COVID-19’s natural course among ambulatory monitored outpatients

AbstractResearch objective was to detail COVID-19’s natural trajectory in relation to the Czech population’s viral load. Our prospective detailed daily questionnaire-based telemonitoring study evaluated COVID-19’s impact among 105 outpatients. In accordance with government quarantine requirements, outpatients were divided into a cohort with two negative tests at the end of the disease (40 patients) and a cohort with a new algorithm (65 patients) following a 14-day quarantine. Median follow-up differed significantly between the 2 groups (23 days vs. 16 days). Only 6% of patients were asymptomatic during the entire telemonitoring period. Another 13% of patients were diagnosed asymptomatic, as suspected contacts, yet later developed symptoms, while the remaining 81% were diagnosed as symptomatic on average 6 days following symptom onset. Telemonitoring enabled precise symptom status chronicling. The most frequently reported complaints were fevers, respiratory issues, and anosmia. Six patients were eventually hospitalized for complications detected early after routine telemonitoring. During the extended follow-up (median 181 days), anosmia persisted in 26% of patients. 79% of patients in the new quarantine algorithm cohort reported no symptoms on day 11 compared to just 56% of patients in the two negative test cohort upon first testing negative (median–19 days). The highest viral load occurred within 0–2 days of initial symptom onset. Both the PCR viral load and two consecutive PCR negative sample realizations indicated high interindividual variability with a surprisingly fluctuating pattern among 43% of patients. No definitive COVID-19 symptoms or set of symptoms excepting anosmia (59%) and/or ageusia (47%) were identified. No preexisting medical conditions specifically foreshadowed disease trajectory in a given patient. Without a PCR negativity requirement for quarantine cessation, patients could exhibit fewer symptoms. Our study therefore highlights the urgent need for routine ambulatory patient telemedicine monitoring, early complication detection, intensive mass education connecting disease demeanor with subsequent swift diagnostics, and, notably, the need to reevaluate and modify quarantine regulations for better control of SARS-CoV-2 proliferation.

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COVID-19’s Natural Course Among Ambulatory Monitored Outpatients

10.21203/rs.3.rs-148835/v1 ◽

2021 ◽

Author(s):

Barbora Weinbergerova ◽

Jiri Mayer ◽

Stepan Hrabovsky ◽

Zuzana Novakova ◽

Zdenek Pospisil ◽

...

Keyword(s):

Viral Load ◽

Symptom Onset ◽

Interindividual Variability ◽

Initial Symptom ◽

Negative Sample ◽

Ambulatory Patient ◽

Disease Trajectory ◽

High Interindividual Variability ◽

Symptom Status

Abstract Background: Research objective was to detail COVID-19’s natural trajectory in relation to the Czech population’s viral load.Methods: Our prospective detailed daily questionnaire-based telemonitoring study evaluated COVID-19’s impact among 105 outpatients. In accordance with government quarantine requirements, outpatients were divided into a cohort with two negative tests at the end of the disease (40 patients) and a cohort with a new algorithm (65 patients) following a fourteen-day quarantine.Results: Median follow-up differed significantly between the 2 groups (23 days vs. 16 days). Only 6% of patients were asymptomatic during the entire telemonitoring period. 13% of patients were diagnosed asymptomatic, as suspected contacts, yet later developed symptoms, while the remaining 81% were diagnosed on average 6 days following symptom onset. Telemonitoring enabled precise symptom status chronicling. The most frequently reported complaints were fevers, respiratory issues, and anosmia. Six patients were eventually hospitalized for complications detected early after routine telemonitoring. During the extended follow-up (median 181 days), anosmia persisted in 26% of patients. 79% of patients in the new quarantine algorithm cohort reported no symptoms on day 11 compared to just 56% of patients in the two negative test cohort upon first testing negative (median–19 days). The highest viral load occurred within 0-2 days of initial symptom onset. Both the PCR viral load and two consecutive PCR negative sample realizations indicated high interindividual variability with a surprisingly fluctuating pattern among 43% of patients.Conclusions: No definitive COVID-19 symptoms or set of symptoms excepting anosmia (59%) and/or ageusia (47%) were identified. No preexisting medical conditions specifically foreshadowed disease trajectory in a given patient. Without a PCR negativity requirement for quarantine cessation, patients could exhibit fewer symptoms. Our study therefore highlights the urgent need for routine ambulatory patient telemedicine monitoring, early complication detection, intensive mass education connecting disease demeanor with subsequent swift diagnostics, and, notably, the need to reevaluate and modify quarantine regulations for better control of SARS-CoV-2 proliferation.

