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American Journal of Obstetrics &... Oct 2023This study aimed to evaluate the natural history of selective intrauterine growth restriction in monochorionic twin pregnancies based on the Gratacós classification,... (Meta-Analysis)
Meta-Analysis Review
Selective intrauterine growth restriction without concomitant twin-to-twin transfusion syndrome, natural history, and risk factors for fetal death: A systematic review and meta-analysis.
OBJECTIVE
This study aimed to evaluate the natural history of selective intrauterine growth restriction in monochorionic twin pregnancies based on the Gratacós classification, including progression of, improvement in, or stability of umbilical artery Dopplers and progression to twin-to-twin transfusion syndrome or twin anemia polycythemia syndrome. We also aimed to investigate risk factors for smaller twin demise.
DATA SOURCES
A systematic search was performed to identify relevant studies published in English up to June 2022 using the databases PubMed, Scopus, and Web of Science STUDY ELIGIBILITY: We used retrospective and prospective studies published in English that reported on selective intrauterine growth restriction without concomitant twin-to-twin transfusion syndrome.
STUDY APPRAISAL AND SYNTHESIS METHODS
Articles that investigated selective intrauterine growth restriction progression and outcomes by umbilical artery Doppler end-diastolic flow (Gratacós classification) were included. Type I included selective intrauterine growth restriction cases with positive end-diastolic flow, type II included those cases with persistently absent end-diastolic flow, and type III included cases with intermittent absent or reversed end-diastolic flow. Pregnancies in which a diagnosis of twin-to-twin transfusion syndrome or twin anemia polycythemia sequence was made before the diagnosis of selective intrauterine growth restriction were not included in the analysis. A random effects model was used to pool the odds ratios and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I value.
RESULTS
A total of 17 studies encompassing 2748 monochorionic pregnancies complicated by selective intrauterine growth restriction were included in the analysis. The incidence of stable, deteriorating, or improving umbilical artery Dopplers in type I cases was 68% (95% confidence interval, 26-89), 23% (95% confidence interval, 7-40), and 9% (95% confidence interval, 0.0-100), respectively. In type II cases, the incidence was 40% (95% confidence interval, 18-81), 50% (95% confidence interval, 23-82), and 10% (95% confidence interval, 4-37), respectively, and in type III cases, the incidence was 55% (95% confidence interval, 2-99), 23% (95% confidence interval, 9-43), and 22% (95% confidence interval, 6-54), respectively. The risk for progression to twin-to-twin transfusion syndrome was comparable between type I (7%) and type III (9%) cases and occurred in 4% (95% confidence interval, 0-67) of type II cases with no significant subgroup differences. Progression to twin anemia polycythemia syndrome was highest in type I cases (12%) and comparable between type II (2%) and III (1%) cases with no significant subgroup differences. Risk factors for smaller twin demise were earlier gestational age at diagnosis (mean difference, -2.69 weeks; 95% confidence interval, -4.94 to -0.45; I, 45%), larger intertwin weight discordance (mean difference, 34%; 95% confidence interval, 1.35-5.38; I, 28%), deterioration of umbilical artery Dopplers for each of type II and III cases (odds ratio, 3.05; 95% confidence interval, 1.36-6.84; I, 24%; and odds ratio, 4.5; 95% confidence interval, 2.31-8.77; I, 0.0%, respectively), and absent or reversed ductus venosus a-wave for each of type II and III cases (odds ratio, 3.35; 95% confidence interval, 2.28-4.93; I, 0.0%; and odds ratio, 2.36; 95% confidence interval, 1.08-5.13; I, 0.0%, respectively). Progression to twin-to-twin transfusion syndrome was not significantly associated with smaller twin demise for each of type II and III selective intrauterine growth restriction cases.
