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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 -
Seminars in Thrombosis and Hemostasis Mar 2024Venous and arterial thromboembolism are major complications of myeloproliferative neoplasms (MPNs), comprising polycythemia vera (PV), essential thrombocythemia (ET),...
Venous and arterial thromboembolism are major complications of myeloproliferative neoplasms (MPNs), comprising polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Global hemostasis assays, including thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), and thromboelastography (TEG), have been proposed as biomarkers to assess the hypercoagulability and thrombotic risk stratification in MPNs. We performed a systematic literature review on the parameters of TGA, ROTEM, and TEG and their association with thrombotic events and treatment strategies in MPNs. Thirty-two studies (all cross-sectional) were included, which collectively enrolled 1,062 controls and 1,608 MPN patients. Among the 13 studies that reported arterial or venous thrombosis, the overall thrombosis rate was 13.8% with 6 splanchnic thromboses reported. Out of the 27 TGA studies, there was substantial heterogeneity in plasma preparation and trigger reagents employed in laboratory assays. There was a trend toward increased peak height among all MPN cohorts versus controls and higher endogenous thrombin potential (ETP) between ET patients versus controls. There was an overall trend toward lower ETP between PV and PMF patients versus. controls. There were no substantial differences in ETP between JAK2-positive versus JAK2-negative MPNs, prior history versus negative history of thrombotic events, and among different treatment strategies. Of the three ROTEM studies, there was a trend toward higher maximum clot firmness and shorter clot formation times for all MPNs versus controls. The three TEG studies had mixed results. We conclude that the ability of parameters from global hemostasis assays to predict for hypercoagulability events in MPN patients is inconsistent and inconclusive. Further prospective longitudinal studies are needed to validate these biomarker tools so that thrombotic potential could be utilized as a primary endpoint of such studies.
Topics: Humans; Thrombin; Cross-Sectional Studies; Myeloproliferative Disorders; Polycythemia Vera; Thrombosis; Thrombocythemia, Essential; Hemostasis; Biomarkers; Thrombophilia; Janus Kinase 2
PubMed: 37068511
DOI: 10.1055/s-0043-57010 -
The Journal of Allergy and Clinical... 2018The idiopathic systemic capillary leak syndrome is a rare disease characterized by unexplained recurrent shock caused by capillary hyperpermeability. Because of the...
BACKGROUND
The idiopathic systemic capillary leak syndrome is a rare disease characterized by unexplained recurrent shock caused by capillary hyperpermeability. Because of the rarity of the disease, this disease has easily been misdiagnosed and evidence of efficacious agents used empirically is lacking.
OBJECTIVE
To analyze the clinical and laboratory data, treatment modalities, and mortality rate of patients and to find contributing factors leading to mortality.
METHODS
We searched MEDLINE (inception to December 2016) and reviewed reference lists of previous systematic reviews. A total of 133 case reports (161 patients) and 5 case series (102 patients) of idiopathic systemic capillary leak syndrome were included.
RESULTS
Patients had hypotension (81.4%), edema (64.6%), and previous flu-like illness (34.2%). This disease was misdiagnosed as hypovolemic shock, septic shock, polycythemia vera, or angioedema. Thirty-seven patients died (23%) mainly because of systemic capillary leak syndrome itself (78.4%). There were significant differences in the survival rates between patients who were treated with prophylactic β2 agonists, methylxanthines, and intravenous immunoglobulins and those who were not. The estimated 1-, 5-, and 10-year survival rate of patients treated with intravenous immunoglobulins was 100%, 94%, and 94%, respectively.
CONCLUSIONS
We systematically analyzed in detail clinical presentations of all reported patients and identified various factors associated with mortality and effects of prophylactic treatment in idiopathic systemic capillary leak syndrome. The findings of this review will facilitate diagnostic approaches of idiopathic systemic capillary leak syndrome and aid in the selection of treatment.
Topics: Capillary Leak Syndrome; Humans; Prognosis
PubMed: 28939140
DOI: 10.1016/j.jaip.2017.07.021 -
The Journal of Urology Jan 2022We sought to compare testosterone formulations and determine the degree that hematocrit increases vary by testosterone therapy formulation. As head-to-head trials are... (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
We sought to compare testosterone formulations and determine the degree that hematocrit increases vary by testosterone therapy formulation. As head-to-head trials are rare, network meta-analysis of the contemporary studies is the only way to compare hematocrit changes by testosterone type, including topical gels and patches, injectables (both short-acting and long-acting) and oral tablets.
MATERIALS AND METHODS
We conducted a thorough search of listed publications in Scopus®, PubMed®, Embase®, Cochrane CENTRAL, and ClinicalTrials.gov. A total of 29 placebo-controlled randomized trials (3,393 men) met inclusion criteria for analysis of mean hematocrit change after testosterone therapy. Randomized controlled trial data for the following formulations of testosterone were pooled via network meta-analysis: gel, patch, oral testosterone undecanoate, intramuscular testosterone undecanoate, and intramuscular testosterone enanthate/cypionate.