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A rapid review and meta-analysis of the asymptomatic proportion of PCR-confirmed SARS-CoV-2 infections in community settings

Wellcome Open Research ◽

10.12688/wellcomeopenres.16387.1 ◽

2020 ◽

Vol 5 ◽

pp. 266 ◽

Cited By ~ 1

Author(s):

Sarah Beale ◽

Andrew Hayward ◽

Laura Shallcross ◽

Robert W. Aldridge ◽

Ellen Fragaszy

Keyword(s):

Viral Load ◽

Meta Analysis ◽

Random Effect ◽

Rapid Review ◽

Community Settings ◽

Cross Sectional ◽

Symptom Monitoring ◽

Viral Shedding ◽

Symptom Status

Background: Cross-sectional studies indicate that up to 80% of active SARS-CoV-2 infections may be asymptomatic. However, accurate estimates of the asymptomatic proportion require systematic detection and follow-up to differentiate between truly asymptomatic and pre-symptomatic cases. We conducted a rapid review and meta-analysis of the asymptomatic proportion of PCR-confirmed SARS-CoV-2 infections based on methodologically appropriate studies in community settings. Methods: We searched Medline and EMBASE for peer-reviewed articles, and BioRxiv and MedRxiv for pre-prints published before 25/08/2020. We included studies based in community settings that involved systematic PCR testing on participants and follow-up symptom monitoring regardless of symptom status. We extracted data on study characteristics, frequencies of PCR-confirmed infections by symptom status, and (if available) cycle threshold/genome copy number values and/or duration of viral shedding by symptom status, and age of asymptomatic versus (pre)symptomatic cases. We computed estimates of the asymptomatic proportion and 95% confidence intervals for each study and overall using random effect meta-analysis. Results: We screened 1138 studies and included 21. The pooled asymptomatic proportion of SARS-CoV-2 infections was 23% (95% CI 16%-30%). When stratified by testing context, the asymptomatic proportion ranged from 6% (95% CI 0-17%) for household contacts to 47% (95% CI 21-75%) for non-outbreak point prevalence surveys with follow-up symptom monitoring. Estimates of viral load and duration of viral shedding appeared to be similar for asymptomatic and symptomatic cases based on available data, though detailed reporting of viral load and natural history of viral shedding by symptom status were limited. Evidence into the relationship between age and symptom status was inconclusive. Conclusion: Asymptomatic viral shedding comprises a substantial minority of SARS-CoV-2 infections when estimated using methodologically appropriate studies. Further investigation into variation in the asymptomatic proportion by testing context, the degree and duration of infectiousness for asymptomatic infections, and demographic predictors of symptom status are warranted.

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Prolonged Viral Shedding in Patients with Mild to Moderate COVID-19 Disease: A Regional Perspective

Infectious Diseases Research and Treatment ◽

10.1177/11786337211010428 ◽

2021 ◽

Vol 14 ◽

pp. 117863372110104

Author(s):

Mehrab E Hossain ◽

David Lister ◽

Caroline Bartolo ◽

Paul M Kinsella ◽

James Knox ◽

...

Keyword(s):

Symptom Onset ◽

Initial Symptom ◽

Duration Of Symptoms ◽

Mild Disease ◽

Viral Shedding ◽

Moderate Disease ◽

Increased Risk ◽

Initial Symptoms ◽

Polymerase Chain

Background The risk of transmission of Coronavirus Disease 2019 (COVID-19) is increasingly understood to be greatest early after symptom onset, however, factors associated with prolonged and increased risk of transmission remain unclear. In settings where COVID-19 prevalence is low, there may be a benefit of extending the period that patients are isolated to decrease the risk of transmission. This study explored the duration of viral shedding in such a location, in patients with mild-moderate COVID-19 disease in Ballarat, Australia. Methods Patients diagnosed with COVID-19 disease using a real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay from oropharyngeal and bilateral deep nasopharyngeal sampling and managed through Ballarat Health Services between March 1 and May 1, 2020 were included. Patients were retested if they were afebrile for >72 hours, asymptomatic and >14 days since symptom onset. If positive on retesting, patients were tested every 3 to 7 days thereafter. Results Patients underwent testing a median of 4 days (range 1-12) after initial symptom onset. Duration of symptoms ranged from 1 to 36 days. Positive tests were recorded up to a median of day 21 (range 6-38). Cycle thresholds were inversely correlated with time since symptom onset ( P < .0001). Median time to the first negative test was 25 days (range 12-32). Two patients who had remained asymptomatic for >7 days after initial symptom onset had recrudescence of mild symptoms on day 13 and 14; both tested positive on follow-up tests at this time. Conclusions This study demonstrates prolonged shedding of COVID-19 in patients with mild-moderate disease. It suggests that some patients with mild disease may have recrudescence of symptoms a week or more after their initial symptoms resolved.