CONCLUSION
These findings improve our understanding of the natural history of the types of selective intrauterine growth restriction and of the predictors of smaller twin demise in type II and III selective intrauterine growth restriction cases. The current data provide vital counseling points and support the need for modifications of the current selective intrauterine growth restriction classification system to include the variations in umbilical artery and ductus venosus Dopplers to better identify a cohort that might benefit from fetal intervention for which future multicenter prospective randomized trials are needed.
Topics: Pregnancy; Female; Humans; Infant, Newborn; Fetofetal Transfusion; Fetal Growth Retardation; Prospective Studies; Retrospective Studies; Polycythemia; Fetal Death; Risk Factors; Multicenter Studies as Topic
PubMed: 37527736
DOI: 10.1016/j.ajogmf.2023.101105 -
Ultrasound in Obstetrics & Gynecology :... Dec 2021To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS), according to the type of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS), according to the type of TAPS (spontaneous or postlaser) and the management option adopted.
METHODS
MEDLINE, EMBASE and The Cochrane Library databases were searched for studies reporting on the outcome of twin pregnancies complicated by TAPS. Inclusion criteria were non-anomalous MCDA twin pregnancies with a diagnosis of TAPS. The primary outcome was perinatal mortality; secondary outcomes were neonatal morbidity and preterm birth (PTB). The outcomes were stratified according to the type of TAPS (spontaneous or following laser treatment for twin-twin transfusion syndrome) and the management option adopted (expectant, laser surgery, intrauterine transfusion (IUT) or selective reduction (SR)). Random-effects meta-analysis of proportions was used to analyze the data.
RESULTS
Perinatal outcome was assessed according to whether TAPS occurred spontaneously or after laser treatment in 506 pregnancies (38 studies). Intrauterine death (IUD) occurred in 5.2% (95% CI, 3.6-7.1%) of twins with spontaneous TAPS and in 10.2% (95% CI, 7.4-13.3%) of those with postlaser TAPS, while the corresponding rates of neonatal death were 4.0% (95% CI, 2.6-5.7%) and 9.2% (95% CI, 6.6-12.3%), respectively. Severe neonatal morbidity occurred in 29.3% (95% CI, 25.6-33.1%) of twins after spontaneous TAPS and in 33.3% (95% CI, 17.4-51.8%) after postlaser TAPS, while the corresponding rates of severe neurological morbidity were 4.0% (95% CI, 3.5-5.7%) and 11.1% (95% CI, 6.2-17.2%), respectively. PTB complicated 86.3% (95% CI, 77.2-93.3%) of pregnancies with spontaneous TAPS and all cases with postlaser TAPS (100% (95% CI, 84.3-100%)). Iatrogenic PTB was more frequent than spontaneous PTB in both groups. Perinatal outcome was assessed according to the management option adopted in 417 pregnancies (21 studies). IUD occurred in 9.8% (95% CI, 4.3-17.1%) of twins managed expectantly and in 13.1% (95% CI, 9.2-17.6%), 12.1% (95% CI, 7.7-17.3%) and 7.6% (95% CI, 1.3-18.5%) of those treated with laser surgery, IUT and SR, respectively. Severe neonatal morbidity affected 27.3% (95% CI, 13.6-43.6%) of twins in the expectant-management group, 28.7% (95% CI, 22.7-35.1%) of those in the laser-surgery group, 38.2% (95% CI, 18.3-60.5%) of those in the IUT group and 23.3% (95% CI, 10.5-39.2%) of those in the SR group. PTB complicated 80.4% (95% CI, 59.8-94.8%), 73.4% (95% CI, 48.1-92.3%), 100% (95% CI, 76.5-100%) and 100% (95% CI, 39.8-100%) of pregnancies after expectant management, laser surgery, IUT and SR, respectively.
