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Revue Neurologique Apr 2017High altitude may be a factor associated with cerebral venous thrombosis (CVT). As our knowledge of CVT at high altitude is limited, it was decided to pool such... (Review)
Review
BACKGROUND AND OBJECTIVE
High altitude may be a factor associated with cerebral venous thrombosis (CVT). As our knowledge of CVT at high altitude is limited, it was decided to pool such information from the available case studies to determine whether high altitude can predispose to CVT.
METHODS
A systematic review of the literature was performed for cases reporting CVT at high altitude. Searches of the PubMed database (up to July 2016) were performed for publications, using 'cerebral venous thrombosis' and 'high altitude' as keywords. Cross-referencing was also done to complete the search.
RESULTS
Ultimately, 13 articles were included in our systematic review. The population consisted of 17 patients, predominately male (14/17), with a mean age of 32 (range: 19-47) years. Altitude range was 3000-8200m. Nine patients stayed at high altitude for>2 weeks; the duration of high altitude stay was unknown for the remainder. A hypercoagulable state was found in nine patients: secondary polycythemia in five; protein C deficiency in one; protein S deficiency in one; and factor V Leiden mutations in two. No comorbidities were found in any of these patients.
CONCLUSION
Long-term stays at high altitude in association with a hypercoagulable state - in particular, congenital or acquired thrombophilia - appears to predispose to CVT. The association of CVT with a single exposure to high altitude seems low, but the risk cannot as yet be specifically estimated.
Topics: Adult; Altitude; Blood Coagulation Disorders; Female; Humans; Intracranial Thrombosis; Male; Middle Aged; Neuroimaging; Venous Thrombosis; Young Adult
PubMed: 28038774
DOI: 10.1016/j.neurol.2016.11.004 -
Current Oncology (Toronto, Ont.) Mar 2024Neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) that usually results in poor clinical outcomes and may be accompanied by paraneoplastic... (Review)
Review
Neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) that usually results in poor clinical outcomes and may be accompanied by paraneoplastic syndromes (PNS). NEPC is becoming more frequent. It can initially manifest as PNS, complicating diagnosis. Therefore, we reviewed the literature on the different PNS associated with NEPC. We systematically reviewed English-language articles from January 2017 to September 2023, identifying 17 studies meeting PRISMA guidelines for NEPC and associated PNS. A total of 17 articles were included in the review. Among these, Cushing's Syndrome (CS) due to ectopic Adrenocorticotropic hormone (ACTH) secretion was the most commonly reported PNS. Other PNS included syndrome of inappropriate Anti-Diuretic Hormone secretion (SIADH), Anti-Hu-mediated chronic intestinal pseudo-obstruction (CIPO), limbic encephalitis, Evans Syndrome, hypercalcemia, dermatomyositis, and polycythemia. Many patients had a history of prostate adenocarcinoma treated with androgen deprivation therapy (ADT) before neuroendocrine features developed. The mean age was 65.5 years, with a maximum survival of 9 months post-diagnosis. NEPC is becoming an increasingly more common subtype of PCa that can result in various PNS. This makes the diagnosis and treatment of NEPC challenging. Further research is crucial to understanding these syndromes and developing standardized, targeted treatments to improve patient survival.