RESULTS
All types of testosterone therapies result in statistically significant increases in mean hematocrit when compared with placebo. Meta-analysis revealed all formulations, including gel (3.0%, 95% CI 1.8-4.3), oral testosterone undecanoate (4.3%, 0.7-8.0), patch (1.4%, 0.2-2.6), intramuscular testosterone enanthate/cypionate (4.0%, 2.9-5.1), and intramuscular testosterone undecanoate (1.6%, 0.3-3.0) result in statistically significant increases in mean hematocrit when compared with placebo. When comparing all formulations against one another, intramuscular testosterone cypionate/enanthate were associated with a significantly higher increase in mean hematocrit compared to patch, but no differences in hematocrit between other formulations were detected.
CONCLUSIONS
All types of testosterone are associated with increased hematocrit; however, the clinical concern of this increase remains questionable, warranting future studies. This is the first network meta-analysis to quantify mean hematocrit change and compare formulations, given the absence of head-to-head trials.
Topics: Bayes Theorem; Drug Administration Routes; Drug Compounding; Hematocrit; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Testosterone
PubMed: 34445892
DOI: 10.1097/JU.0000000000002188 -
Ultrasound in Obstetrics & Gynecology :... Nov 2021Monochorionic twins with twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) are at increased risk of neurodevelopmental... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Monochorionic twins with twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) are at increased risk of neurodevelopmental impairment (NDI). This meta-analysis aimed to identify the prevalence of and perinatal risk factors for NDI in TTTS survivors treated with FLP.
METHODS
We performed a search in PubMed, EMBASE, Scopus and Web of Science, from inception to 13 February 2021, for studies evaluating perinatal risk factors for NDI in children diagnosed prenatally with TTTS managed by FLP. Data on severity of TTTS at the time of diagnosis, defined according to the Quintero staging system, FLP-related complications and perinatal outcomes were compared between children with a history of TTTS treated with FLP with and those without NDI, which was defined as performance on a cognitive or developmental assessment tool ≥ 2 SD below the mean or a defined motor or sensory disability. A random-effects model was used to pool the mean differences or odds ratios (OR) with the corresponding 95% CIs. Heterogeneity was assessed using the I statistic.
RESULTS
Nine studies with a total of 1499 TTTS survivors were included. The overall incidence of NDI was 14.0% (95% CI, 9.0-18.0%). The occurrence of NDI in TTTS survivors was associated with later gestational age (GA) at FLP (mean difference, 0.94 weeks (95% CI, 0.50-1.38 weeks); P < 0.0001, I = 0%), earlier GA at delivery (mean difference, -1.44 weeks (95% CI, -2.28 to -0.61 weeks); P = 0.0007, I = 49%) and lower birth weight (mean difference, -343.26 g (95% CI, -470.59 to -215.92 g); P < 0.00001, I = 27%). Evaluation of different GA cut-offs showed that preterm birth before 32 weeks was associated with higher risk for NDI later in childhood (OR, 2.25 (95% CI, 1.02-4.94); P = 0.04, I = 35%). No statistically significant difference was found between cases with and those without NDI with respect to Quintero stage of TTTS, recipient or donor status, development of postlaser twin anemia-polycythemia sequence, recurrence of TTTS and incidence of small- for-gestational age or cotwin fetal demise.
CONCLUSIONS
TTTS survivors with later GA at the time of FLP, earlier GA at delivery and lower birth weight are at higher risk of developing NDI. No significant association was found between Quintero stage of TTTS and risk of NDI. Our findings may be helpful for parental counseling and highlight the need for future studies to understand better the risk factors for NDI in TTTS survivors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Diseases in Twins; Female; Fetofetal Transfusion; Fetoscopy; Gestational Age; Humans; Incidence; Laser Coagulation; Neurodevelopmental Disorders; Postoperative Complications; Pregnancy; Pregnancy, Twin; Premature Birth; Risk Factors; Twins
PubMed: 34097320
DOI: 10.1002/uog.23706 -
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 -
Journal of Clinical Medicine Jun 2020Twin anemia polycythemia sequence (TAPS) is a rare complication of monochorionic diamniotic (MCDA) twins. Middle cerebral artery peak systolic velocity (MCA-PSV)...