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A Rapid Review and Meta-Analysis of the Asymptomatic Proportion of PCR-Confirmed SARS-CoV-2 Infections in Community Settings

10.1101/2020.05.20.20108183 ◽

2020 ◽

Cited By ~ 1

Author(s):

Sarah Beale ◽

Andrew Hayward ◽

Laura Shallcross ◽

Robert W Aldridge ◽

Ellen Fragaszy

Keyword(s):

Viral Load ◽

Meta Analysis ◽

Random Effect ◽

Rapid Review ◽

Community Settings ◽

Cross Sectional ◽

Symptom Monitoring ◽

Viral Shedding ◽

Symptom Status

AbstractBackgroundUp to 80% of active SARS-CoV-2 infections are proposed to be asymptomatic based on cross-sectional studies. However, accurate estimates of the asymptomatic proportion require systematic detection and follow-up to differentiate between truly asymptomatic and pre-symptomatic cases. We conducted a rapid review and meta-analysis of the asymptomatic proportion of PCR-confirmed SARS-CoV-2 infections based on methodologically-appropriate studies in community settings.MethodsWe searched Medline and EMBASE for peer-reviewed articles, and BioRxiv and MedRxiv for pre-prints published before 25/08/2020. We included studies based in community settings that involved systematic PCR testing on participants and follow-up symptom monitoring regardless of symptom status. We extracted data on study characteristics, frequencies of PCR-confirmed infections by symptom status, and (if available) cycle threshold/genome copy number values and/or duration of viral shedding by symptom status, and age of asymptomatic versus (pre)symptomatic cases. We computed estimates of the asymptomatic proportion and 95% confidence intervals for each study and overall using random effect meta-analysis.FindingsWe screened 1138 studies and included 21. The pooled asymptomatic proportion of SARS-CoV-2 infections was 23% (95% CI 16%-30%). When stratified by testing context, the asymptomatic proportion ranged from 6% (95% CI 0-17%) for household contacts to 47% (95% CI 21-75%) for non-outbreak point prevalence surveys with follow-up symptom monitoring. Estimates of viral load and duration of viral shedding appeared to be similar for asymptomatic and symptomatic cases based on available data, though detailed reporting of viral load and natural history of viral shedding by symptom status were limited. Evidence into the relationship between age and symptom status was inconclusive.ConclusionAsymptomatic viral shedding comprises a substantial minority of SARS-CoV-2 infections when estimated using methodologically-appropriate studies. Further investigation into variation in the asymptomatic proportion by testing context, the degree and duration of infectiousness for asymptomatic infections, and demographic predictors of symptom status are warranted.

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Hepatitis B virus (HBV) viral load, liver and renal function in adults treated with tenofovir disoproxil fumarate (TDF) vs. untreated: a retrospective longitudinal UK cohort study

BMC Infectious Diseases ◽

10.1186/s12879-021-06226-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Tingyan Wang ◽

David A. Smith ◽

Cori Campbell ◽

Jolynne Mokaya ◽

Oliver Freeman ◽

...

Keyword(s):

Viral Load ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Renal Impairment ◽

Clinical Guidelines ◽

Untreated Group ◽

Liver Inflammation ◽

B Virus ◽

The Impact

Abstract Background Current clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients. Methods We studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively. Results We included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years, p = 0.004) and more likely to be male (63% vs. 47%, p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group. Conclusions Risk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population.

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797. Management of Patients with Multiple Clostridioides difficile Infection Recurrences using a Tapered-Pulsed Fidaxomicin Strategy

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.987 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S441-S442

Author(s):

Xing Tan ◽

Andrew M Skinner ◽

Benjamin Sirbu ◽

Larry H Danziger ◽

Dale N Gerding ◽

...