Topics: Male; Humans; Aged; Prostatic Neoplasms; Androgen Antagonists; Paraneoplastic Syndromes
PubMed: 38534956
DOI: 10.3390/curroncol31030123 -
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 -
Biomedicines Jan 2023The impact of primary arterial hypertension (HTN) in myeloproliferative neoplasms (MPNs) remains unclear, with scant literature available, mostly focusing on... (Review)
Review
The impact of primary arterial hypertension (HTN) in myeloproliferative neoplasms (MPNs) remains unclear, with scant literature available, mostly focusing on cardiovascular risk factors as a singular entity or on organ-specific HTN. Furthermore, available studies reporting findings on drug-induced HTN in MPNs report varying and contradictory findings. In consideration of the above, this study set out to systematically review the available literature and shed light on the occurrence of HTN in MPNs, its association with thrombosis, as well as the drugs used in MPN management that could increase blood pressure. The literature search yielded 598 potentially relevant records of which 315 remained after the duplicates ( = 283) were removed. After we screened the titles and the abstracts of these publications, we removed irrelevant papers ( = 228) and evaluated the full texts of 87 papers. Furthermore, 13 records did not meet the inclusion criteria and were excluded from the systematic review. Finally, a total of 74 manuscripts were entered into the qualitative synthesis and included in the present systematic review. Our systematic review highlights that HTN is the most common comorbidity encountered in MPNs, with an impact on both the occurrence of thrombosis and survival. Moreover, drug-induced HTN remains a challenge in the management of MPNs. Further research should investigate the characteristics of patients with MPNs and HTN, as well as clarify the contribution of HTN to the development of thrombotic complications, survival and management in MPNs. In addition, the relationship between clonal hematopoiesis of indeterminate potential, HTN, cardiovascular disease and MPNs requires examination in upcoming assessments.
PubMed: 36830925
DOI: 10.3390/biomedicines11020388 -
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 -
Life (Basel, Switzerland) Jul 2021Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid... (Review)
Review
Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells is noted. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are included in the category of Philadelphia-negative, so-called classical MPNs. The potential applications of liquid biopsy and liquid biopsy-based biomarkers have not been explored in MPNs until now. Thus, a systematic search was computed in PubMed/MEDLINE, Web of Science and The Cochrane Library and, in total, 198 potentially relevant papers were detected. Following the removal of duplicates ( = 85), 113 records were screened. After the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts ( = 81), we examined the full texts of 33 manuscripts. Finally, after we applied the exclusion and inclusion criteria, 27 original articles were included in this review. Overall, the data analyzed in this review point out that liquid biopsy and liquid biopsy-based biomarkers (cell-free DNA, extracellular vesicles, microparticles, circulating endothelial cells) could be used in MPNs for diagnostic and prognostic purposes. Future research is needed to clarify whether this technique can be employed to differentiate between MPN subtypes and secondary causes of erythrocytosis, thrombocytosis and myelofibrosis, as well as to predict the development of thrombosis.
PubMed: 34357048
DOI: 10.3390/life11070677 -
JAMA Network Open Oct 2019Myeloproliferative neoplasms (MPNs) are increasingly being identified in women of childbearing potential. Pregnancy in women with MPNs is associated with maternal... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Myeloproliferative neoplasms (MPNs) are increasingly being identified in women of childbearing potential. Pregnancy in women with MPNs is associated with maternal thrombosis, hemorrhage, and placental dysfunction leading to fetal growth restriction or loss.
OBJECTIVE
To evaluate the association between the use of aspirin, heparin, interferon, or combinations and live birth rate and adverse maternal outcomes in pregnant women with MPNs.
DATA SOURCES
Systematic searches of MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and the MEDLINE Epub Ahead of Print and In-Process and Other Non-Indexed Citations from inception to July 19, 2018, with no language restrictions, was conducted. Key search terms included myeloproliferative disorders, polycythemia vera, essential thrombocythemia, and primary myelofibrosis.
STUDY SELECTION
A study was eligible if it included pregnant patients with MPNs; interventions included aspirin, heparin, and/or interferon; there was a comparison group in which patients did not receive the intervention; the study reported on at least 1 of the study outcomes; and it was a randomized, case-control, or cohort study or series of at least 10 pregnancies. Data were extracted in duplicate; 0.5% of identified studies met selection criteria.
DATA EXTRACTION AND SYNTHESIS
The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and reported in accordance with Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data were pooled using the Mantel-Haenszel approach.
MAIN OUTCOMES AND MEASURES
Outcomes were the number of live births and maternal complications, specifically, arterial or venous thrombosis, hemorrhage, and preeclampsia.