Twin anemia polycythemia sequence (TAPS) is a rare complication of monochorionic diamniotic (MCDA) twins. Middle cerebral artery peak systolic velocity (MCA-PSV) measurements are used to screen for TAPS while fetal or neonatal hemoglobin levels are required for definitive diagnosis. We sought to perform a systematic review of the efficacy of MCA-PSV in diagnosing TAPS. Search criteria were developed using relevant terms to query the Pubmed, Embase, and SCOPUS electronic databases. Publications reporting diagnostic characteristics of MCA-PSV measurements (i.e., sensitivity, specificity or receiver operator curves) were included. Each article was assessed for bias using the Quality Assessment of Diagnostic Accuracy Studies II (QUADAS II) tool. Results were assessed for uniformity to determine whether meta-analysis was feasible. Data were presented in tabular form. Among publications, five met the inclusion criteria. QUADAS II analysis revealed that four of the publications were highly likely to have bias in multiple areas. Meta-analysis was precluded by non-uniformity between definitions of TAPS by MCA-PSV and neonatal or fetal hemoglobin levels. High-quality prospective studies with consistent definitions and ultrasound surveillance protocols are still required to determine the efficacy of MCA-PSV in diagnosing TAPS. Other ultrasound findings (e.g., placenta echogenicity discordance) may augment Doppler studies.
PubMed: 32512796
DOI: 10.3390/jcm9061735 -
The World Journal of Men's Health Jul 2024Hydroxyurea (HU) is a cytoreductive agent used as standard treatment option for sickle cell anaemia/disease (SCD), essential thrombocythemia (ET), and polycythaemia vera...
PURPOSE
Hydroxyurea (HU) is a cytoreductive agent used as standard treatment option for sickle cell anaemia/disease (SCD), essential thrombocythemia (ET), and polycythaemia vera (PV). Despite its overall good safety profile, its use also in relatively young patients raises an interest on its potential impact on spermatogenesis. To perform a systematic review of all published articles investigating fertility in male patients affected by SCD, ET, and PV and treated with HU. Two paradigmatic case reports of patients affected by PV and ET, respectively, have been also reported.
MATERIALS AND METHODS
PubMed, EMBASE, and Cochrane databases were queried for all the published studies indexed up to November 15th, 2022. A combination of the following keywords was used: "hydroxyurea," "fertility," "male," "sperm," "sickle cell anaemia," "sickle cell disease," "essential thrombocythemia," "polycythaemia vera."
RESULTS
Of 48 articles identified, 8 studies, involving 161 patients, were eligible for inclusion. Overall, the number of spermatogonia per round cross section of seminiferous tubule were decreased in patients with SCD compared to healthy males. HU treatment was always associated with a worsening of semen parameters, even up to azoospermia. Notably, treatment discontinuation was associated with an improvement of semen parameters and a trend toward normalization in the case of PV and ET, with a less clear amelioration in men with SCD. In both our patients with either PV or ET, HU discontinuation was associated with a significant improvement of spermatogenesis with successful spontaneous pregnancies.
CONCLUSIONS
Published evidence do not consistently report normalization of spermatogenesis after HU discontinuation in SCD cases. Conversely, the literature almost consistently reported an improvement of semen parameters at the discontinuation of HU therapy in PV and ET cases. Our real-life two cases confirmed those findings. The willing of fatherhood and the need for effective fertility treatment warrant further research to improve work-up management in men with hematological disorders.
PubMed: 38164027
DOI: 10.5534/wjmh.230069 -
Value in Health : the Journal of the... Jul 2020We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies.
OBJECTIVES
We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies.
METHODS
The following databases were searched up to September 2018: MEDLINE, EMBASE, The Cochrane Library, and the EQ-5D publications database on the EuroQol website. Additional references were extracted from reviewed articles. Only studies presenting EQ-Index results were incorporated. In view of the heterogeneity across the included publications, we limited ourselves to a narrative synthesis of original HSUVs found.
RESULTS
Fifty-nine studies (described in 63 articles) met the inclusion criteria. Data from 21 635 respondents provided 796 HSUV estimates for hematologic malignancy patients. EQ-Index scores ranged from -0.025 to 0.980. The most represented area was multiple myeloma (4 studies, 11 112 patients, and 249 HSUVs). In clinical areas such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and mantle cell lymphoma, we described over 50 health utilities in each. In contrast, we identified only 13 HSUVs (based on 4 studies and the data of 166 patients) for Hodgkin lymphoma. Areas without EQ-5D-based health utilities comprised: polycythemia vera, primary myelofibrosis, essential thrombocythemia, mastocytosis, myeloid sarcoma, chronic myelomonocytic, eosinophilic leukemia, and neutrophilic leukemia.
CONCLUSIONS
There is a wide range of HSUVs available for hematologic cancer patients with different indications. The review provides a catalog of utility values for use in cost-effectiveness models for hematologic malignancies.
Topics: Cost-Benefit Analysis; Health Status; Hematologic Neoplasms; Humans; Models, Economic; Quality of Life; Surveys and Questionnaires
PubMed: 32762998
DOI: 10.1016/j.jval.2020.04.1825