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Journal of Obstetrics and Gynaecology... Jul 2019Twin anemia-polycythemia sequence (TAPS) is a complication of monochorionic, multiple gestation pregnancies in which blood shunting through placental anastomoses results...
BACKGROUND
Twin anemia-polycythemia sequence (TAPS) is a complication of monochorionic, multiple gestation pregnancies in which blood shunting through placental anastomoses results in chronic anemia in one fetus and chronic polycythemia in another. The outcomes of different treatment modalities for TAPS are not well known.
OBJECTIVE
To determine the outcomes of the intrauterine interventions used to treat TAPS.
STUDY DESIGN
A systematic literature search of MEDLINE, EMBASE, and CENTRAL was performed in June 2016. Primary outcomes were mortality, morbidity, and adverse perinatal outcomes. Data were summarized in the form of weighted means, and statistical difference was determined.
RESULTS
Twenty-one articles were identified for inclusion in this review and were composed of 105 cases of TAPS. In the cases presented in the literature, there was no statistically significant difference in mortality, morbidity, or emergent Caesarean section rates between expectant management, intrauterine transfusion (IUT), and laser ablation therapy. Laser ablation therapy and IUT were found to have a significantly lower rate of adverse perinatal outcomes when compared to expectantly managed cases.
CONCLUSIONS
The literature looking into the treatment of TAPS is very limited, with no randomized controlled trials and only one includable comparative study. Based on the data in the case report and case study literature, there is no mortality difference between any of the treatment modalities. Expectant management may be associated with an increase in adverse perinatal outcomes when compared to laser therapy and IUT. More comparative studies are needed to assist clinicians in adopting an evidence-based approach to the treatment of TAPS.
Topics: Female; Fetofetal Transfusion; Humans; Pregnancy; Pregnancy, Twin; Ultrasonography, Prenatal
PubMed: 31230662
DOI: 10.1016/j.jogc.2018.04.005 -
BMC Cancer Jun 2019Research into Philadelphia-negative chronic myeloproliferative neoplasms is heterogeneous. In addition, no systematization of studies of polycythemia vera (PV),... (Meta-Analysis)
Meta-Analysis
Systematization of analytical studies of polycythemia vera, essential thrombocythemia and primary myelofibrosis, and a meta-analysis of the frequency of JAK2, CALR and MPL mutations: 2000-2018.
BACKGROUND
Research into Philadelphia-negative chronic myeloproliferative neoplasms is heterogeneous. In addition, no systematization of studies of polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF) have been carried out. The objective of this review is to characterize studies on BCR-ABL1-negative chronic myeloproliferative neoplasms and to compare the frequency of JAK2, MPL and CALR mutations in PV, ET and PMF.
METHOD
A systematic review of the scientific literature was conducted, as was meta-analysis with an ex-ante selection of protocol, according to phases of the PRISMA guide in three interdisciplinary databases. To guarantee reproducibility in the pursuit and retrieval of information, the reproducibility and methodological quality of the studies were evaluated by two researchers.
RESULTS
Fifty-two studies were included, the majority having been carried out in the United States, China, Brazil and Europe. The frequency of the JAK2V617F mutation ranged from 46.7 to 100% in patients with PV, from 31.3 to 72.1% in patients with ET, and from 25.0 to 85.7% in those with PMF. The frequency of the MPL mutation was 0% in PV, from 0.9 to 12.5% in ET, and from 0 to 17.1% in PMF. The CALR mutation occurred at a frequency of 0.0% in PV, whereas in ET, it ranged from 12.6 to 50%, and in PMF, it ranged from 10 to 100%. The risk of this mutation presenting in PV is 3.0 times that found for ET and 4.0 times that found for PMF.
CONCLUSION
Given the specificity and reported high frequencies of the JAK2V617F, MPL and CALR mutations in this group of neoplasms, the diagnosis of these diseases should not be made on clinical and hematological characteristics alone but should include genetic screening of patients.