RESULTS
Twenty-two studies reporting on 1210 pregnancies were included. The live birth rate was 71.3% (95% CI, 65.1%-77.6%). Use of aspirin (11 studies, 227 patients; unadjusted odds ratio, 8.6; 95% CI, 4.0-18.1) and interferon (6 studies, 90 patients; unadjusted odds ratio, 9.7; 95% CI, 2.3-41.0) were associated with higher odds of live birth. Addition of heparin to aspirin was not associated with higher odds of live birth (6 studies, 96 patients; unadjusted odds ratio, 2.1; 95% CI, 0.5-9.0). The most common adverse maternal event was preeclampsia, with an incidence of 3.1% (95% CI, 1.7%-4.5%).
CONCLUSIONS AND RELEVANCE
Most studies reported on pregnancy with essential thrombocythemia. Few studies reported on pregnancy with polycythemia vera and none with myelofibrosis met the inclusion criteria. Most studies were retrospective and early pregnancy losses may have been underreported. Moderate-quality evidence suggests that aspirin or interferon is associated with higher odds of live birth in pregnant women with MPN.
Topics: Antineoplastic Agents; Aspirin; Birth Rate; Female; Fibrinolytic Agents; Heparin; Humans; Interferons; Live Birth; Myeloproliferative Disorders; Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 31584685
DOI: 10.1001/jamanetworkopen.2019.12666 -
Blood Advances Jan 2020Ruxolitinib is a recommended second-line treatment for the prevention of thrombosis in patients with polycythemia vera who become resistant or intolerant to hydroxyurea;... (Meta-Analysis)
Meta-Analysis
Ruxolitinib is a recommended second-line treatment for the prevention of thrombosis in patients with polycythemia vera who become resistant or intolerant to hydroxyurea; however, evidence regarding its efficacy in terms of thrombosis reduction is uncertain. We searched Medline, Embase, and archives of abstracts from the European Hematology Association and the American Society of Hematology annual congresses from 2014 onward for randomized controlled trials comparing the treatment vs best available therapy (BAT). Our search retrieved 80 records; after screening of abstracts and full text, the total was reduced to 16. Evidence came from 4 randomized controlled trials, including 663 patients (1057 patients per year). We estimated a thrombosis risk ratio of 0.56 for ruxolitinib BAT, corresponding to an incidence of 3.09% and 5.51% patients per year, respectively. The number of thrombotic events reported with ruxolitinib was consistently lower than that with BAT in our sample, but, globally, the difference did not reach significance (P = .098). Hard evidence in favor of ruxolitinib is lacking; a clinical trial on selected patients at high risk of thrombosis would be warranted, but its feasibility is questionable.
Topics: Humans; Nitriles; Odds Ratio; Polycythemia Vera; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Thrombosis; Treatment Outcome
PubMed: 31985808
DOI: 10.1182/bloodadvances.2019001158 -
Frontiers in Oncology 2024Large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are...
BACKGROUND
Large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are uncertain and underreported.
MATERIALS AND METHODS
A systematic search was conducted in April 2022 through PubMed, Embase, and Cochrane. We reviewed cases of LCNEC developed either from or transformation from prostate adenocarcinoma and summarized the relevant pathophysiological course, treatment options, and outcomes.