CONCLUSIONS
The present meta-analysis provides pooled estimates of the risks of perinatal mortality, neonatal morbidity and PTB in twin pregnancies complicated by TAPS, stratified by the type of TAPS and the management option adopted. Although a direct comparison could not be performed, the results from this systematic review suggest that spontaneous TAPS may have a better prognosis than postlaser TAPS. No differences in terms of mortality and morbidity were observed when comparing different management options for TAPS, although these findings should be interpreted with caution in view of the limitations of the included studies. Individualized prenatal management, taking into account the severity of TAPS and gestational age, is currently the recommended strategy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Anemia, Neonatal; Blood Transfusion, Intrauterine; Diseases in Twins; Female; Fetal Diseases; Fetal Therapies; Fetofetal Transfusion; Gestational Age; Humans; Infant, Newborn; Laser Therapy; Perinatal Mortality; Polycythemia; Pregnancy; Pregnancy Outcome; Pregnancy, Twin; Premature Birth; Prognosis
PubMed: 33428243
DOI: 10.1002/uog.23585 -
Haematologica Dec 2019Hydroxyurea is the standard treatment in high-risk patients with polycythemia vera. However, estimates of its effect in terms of clinical outcomes (thrombosis, bleeding,... (Meta-Analysis)
Meta-Analysis
Hydroxyurea is the standard treatment in high-risk patients with polycythemia vera. However, estimates of its effect in terms of clinical outcomes (thrombosis, bleeding, hematologic transformations and mortality) are lacking. We performed a meta-analysis to determine the absolute risk of events in recent cases of patients under hydroxyurea treatment. We searched for relevant articles or abstracts in the following databases: Medline, EMBASE, clinicaltrials.gov, WHO International Clinical Trials Registry, LILACS. Sixteen studies published from 2008 to 2018 reporting number of events using World Health Organization diagnosis for polycythemia vera were selected. Through a random effect logistic model, incidences, study heterogeneity and confounder effects were estimated for each outcome at different follow ups. Overall, 3,236 patients were analyzed. While incidences of thrombosis and acute myeloid leukemia were stable over time, mortality and myelofibrosis varied depending on follow-up duration. Thrombosis rates were 1.9%, 3.6% and 6.8% persons/year at median ages 60, 70 and 80 years, respectively. Higher incidence of arterial events was predicted by previous cardiovascular complication. Leukemic transformation incidence was 0.4% persons/year. Incidence of transformation to myelofibrosis and mortality were significantly dependent on age and follow-up duration. For myelofibrosis, rates were 5.0 at five years and 33.7% at ten years; overall mortality was 12.6% and 56.2% at five and ten years, respectively. In conclusion, we provide reliable risk estimates for the main outcomes in polycythemia vera patients under hydroxyurea treatment. These findings can help design comparative clinical trials with new cytoreductive drugs and prove the feasibility of using critical end points for efficacy, such as major thrombosis.
Topics: Hemorrhage; Humans; Hydroxyurea; Polycythemia Vera; Primary Myelofibrosis; Prognosis; Risk Factors; Survival Rate; Thrombosis
PubMed: 31123026
DOI: 10.3324/haematol.2019.221234 -
African Journal of Reproductive Health Nov 2023We compare the hematocrit, hemoglobin, need for transfusion, recurrent phototherapy, serum bilirubin level, and serum ferritin at different time frames for the umbilical... (Meta-Analysis)
Meta-Analysis
Comparing the safety and effectiveness of various umbilical cord milking techniques and delayed cord clamping in full-term and preterm infants: A systematic review and meta-analysis.