Keyword(s):

First Episode ◽

Initial Symptom ◽

Once Daily ◽

The Past ◽

Clostridioides Difficile ◽

Time To Recurrence ◽

Clostridioides Difficile Infection ◽

The Mean ◽

Systemic Antibiotics

Abstract Background There is a paucity of data assessing outcomes of alternate fidaxomicin strategies in patients with recurrent Clostridioides difficile infection (rCDI). The objective of our study is to evaluate a tapered-pulsed (T-P) fidaxomicin regimen that was administered immediately following a course of CDI treatment with initial symptom resolution in patients with multiple rCDI. Methods We reviewed the characteristics and outcomes of 46 consecutive patients who received T-P fidaxomicin between January 1, 2014-June 30, 2019 in a specialty CDI clinic. The first episode in which fidaxomicin T-P was administered was analyzed. Failure was defined as the persistence of diarrhea and/or the need for additional CDI treatment at any time on T-P fidaxomicin. Sustained clinical cure (SCC) was defined as resolution of diarrhea without recurrence. Recurrence was defined as the return of diarrhea requiring retreatment with CDI therapy after completion of T-P fidaxomicin. Both SCC and recurrence were evaluated at 30 and 90 days after completion of T-P fidaxomicin. Results The mean±SD age of the 46 patients was 63.2±19.9 years, 71.7% were female, and the mean±SD CDI episodes within the past year was 3±1.4 . Most patients (73.9%) had previously failed a vancomycin tapered and/or pulsed regimen. Prior to administering T-P fidaxomicin, a treatment regimen was given to ensure resolution of symptoms. The CDI treatment most commonly used (58.7%) was vancomycin. The T-P fidaxomicin regimen used consisted of 200 mg given once daily for 7 days followed by 200 mg every other day for a median (min-max) duration of 33 (6-120) days. Two patients (4%) failed to respond to T-P fidaxomicin; 34 (74%) and 28 (61%) achieved SCC at 30 and 90 days, respectively. Among the 44 patients that successfully completed the T-P fidaxomicin regimen, recurrence developed in 10 (22.7%) and 16 (36.4%) of patients at 30 and 90 days, respectively, with a median (min-max) time to recurrence of 20 (3-87) days (Figure 1). Four patients with recurrence had received subsequent systemic antibiotics. Figure 1. Course of CDI therapy and follow-up Conclusion A tapered-pulsed fidaxomicin strategy may be effective in patients with multiply rCDI who are refractory to other treatments, including a vancomycin tapered and pulsed regimen. Disclosures Larry H. Danziger, PharmD, Merck (Speaker’s Bureau)

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Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe

BMC Pharmacology and Toxicology ◽

10.1186/s40360-021-00497-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Bernard Ngara ◽

Simbarashe Zvada ◽

Tariro Dianah Chawana ◽

Charles Fungai Brian Nhachi ◽

Simbarashe Rusakaniko

Keyword(s):

Viral Load ◽

Secondary Analysis ◽

Maximal Effect ◽

Viral Load Suppression ◽

Regression Methods ◽

Pharmacodynamic Modelling ◽

Pkpd Model ◽

Drug Potency ◽

Adherence Monitoring

Abstract Background Drug potency is a pharmacological parameter defining dose or concentration of drug required to obtain 50% of the drug’s maximal effect. Pharmacokinetic-pharmacodynamic modelling and simulation allows estimation of potency and evaluate strategies improving treatment outcome. The objective of our study is to determine potency of atazanavir in hair, defined as atazanavir level in hair associated with 50% probability of failing to achieve viral load below 1000 copies/ml among adolescents, and explore the effect of participant specific variables on potency. Methods A secondary analysis was performed on data from a previous study conducted in HIV-infected adolescents failing 2nd line ART from Harare central hospital, Zimbabwe, between 2015 and 2016. We simulated atazanavir concentrations in hair using NONMEM (version 7.3) ADVAN 13, based on a previously established pharmacokinetic model. Logistic regression methods were used for PKPD analysis. Simulations utilising PKPD model focused on estimation of potency and exploring the effect of covariates. Results The potency of atazanavir in hair was found to be 4.5 ng/mg hair before adjusting for covariate effects. Participants at three months follow-up, reporting adequate adherence, having normal BMI-for-age, and cared for by mature guardians had increased potency of atazanavir in hair of 2.6 ng/mg, however the follow-up event was the only statistically significant factor at 5% level. Conclusion Atazanavir in hair in the range 2.6 to 4.5 ng/mg is associated with above 50% probability of early viral load suppression. Adherence monitoring to adolescents with lower potency of atazanavir is recommended. The effect self-reported adherence level, BMI-for-age, and caregiver status require further evaluation.

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Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis

AIDS Research and Therapy ◽

10.1186/s12981-021-00336-0 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Anita Mesic ◽

Alexander Spina ◽

Htay Thet Mar ◽

Phone Thit ◽

Tom Decroo ◽

...

Keyword(s):

Viral Load ◽

Virological Failure ◽

Antiretroviral Treatment ◽

People Living With Hiv ◽

First Line ◽

Hiv Viral Load ◽

Loss To Follow Up ◽

History Of ◽

Living With Hiv

Abstract Background Progress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar. Methods We conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months’ standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox’s regression was performed to identify risk factors for virological failure. Results We included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0–39.1) and a median observation time of 5.4 years (IQR 3.7–7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20–1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14–1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42–1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41–1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07–1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates. Conclusions VL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.