Topics: Biomarkers, Tumor; Calreticulin; Genetic Heterogeneity; Genetic Testing; Humans; Janus Kinase 2; Mutation Rate; Oncogene Proteins, Fusion; Polycythemia Vera; Primary Myelofibrosis; Receptors, Thrombopoietin; Reproducibility of Results; Thrombocythemia, Essential
PubMed: 31208359
DOI: 10.1186/s12885-019-5764-4 -
Blood Advances Jun 2019In the last years, a growing amount of evidence has been produced regarding the role of leukocytosis as a risk factor for thrombosis in patients with myeloproliferative... (Meta-Analysis)
Meta-Analysis
In the last years, a growing amount of evidence has been produced regarding the role of leukocytosis as a risk factor for thrombosis in patients with myeloproliferative neoplasms, predominantly in polycythemia vera (PV) and essential thrombocythemia (ET). Results from epidemiologic studies on this issue, however, are inconclusive. We conducted a systematic review and meta-analysis of articles published in the last 12 years addressing the issue, according to a predefined protocol. Forty-one articles analyzing >30 000 patients met our inclusion criteria and were deemed of acceptable methodologic quality. In addition to data on thrombosis, data were collected on bleeding, hematologic evolution, secondary cancer, and death. The relative risk (RR) of thrombosis in the presence of leukocytosis was 1.59 (95% CI, 1.40-1.80), mainly accounted for by ET (RR, 1.65; 95% CI, 1.43-1.91) and arterial thrombosis (RR, 1.45; 95% CI, 1.13-1.86) subgroups; the effect was not significant in venous thrombosis alone. Sensitivity analyses considering recurrent events as well as white blood cell estimates adjusted or unadjusted for confounding factors confirmed the primary results. In addition, the pooled RR of studies that tested white blood cell counts in time-dependent models suggested a causative effect of leukocytes in the mechanism that triggers thrombosis. The effect of leukocytosis on bleeding (RR, 1.87; 95% CI, 1.26-2.77) and death (RR, 1.89; 95% CI, 1.59-2.23) was confirmed, whereas conclusions on hematologic evolutions and solid tumors were uncertain. To confirm the accuracy of these results, an investigation on individual patient data in a large collective archive of homogeneous patients is warranted.
Topics: Female; Hemorrhage; Humans; Leukocytosis; Male; Polycythemia Vera; Risk Factors; Thrombocythemia, Essential; Thrombosis
PubMed: 31175128
DOI: 10.1182/bloodadvances.2019000211 -
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 -
BMC Cancer Feb 2019Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem cell clonal diseases. Most patients with MPN... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem cell clonal diseases. Most patients with MPN are asymptomatic at diagnosis although some of them suffer from constitutional symptoms. Thrombosis and bleeding can also be one of the initial manifestations although the reported prevalence varied considerably across the studies. This systematic review and meta-analysis was conducted with the aims to better understand the prevalence and characteristics of thrombosis and bleeding among patients with newly-diagnosed MPN.
METHODS
Using a search strategy that included the terms for myeloproliferative neoplasms, thrombosis, and bleeding, two investigators independently searched for published articles indexed in the MEDLINE and EMBASE databases from inception to August 2018. The pooled prevalence was calculated using the DerSimonian-Laird random-effects model with a double arcsine transformation.
RESULTS
A total of 29 cohort studies (8 prospective and 21 retrospective) with 13,436 patients with MPN were included into this meta-analysis. At diagnosis, the pooled prevalence of overall thrombosis among patients with MPN was 20.0% (95% CI, 16.6-23.8%; I 96%), with the pooled prevalence of arterial thrombosis of 16.2% (95% CI, 13.0-20.0%; I 95%) and the pooled prevalence of venous thrombosis of 6.2% (95% CI, 4.9-7.8%; I 89%). Common thrombotic events included cerebrovascular disease/transient ischemic attack, coronary heart disease, and deep venous thrombosis. The pooled prevalence of hemorrhagic complications among patients who were newly diagnosed with MPN patients was 6.2% (95% CI, 5.0-7.8%; I 85%). Common sites of bleeding included gastrointestinal, mucosal, and cutaneous bleeding.