We compare the hematocrit, hemoglobin, need for transfusion, recurrent phototherapy, serum bilirubin level, and serum ferritin at different time frames for the umbilical cord milking (UCM) and delayed cord clamping (DCC) in both full-term and preterm infants. A comprehensive search through various databases aimed to compare UCM and DCC studies until May 2nd, 2023. Cochrane and NIH tools assessed RCTs and cohorts, respectively. Meta-analysis employed Review Manager 5.4 software, calculating MD and RR with 95% CIs for continuous and dichotomous data. We included 20 studies with a total of 5189 infants. Regarding preterm infants, hematocrit level showed no significant difference between intact Umbilical Cord Milking (iUCM) compared to DCC (MD = -0.24, 95% CI [-1.11, 0.64]). Moreover, Neonatal death incidence was significantly higher with the UCM technique in comparison to DCC (RR = 1.28, 95% CI [1.01 to 1.62]). Regarding term and late preterm infants, Hematocrit level showed no significant difference between the iUCM or cUCM techniques compared to DCC (MD = 0.21, 95% CI [-1.28 to 1.69]), (MD = 0.96, 95% CI [-1.02 to 2.95]), respectively. UCM led to a higher risk of neonatal death in preterm infants compared to DCC. However, the incidence of polycythemia was lower in the UCM group. Additionally, UCM was associated with higher rates of severe IVH events. Based on these findings, DCC may be preferred due to its lower incidence of severe IVH and neonatal death.
Topics: Infant; Pregnancy; Female; Infant, Newborn; Humans; Infant, Premature; Umbilical Cord Clamping; Perinatal Death; Umbilical Cord; Hematocrit
PubMed: 38053339
DOI: 10.29063/ajrh2023/v27i11.11 -
Laryngoscope Investigative... Apr 2022The aim of this systematic review and meta-analysis was to investigate the association between obstructive sleep apnea (OSA) and erythrocytosis. (Review)
Review
OBJECTIVE
The aim of this systematic review and meta-analysis was to investigate the association between obstructive sleep apnea (OSA) and erythrocytosis.
METHODS
The PubMed, Web of Science, and Cochrane Library databases were searched for articles examining hematocrit values in patients with OSA and control individuals published till September 1, 2021. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated, and subgroup analyses were performed.
RESULTS
Eleven eligible studies with a total of 4608 patients with OSA were included in this meta-analysis. Pooled outcomes revealed that hematocrit values were significantly higher in patients with OSA than in controls (SMD, 0.19; 95% CI, 0.08-0.29; < .01). When studies were stratified by disease severity, the significant differences in hematocrit values between patients and controls were only observed in the severe OSA group (SMD, 0.34; 95% CI, 0.08-0.59; < .01), but not in the mild and moderate OSA groups. In subgroup analyses according to sex and publication year, significant differences in hematocrit values between patients and controls remained stable in studies with only female patients (SMD, 0.25; 95% CI, 0.12-0.38; < .01) and in studies published after 2012 (SMD, 0.17; 95% CI, 0.06-0.28, < .01).
CONCLUSION
Our meta-analysis revealed that the hematocrit value was significantly increased in patients with OSA, particularly in severe patients, compared with that in controls. However, the elevation was modest, and the hematocrit value is expected to be within the normal range in patients with OSA. These data suggest that OSA leads to slight increases in hematocrit but does not cause clinically significant erythrocytosis.
PubMed: 35434329
DOI: 10.1002/lio2.751 -
Journal of Obstetrics and Gynaecology... Aug 2014To analyze outcomes of monochorionic twins with twin anemia-polycythemia sequence (TAPS). (Review)
Review
OBJECTIVE
To analyze outcomes of monochorionic twins with twin anemia-polycythemia sequence (TAPS).
DATA SOURCES
PubMed, EMBASE, Medline, and reference list.
STUDY SELECTION
We included reports of TAPS defined prenatally with abnormal Doppler studies of middle cerebral artery and normal amniotic fluid volume which reported data as proportional rates.
DATA EXTRACTION
Abstracted outcomes were postnatal hemoglobin levels, postnatal procedures, and survival rates. Outcomes were analyzed for gestational age at diagnosis of TAPS (15 to 23 weeks, 24 to 29 weeks, > 29 weeks), in utero therapy, and nature of onset (isolated TAPS, or following twin-to-twin transfusion syndrome). The review was performed using MOOSE guidelines. Differences were significant if P < 0.05.
