue Xiaonan ◽

Suzette O. Oyeku ◽

Jane A. Little ◽

Catherine Driscoll ◽

...

Keyword(s):

Logistic Regression ◽

Sickle Cell ◽

Odds Ratio ◽

Lupus Anticoagulant ◽

Reticulocyte Count ◽

Outcome Variable ◽

Annexin A5 ◽

Cell Disease ◽

Multivariate Logistic Regression ◽

History Of

Abstract Background: In sickle cell disease (SCD) abnormally shaped RBCs interact with white blood cells and the endothelium, leading to a vasculopathy and thrombotic/ prothrombotic complications such as stroke and pulmonary hypertension. About 10 % of patients with a thrombotic event in the general population will have the presence of an antiphospholipid (aPL) antibody (Andreoli et al. 2013). One proposed mechanism for the thrombophilic nature of aPL antibodies is the disruption of annexin A5. Annexin A5 is a potent anticoagulant protein that has an affinity to phospholipids. In the presence of aPL antibodies, annexin A5 is unable to form its crystallized anticoagulant shield (annexin A5 resistance). There is a paucity of data which assesses the association of aPL antibodies with vasculopathic complications of SCD, and there have been no studies investigating the annexin A5 resistance assay (A5R). We designed a pilot study assessing aPL antibody levels and A5R in a pediatric sickle cell population. Methods: Patients with a history of stroke, abnormal transcranial doppler (TCD) and elevated TR gradient by echocardiography (>25mm of Hg) were eligible. A5R, lupus anticoagulant- DRRVT, anti β2GP1, anti phosphatidylserine and anti cardiolipin antibody (IgG, IgA, IgM) assays were performed on samples obtained prospectively when patients were at a steady state (at least 4 weeks after an acute event). A5R measures coagulation times in the presence and absence of annexin A5. Resistance to the anticoagulant effects of annexin is expressed as a reduction in this ratio (Rand et al. 2004). Statistical analysis assessed multiple variables including age, gender, hemoglobin, reticulocyte count, LDH, hydroxyurea therapy, transfusion therapy, elevated TR gradient, stroke and silent stroke. Univariate analysis and multivariate logistic regression was performed with abnormal annexin A5 as the outcome variable. Results:There were a total of 39 patients: 12 patients with a history of stroke, 6 with an elevated TCD velocity and 15 patients with an elevated TR gradient. Of the 27 patients that did not have a stroke, 25 had a screening MRI in the prior year, and 9 of these patients had silent infarcts. Only 1 of 39 patients had elevated anticardiolipin IgG antibodies and 1 had an abnormal lupus coagulant (DRVVT). In contrast, 5/39 patients (12.8%) had low or abnormal annexin A5 resistance, 7/39 (18%) were in the borderline range and 27/39 (69%) were normal. This frequency of abnormality was unexpected in the antiphospolipid antibody and lupus anticoagulant negative population. None of the patients, except the one with the positive lupus anticoagulant, developed any thrombotic events in 3.5 years of follow up. None of the patients with overt stroke or abnormal TCDs had an abnormal A5R. Multivariate logistic regression analyses showed statistically significant association of hemoglobin (p= 0.037, OR 0.25, CI 0.07-0.92)), age (p =0.047, OR 1.43, CI 1.01-2.04) and silent infarct (p =0.015, OR 28.5, CI 1.9-420.5) with abnormal annexin A5 resistance. A multivariate analysis using linear regression with annexin A5 resistance as a continuous outcome variable (Table 1), showed persistence of the significant association of silent infarcts (p =0.037). Conclusion: We report an association between annexin A5 resistance and low hemoglobin, older age and presence of silent infarct in a subgroup of SCD patients. Prevalence of abnormal aPL antibody assays and lupus anticoagulant was strikingly low in this cohort. A potential role for perturbed annexin A5 resistance in the pathophysiology of silent infarction in SCD will need to be evaluated further in carefully designed prospective studies and may be a novel therapeutic target. Table 1. Hemoglobin, Age and Silent Stroke are Associated with Abnormal Annexin A5 Resistance Characteristic Odds Ratio Odds Ratio Confidence Interval p-value Hemoglobin* 0.25 0.07-0.92 0.037 Reticulocyte count 0.77 0.54-1.08 0.13 LDH 1.00 0.99-1.00 0.51 Age* 1.43 1.01-2.04 0.047 Monocyte count 1.00 1.00-1.00 0.34 Silent infarct* 28.5 1.9-420.5 0.015 Stroke 0.47 0.05-4.88 0.53 Elevated TR gradient 0.34 0.03-3.49 0.36 Gender 0.47 0.05-4.88 0.53 Allosensitization 0.56 0.05-5.86 0.63 HU vs no treatment 0.46 0.03-6.93 0.58 Transfusion vs no treatment 0.18 0.01-4.26 0.29 Disclosures No relevant conflicts of interest to declare.

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