CONCLUSIONS
Thrombosis and bleeding are common initial manifestations of MPN. Investigations for MPN should be considered for patients who present with unexplained thrombosis or abnormal bleeding.
Topics: Hemorrhage; Humans; Myeloproliferative Disorders; Philadelphia Chromosome; Prevalence; Thrombosis
PubMed: 30819138
DOI: 10.1186/s12885-019-5387-9 -
The Cochrane Database of Systematic... Feb 2019Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With expectant management, signs of placental separation are awaited and the placenta is delivered spontaneously. Active management was introduced to try to reduce haemorrhage, a major contributor to maternal mortality in low-income countries. This is an update of a review last published in 2015.
OBJECTIVES
To compare the effects of active versus expectant management of the third stage of labour on severe primary postpartum haemorrhage (PPH) and other maternal and infant outcomes.To compare the effects of variations in the packages of active and expectant management of the third stage of labour on severe primary PPH and other maternal and infant outcomes.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the World health Organization International Clinical Trials Registry Platform (ICTRP), on 22 January 2018, and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing active versus expectant management of the third stage of labour. Cluster-randomised trials were eligible for inclusion, but none were identified.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the studies for inclusion, assessed risk of bias, carried out data extraction and assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
We included eight studies, involving analysis of data from 8892 women. The studies were all undertaken in hospitals, seven in higher-income countries and one in a lower-income country. Four studies compared active versus expectant management, and four compared active versus a mixture of managements. We used a random-effects model in the analyses because of clinical heterogeneity. Of the eight studies included, we considered three studies as having low risk of bias in the main aspects of sequence generation, allocation concealment and completeness of data collection. There was an absence of high-quality evidence according to GRADE assessments for our primary outcomes, which is reflected in the cautious language below.The evidence suggested that, for women at mixed levels of risk of bleeding, it is uncertain whether active management reduces the average risk of maternal severe primary PPH (more than 1000 mL) at time of birth (average risk ratio (RR) 0.34, 95% confidence interval (CI) 0.14 to 0.87, 3 studies, 4636 women, I = 60%; GRADE: very low quality). For incidence of maternal haemoglobin (Hb) less than 9 g/dL following birth, active management of the third stage may reduce the number of women with anaemia after birth (average RR 0.50, 95% CI 0.30 to 0.83, 2 studies, 1572 women; GRADE: low quality). We also found that active management of the third stage may make little or no difference to the number of babies admitted to neonatal units (average RR 0.81, 95% CI 0.60 to 1.11, 2 studies, 3207 infants; GRADE: low quality). It is uncertain whether active management of the third stage reduces the number of babies with jaundice requiring treatment (RR 0.96, 95% CI 0.55 to 1.68, 2 studies, 3142 infants, I = 66%; GRADE: very low quality). There were no data on our other primary outcomes of very severe PPH at the time of birth (more than 2500 mL), maternal mortality, or neonatal polycythaemia needing treatment.Active management reduces mean maternal blood loss at birth and probably reduces the rate of primary blood loss greater than 500 mL, and the use of therapeutic uterotonics. Active management also probably reduces the mean birthweight of the baby, reflecting the lower blood volume from interference with placental transfusion. In addition, it may reduce the need for maternal blood transfusion. However, active management may increase maternal diastolic blood pressure, vomiting after birth, afterpains, use of analgesia from birth up to discharge from the labour ward, and more women returning to hospital with bleeding (outcome not pre-specified).In the comparison of women at low risk of excessive bleeding, there were similar findings, except it was uncertain whether there was a difference identified between groups for severe primary PPH (average RR 0.31, 95% CI 0.05 to 2.17; 2 studies, 2941 women, I = 71%), maternal Hb less than 9 g/dL at 24 to 72 hours (average RR 0.17, 95% CI 0.02 to 1.47; 1 study, 193 women) or the need for neonatal admission (average RR 1.02, 95% CI 0.55 to 1.88; 1 study, 1512 women). In this group, active management may make little difference to the rate of neonatal jaundice requiring phototherapy (average RR 1.31, 95% CI 0.78 to 2.18; 1 study, 1447 women).Hypertension and interference with placental transfusion might be avoided by using modifications to the active management package, for example, omitting ergot and deferring cord clamping, but we have no direct evidence of this here.