DATA SYNTHESIS
We assessed data on 28 pregnancies with TAPS. Diagnosis at 15 to 23 weeks' gestation and in utero therapy were associated with the highest mean levels of hemoglobin in anemic twins (P = 0.021), the lowest levels in polycythemic twins (P = 0.025), and the lowest frequency of postnatal procedures (P < 0.001). Survival rate was independent of gestational age at diagnosis and in utero therapy. In cases of TAPS following twin-to-twin transfusion, the mean hemoglobin level was higher in donors than in anemic twins with isolated TAPS (P = 0.029) and similar between recipients and polycythemic twins with isolated TAPS (P = 0.135). Twins with TAPS following twin-to-twin transfusion received in utero therapy more frequently than isolated TAPS twins (P = 0.030) and required a postnatal procedure less often (P < 0.001). Survival rates were similar in each group.
CONCLUSION
Diagnosis of TAPS at an early gestational age is associated with more favourable outcomes than later diagnosis. In utero therapy improves neonatal hemoglobin levels but does not change survival rates. Previous twin-to-twin transfusion syndrome does not worsen outcomes.
Topics: Female; Fetofetal Transfusion; Gestational Age; Hemoglobins; Humans; Pregnancy; Pregnancy Outcome; Prenatal Diagnosis
PubMed: 25222165
DOI: 10.1016/S1701-2163(15)30512-0 -
The Journal of Sexual Medicine Jan 2013Testosterone (T) deficiency (TD) may significantly affect sexual function and multiple organ systems. (Review)
Review
INTRODUCTION
Testosterone (T) deficiency (TD) may significantly affect sexual function and multiple organ systems.
AIM
To provide recommendations and Standard Operating Procedures (SOPs) based on best evidence for diagnosis and treatment of TD in men.
METHODS
Medical literature was reviewed by the Endocrine subcommittee of the ISSM Standards Committee, followed by extensive internal discussion over two years, then public presentation and discussion with other experts.
MAIN OUTCOME MEASURE
Recommendations and SOPs based on grading of evidence-based medical literature and interactive discussion.
RESULTS
TD is the association of a low serum T with consistent symptoms or signs. T level tends to decline with age. T modulates sexual motivation and erection. It also plays a broader role in men's health. Recent studies have established associations between low T, male sexual dysfunctions and metabolic risk factors. Though association does not mean causation, low T is associated with reduced longevity, risk of fatal cardiovascular events, obesity, sarcopenia, mobility limitations, osteoporosis, frailty, cognitive impairment, depression, Sleep Apnea Syndrome, and other chronic diseases. The paper proposes a standardized process for diagnosis and treatment of TD, and updates the knowledge on T therapy (Tth) and prostate and cardiovascular safety. There is no compelling evidence that Tth causes prostate cancer or its progression in men without severe TD. Polycythemia is presently the only cardiovascular-related adverse-event significantly associated with Tth. But follow-up of controlled T trials is limited to 3 years.
CONCLUSIONS
Men with sexual dysfunctions, and/or with visceral obesity and metabolic diseases should be screened for TD and treated. Young men with TD should also be treated. Benefits and risks of Tth should be carefully assessed in older men. Prospective, long-term, placebo-controlled, interventional studies are required before screening for TD in more conditions, including cardiovascular diseases, and considering correction of TD as preventive medicine.
Topics: Cardiovascular Diseases; Clinical Laboratory Techniques; Clinical Protocols; Humans; Male; Practice Guidelines as Topic; Testosterone
PubMed: 22971200
DOI: 10.1111/j.1743-6109.2012.02783.x -
Acta Paediatrica (Oslo, Norway : 1992) Nov 2005To determine whether crystalloid solutions are as effective as colloid solutions when a partial exchange transfusion is performed in newborns with polycythemia. (Meta-Analysis)
Meta-Analysis Review
AIMS
To determine whether crystalloid solutions are as effective as colloid solutions when a partial exchange transfusion is performed in newborns with polycythemia.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register of the Cochrane Library (1966-2004). Keywords used were: polycythemia, partial exchange transfusion, hyperviscosity, and limited to newborn. Randomized studies in newborns with polycythemia were selected for evaluation. Outcomes examined were: long-term neurodevelopment; short-term physiological effects; improvement in clinical symptoms; reduction in haematocrit at 4-6 h; haematocrit at 24 h; and frequency of serious complications.