RESULTS
A total of 25 patients with a mean age of 70.4 (range 43 87 years old) from 18 studies were included in this review. 13 patients were diagnosed with LCNEC of the prostate. 12 patients were from the transformation of adenocarcinoma post-hormonal therapy treatment. Upon initial diagnosis, patients diagnosed with prostatic LCNEC had a mean serum PSA value of 24.6 ng/ml (range: 0.09-170 ng/ml, median 5.5 ng/ml), while transformation cases were significantly lower at 3.3 ng/ml (range: 0-9.3 ng/ml, median 0.05 ng/ml). The pattern of metastasis closely resembles prostate adenocarcinoma. Six out of twenty-three cases displayed brain metastasis matching the correlation between neuroendocrine tumors and brain metastasis. Three notable paraneoplastic syndromes included Cushings syndrome, dermatomyositis, and polycythemia. Most patients with advanced metastatic disease received conventional platinum-based chemotherapy with a mean survival of 5 months. There was one exception in the transformation cohort with a somatic BRCA2 mutation who was treated with a combination of M6620 and platinum-based chemotherapy with an impressive PFS of 20 months. Patients with pure LCNEC phenotype have worse survival outcomes when compared to those with mixed LCNEC and adenocarcinoma phenotypes. It is unclear whether there is a survival benefit to administering ADT in pure pathologies.
CONCLUSION
LCNEC of the prostate is a rare disease that can occur or transformation from prostatic adenocarcinoma. Most patients present at an advanced stage with poor prognosis and are treated with conventional chemotherapy regimens. Patients who had better outcomes were those who were diagnosed at an early stage and received treatment with surgery or radiation and androgen deprivation therapy (ADT). There was one case with an exceptional outcome that included a treatment regimen of M6620 and chemotherapy.
PubMed: 38515575
DOI: 10.3389/fonc.2024.1341794 -
Cancer Imaging : the Official... Apr 2021Diagnostic and treatment response criteria for the JAK2/CALR/MPL mutation-related myeloproliferative neoplasms (MPNs) are largely based on bone marrow (BM) biopsy...
BACKGROUND
Diagnostic and treatment response criteria for the JAK2/CALR/MPL mutation-related myeloproliferative neoplasms (MPNs) are largely based on bone marrow (BM) biopsy results. However, these biopsies have several limitations, such as the risk of sampling error. Also, the prognostic impact of BM abnormalities is largely unclear. Although not currently used in clinical practice, imaging techniques might offer additional information. In this review, we investigated the value of BM, liver, and spleen imaging for diagnosis, prognostication, and response monitoring of the JAK2/CALR/MPL mutation-related MPNs (i.e. essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)).
METHODS
A systematic literature search was performed via PubMed, Embase and the Cochrane Library up to 2020 March 26th. Of 5505 identified records, 55 publications met the eligibility criteria (i.e. containing original data on the imaging appearance of BM, spleen, or liver in adult ET, PV, or MF patients, published in a peer-reviewed journal, written in English).
RESULTS
Many explorative studies described imaging features, sometimes with comparisons to clinical characteristics. Studies reporting measures of diagnostic accuracy included 1) splenic transient elastography to predict BM fibrosis grade in MF, 2) dynamic contrast-enhanced MRI to discern MF patients from ET patients and healthy controls, and 3) 18-fluorodeoxyglucose PET to detect residual disease after stem cell transplantation in MF. The diagnostic accuracies of radiography and Tc-colloid scintigraphy were derived from several other articles. Except for the study on 18-fluorodeoxyglucose PET, we established substantial concerns regarding risk of bias and applicability across these studies, using the QUADAS-2 tool. Three publications described a correlation between imaging results and prognosis, of which one quantified the effect.
CONCLUSIONS
Based on current data, MRI (T1-weighted/STIR, Dixon) seems especially promising for the evaluation of BM fat content - and indirectly cellularity/fibrosis - in MF, and possibly for estimating BM cellularity in ET/PV. 18-fluorodeoxyglucose and 18-fluorothymidine PET/CT might be useful for evaluating BM fibrosis, with good reported accuracy of the former for the diagnosis of residual disease. Further research on these and other techniques is warranted to determine their exact value. Future researchers should improve methodology and focus on evaluation of diagnostic accuracy and prognostic implications of results.
Topics: Adult; Bone Marrow; Female; Follow-Up Studies; Humans; Liver; Male; Myeloproliferative Disorders; Positron Emission Tomography Computed Tomography; Prognosis; Spleen
PubMed: 33879266
DOI: 10.1186/s40644-021-00405-7