AUTHORS' CONCLUSIONS
Although the data appeared to show that active management reduced the risk of severe primary PPH greater than 1000 mL at the time of birth, we are uncertain of this finding because of the very low-quality evidence. Active management may reduce the incidence of maternal anaemia (Hb less than 9 g/dL) following birth, but harms such as postnatal hypertension, pain and return to hospital due to bleeding were identified.In women at low risk of excessive bleeding, it is uncertain whether there was a difference between active and expectant management for severe PPH or maternal Hb less than 9 g/dL (at 24 to 72 hours). Women could be given information on the benefits and harms of both methods to support informed choice. Given the concerns about early cord clamping and the potential adverse effects of some uterotonics, it is critical now to look at the individual components of third-stage management. Data are also required from low-income countries.It must be emphasised that this review includes only a small number of studies with relatively small numbers of participants, and the quality of evidence for primary outcomes is low or very low.
Topics: Birth Weight; Constriction; Delivery, Obstetric; Female; Humans; Infant, Newborn; Jaundice, Neonatal; Labor Stage, Third; Oxytocics; Placenta; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic; Watchful Waiting
PubMed: 30754073
DOI: 10.1002/14651858.CD007412.pub5 -
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 -
Birth (Berkeley, Calif.) Sep 2019Enhanced placental transfusion reduces adverse neonatal outcomes, including death. Despite being endorsed by the World Health Organization in 2012, the method has not...
BACKGROUND
Enhanced placental transfusion reduces adverse neonatal outcomes, including death. Despite being endorsed by the World Health Organization in 2012, the method has not been adopted widely in practice.
METHODS
We performed a systematic literature search and included quality improvement projects on placental transfusion at birth and studies on barriers to implementation. We extracted information on population, methods of implementation, obstacles to implementation, and strategies to overcome them.
RESULTS
We screened 99 studies out of which 18 were included in the review. The preferred methods of implementation were protocol development (86% of studies) reinforced by targeted education (64% of studies) and multidisciplinary team involvement (43% of studies). Barriers to implementation were mentioned in 12 studies and divided into four categories: general factors such as lack of staff awareness (5 studies) and professional resistance to change (5 studies); obstetrician-specific concerns, including the impact during cesarean (3 studies) and the risk of postpartum hemorrhage (3 studies); pediatrician-specific concerns, including the need for resuscitation (5 studies), risk of jaundice (3 studies), and polycythemia (2 studies); and logistical difficulties. The main strategies to facilitate placental transfusion at birth included effective multidisciplinary team collaboration, protocol development, targeted education, and constructive feedback sessions.
CONCLUSIONS
Placental transfusion implementation requires a multidisciplinary approach, with obstetricians, midwives, nurses, and pediatricians central to adoption of the practice. Understanding the obstacles to implementation informs strategies to increase placental transfusion adoption of practice worldwide. We suggest a stepwise approach to implementation and enhancement of placental transfusion into practice.