RESULTS
Four randomized controlled clinical trials, including 200 patients in total, with evaluable data, which satisfied our criteria, were found. There were no data on long-term outcomes. There is no reported important difference in short-term physiologic effects. Use of crystalloid was as effective as colloid in both correction of haematological values and reduction of clinical symptoms following partial exchange transfusion.
CONCLUSION
Crystalloid solutions are as effective as colloid solutions for partial exchange transfusion. When crystalloid solutions are used for this purpose, there is no risk of transmission of blood-borne diseases, there is no risk of anaphylaxis, they are rapidly and easily available, and are less expensive. The use of crystalloid should become the standard for partial exchange transfusion.
Topics: Colloids; Crystalloid Solutions; Exchange Transfusion, Whole Blood; Humans; Infant, Newborn; Isotonic Solutions; Polycythemia; Treatment Outcome
PubMed: 16303705
DOI: 10.1080/08035250500192748 -
American Journal of Hematology Mar 2018Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of... (Meta-Analysis)
Meta-Analysis
Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib. Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI). Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N = 10), hepatitis B reactivation (N = 5) and pneumocystis jeroveci infection (N = 2). Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy.
Topics: Antibiotic Prophylaxis; Bacterial Infections; Clinical Trials, Phase III as Topic; Confidence Intervals; Disease Susceptibility; Herpes Zoster; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Infections; Janus Kinase 1; Janus Kinase 2; Mycoses; Nitriles; Odds Ratio; Product Surveillance, Postmarketing; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Risk
PubMed: 29150886
DOI: 10.1002/ajh.24976 -
Haematologica Aug 2019Although it is well known that myeloproliferative neoplasms occur in younger patients, few large cohorts of such patients have been reported. Thus, our knowledge about...
Although it is well known that myeloproliferative neoplasms occur in younger patients, few large cohorts of such patients have been reported. Thus, our knowledge about circumstances of diagnosis, outcome and treatment is limited, especially for children and young adults. We therefore performed a systematic review of cases, published since 2005, concerning patients aged below 20 years at the time of diagnosis of essential thrombocythemia or polycythemia vera. We identified 396 cases of essential thrombocythemia and 75 of polycythemia vera. The median age at diagnosis was 9.3 and 12 years, respectively, and females constituted 57.6% and 45% of the groups, respectively. Half of the patients were asymptomatic at diagnosis. The proportion of so-called triple negativity was high: 57% in essential thrombocythemia and 73% in polycythemia vera. The incidence of thrombosis during the follow-up was 9.3% in patients with polycythemia vera and less, 3.8%, in those with essential thrombocythemia. Venous events were predominant (84.2%), with hemorrhagic episodes being rarer (<5%). The risk of evolution also seemed low (2% to myelofibrosis and no reports of acute leukemia), but the median follow-up was only 50 months. Survival curves were not available. Half of the patients received an antithrombotic drug and 40.5% received a cytoreductive drug. All data should be analyzed with care because of the proportion of missing data (10.7% to 74.7%). This review highlights interesting points concerning this population of young patients with myeloproliferative neoplasms, including that such patients were identified as negative for all common driver mutations, but also shows the need for larger contemporary cohorts with longer follow-up to assess the true prognosis of these patients.
Topics: Adolescent; Asymptomatic Diseases; Child; Cytotoxins; Early Diagnosis; Fibrinolytic Agents; Gene Expression; Hemorrhage; Humans; Janus Kinase 1; Janus Kinase 2; Mutation; Polycythemia Vera; Prognosis; Splenomegaly; Thrombocythemia, Essential; Thrombosis; Young Adult
PubMed: 30679326
DOI: 10.3324/haematol.2018.200832