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Saliva and serum testosterone following oral testosterone undecanoate administration in normal and hypogonadal men

Acta Endocrinologica ◽

10.1530/acta.0.1020456 ◽

1983 ◽

Vol 102 (3) ◽

pp. 456-462 ◽

Cited By ~ 79

Author(s):

Th. Schürmeyer ◽

E. J. Wickings ◽

C. W. Freischem ◽

E. Nieschlag

Keyword(s):

Interindividual Variability ◽

Serum Testosterone ◽

Serum Samples ◽

Additional Increase ◽

Testosterone Undecanoate ◽

Absorption Pattern ◽

High Interindividual Variability ◽

Normal Men ◽

Hydrolysis Of ◽

Testosterone Ester

Abstract. Since saliva testosterone reflects the testosterone fraction available to target tissues the therapeutic effectiveness of orally administered testosterone undecanoate was assessed by measuring testosterone in serum and saliva. Matched saliva and serum samples were obtained from 12 normal men and 8 hypogonadal men before and at hourly intervals after the oral administration of 120 mg testosterone undecanoate. The test was repeated in 3 men after they had taken 40 mg testosterone undecanoate twice daily for 4 to 5 weeks. Following testosterone undecanoate administration serum and saliva testosterone always showed parallel increases. However, the absorption curves showed a high interindividual variability in the time when maximum concentrations were reached, as well as in the maximum levels themselves. The increases in serum and saliva testosterone were similar in normal and hypogonadal men. In normal men basal levels were reached 4 h after the maximum had occurred, while in hypogonadal men testosterone levels were not different from basal levels 2 h after the maximum. The study shows that testosterone undecanoate is well absorbed from the gut and releases significantly elevated amounts of testosterone which is available to target tissues. As the absorption pattern was always parallel in both fluids, hydrolysis of the circulating testosterone ester by the tissue ifself seems to effect no additional increase of testosterone in the tissue.

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Abstract 2276: Microhemorrhage Burden Increases the Risk of Hematoma Growth in Patients with Intracerebral Hemorrhage

Stroke ◽

10.1161/str.43.suppl_1.a2276 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Joan Martí-Fàbregas ◽

Estrella Morenas ◽

Raquel Delgado-Mederos ◽

Lavinia Dinia ◽

Esther Granell ◽

...

Keyword(s):

Differential Diagnosis ◽

Statistical Analysis ◽

Intracerebral Hemorrhage ◽

Multicentre Study ◽

Symptom Onset ◽

Variable Time ◽

Hematoma Growth ◽

Acute Intracerebral Hemorrhage ◽

Radiological Studies

Introduction Microhemorrhages (MH) are lesions detected on radiological studies resulting from an underlying small-vessel angiopathy. We assesed the hypothesis that the presence of MH increases the risk of hematoma growth (HG) in patients with acute Intracerebral Hemorrhage (ICH). Methods We evaluated a series of patients in a prospective and multicentre study. We included patients with a spontaneous supratentorial ICH within the first 6 hours after symptom onset, that also had a follow-up CT 24-72 hours later and a MRI performed after a variable time after ICH. HG was defined as an increase >33% in the volume of hematoma on the follow-up CT, in comparison with the admission CT. The volume was calculated using the formula AxBxC/2. On MR scans we assessed the presence, number and distribution of MH. After differential diagnosis with other radiological lesions, MH were evaluated on echo-gradient sequences and defined as hypointense rounded lesions with a diameter <10mm. Statistical analysis: Bivariate tests with the whole sample and with the subgroup of patients with less than 3 hours from symptom onset. Results We studied 46 patients, whose mean age was 68.8±11.2 y and 68% were men. Mean baseline volume was 19.1±27.3 cc. We detected MH in 7/15 patients with HG and in 18/31 patients without HG (46.7% vs 58.1%, p=0.53). In the subgroup of patients with 10 MH, the risk of HG was higher than in patients with 0-10 MH (75% vs 28.6%, p=0.067), and this difference was significant when considering only patients with a <3 hours evolution (100% vs 31%, p=0.044). We did not observe any association between risk of HG and distribution of MH. Age and time to CT were equivalent in the two groups (with and without HG), either in the <6 or <3 hours subgroups. Conclusions In conclusion, in patients with hyperacute ICH, the presence of more than 10 MH increases the risk of HG. This is probably an indirect marker of a more severe underlying angiopathy.

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