Topics: Blood Transfusion; Constriction; Delivery, Obstetric; Female; Health Knowledge, Attitudes, Practice; Humans; Infant, Newborn; Patient Care Team; Placenta; Pregnancy; Umbilical Cord
PubMed: 30264508
DOI: 10.1111/birt.12398 -
Journal of Nuclear Medicine : Official... Mar 2019We performed a systematic review and metaanalysis of the performance of Ga-DOTA-conjugated somatostatin receptor-targeting peptide (Ga-DOTA-SST) PET in the detection of... (Meta-Analysis)
Meta-Analysis
We performed a systematic review and metaanalysis of the performance of Ga-DOTA-conjugated somatostatin receptor-targeting peptide (Ga-DOTA-SST) PET in the detection of pheochromocytomas and paragangliomas (PPGLs). PubMed and Embase were searched until May 8, 2018. We included studies that reported the detection rate of Ga-DOTA-SST PET in patients with PPGLs. Detection rates were pooled using a random-effects model. Subgroup analyses and metaregression were performed to explore the cause of heterogeneity. Thirteen studies were included for qualitative synthesis. Per-lesion detection rates of Ga-DOTA-SST PET were consistently higher (ranging from 92% to 100%) than other imaging modalities, including F-fluorohydroxyphenylalanine (F-FDOPA) PET, F-FDG PET, and I-metaiodobenzylguanidine (I-MIBG) scintigraphy. However, in patients with polycythemia/paraganglioma syndrome, the detection rate of Ga-DOTA-DOTATATE PET was 35%. Nine studies (215 patients) with no specific inclusion criteria for subtype were quantitatively synthesized. The pooled detection rate was 93% (95% confidence interval [CI], 91%-95%), which was significantly higher than that of F-FDOPA PET (80% [95% CI, 69%-88%]), F-FDG PET (74% [95% CI, 46%-91%]), and I-MIBG scan (38% [95% CI, 20%-59%], < 0.001 for all). A greater prevalence of head and neck paragangliomas was associated with higher detection rates of Ga-DOTA-SST PET ( = 0.0002). Ga-DOTA-SST PET exhibited superior performance for lesion detection, over other functional imaging modalities, in patients with PPGLs, with the exception of polycythemia/paraganglioma syndrome. This might suggest Ga-DOTA-SST PET as a first-line imaging modality for the primary staging of PPGL or the restaging of PPGL with unknown genetic status.
Topics: Adrenal Gland Neoplasms; Gallium Radioisotopes; Heterocyclic Compounds, 1-Ring; Humans; Paraganglioma; Peptides; Pheochromocytoma; Receptors, Somatostatin
PubMed: 30030341
DOI: 10.2967/jnumed.118.211706 -
American Journal of Hematology May 2018Patients with a Ph-negative myeloproliferative neoplasm (MPN) may harbor or develop lymphoproliferative disorders (LPD), however, the clinical and molecular determinants...
Patients with a Ph-negative myeloproliferative neoplasm (MPN) may harbor or develop lymphoproliferative disorders (LPD), however, the clinical and molecular determinants of MPN and LPD co-occurrence are still uncertain. To systematically pool the available knowledge, we conducted a scoping review of literature published since January 2005 and analyzed single-patient clinical data from 50 papers reporting 214 individuals harboring both MPN and LPD. Patients had been diagnosed essential thrombocythemia (44%), polycythemia vera (29%), or myelofibrosis (23%) at a median age of 67 years (26-94): half of them incurred a LPD after a median of 72 months from MPN diagnosis, while in 20% the LPD diagnosis was antecedent or synchronous. Patients mainly incurred indolent LPD, particularly chronic lymphocytic leukemia (CLL), while aggressive lymphomas and multiple myeloma were a relevant portion of the LPDs occurring in the follow-up of MPN. CLL was preferentially diagnosed in PV patients and was associated with a very high male-to-female ratio, as well as an older age at MPN diagnosis. On converse, multiple myeloma was rarely reported in PV patients and was preferentially diagnosed in female patients not harboring the JAK2 V617F mutation. Based on the 46 cases reporting follow-up data, median survival after MPN diagnosis was 96 months. This thorough review of published evidence confirms that LPD are relevant clinical events in the history of MPN patients. Controlled studies are needed to better refine individuals at higher risk of developing LPD, to support surveillance programs and to avoid therapies possibly favoring LPD.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Janus Kinase 2; Lymphoproliferative Disorders; Male; Middle Aged; Myeloproliferative Disorders; Neoplasms; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 29377227
DOI: 10.1002/ajh.25049