-
Annals of Hematology Jun 2024Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies....
Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance.
PubMed: 38907072
DOI: 10.1007/s00277-024-05847-0 -
Leukemia & Lymphoma Jun 2024
PubMed: 38899619
DOI: 10.1080/10428194.2024.2368639 -
SAGE Open Medical Case Reports 2024Although disseminated cryptococcosis can occur occasionally, it is most commonly seen in immunodeficient patients. In 2005, a 43-year-old man was diagnosed with...
Although disseminated cryptococcosis can occur occasionally, it is most commonly seen in immunodeficient patients. In 2005, a 43-year-old man was diagnosed with polycythemia vera. Following in 2018, he experienced an unknown-cause fever and headache. To establish the source of the symptoms, a magnetic resonance imaging scan of the brain was performed, which indicated meningeal and gyral-leptomeningeal thickening and several localized T2 hyperintense lesions measuring up to 10 × 14 mm in diameter. was then cultivated from cerebrospinal fluid. Serum IgM antibodies against West Nile Virus were positive. After 8 weeks of treatment with amphotericin B and fluconazole, the overall condition improved, and the cerebrospinal fluid control culture became negative. The symptoms returned shortly after discontinuing antifungal therapy, necessitating the reintroduction of fluconazole. Currently, the patient is stable and responding positively to ruxolitinib. Here, it is demonstrated how a patient with polycythemia vera due to immunological weakness might develop disseminated cryptococcosis of the brain after West Nile virus infection.
PubMed: 38895656
DOI: 10.1177/2050313X241262145 -
Journal of Clinical Medicine Jun 2024Patients with myeloproliferative neoplasms (MPNs) experience a high disease-related symptom burden. A specific instrument to evaluate quality of life (QoL), i.e., the...
Translation, Cultural Adaptation, and Validation into Romanian of the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF TSS or MPN-10) Questionnaire.
Patients with myeloproliferative neoplasms (MPNs) experience a high disease-related symptom burden. A specific instrument to evaluate quality of life (QoL), i.e., the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; MPN-10), was developed. We conducted the translation, cultural adaptation, and validation into Romanian of the MPN-10. We translated the MPN-10 and tested its psychometric properties. We recruited 180 MPN patients: 66 polycythemia vera (36.67%), 61 essential thrombocythemia (33.89%), 51 primary and secondary myelofibrosis (SMF) (28.33%), and 2 MPN-unclassifiable (1.11%). The mean TSS was 19.51 ± 16.51 points. Fatigue, inactivity, and concentration problems were the most cumbersome symptoms. We detected scoring differences between MPN subtypes regarding weight loss ( < 0.001), fatigue ( = 0.006), early satiety ( = 0.007), night sweats ( = 0.047), pruritus ( = 0.05), and TSS ( = 0.021). There were strong positive associations between TSS and inactivity, fatigue, and concentration problems, and moderate negative correlations between QoL scores and all MPN-10 items. Cronbach's α internal consistency coefficient was 0.855. The Kaiser-Meyer-Olkin construct validity test result was 0.870 and the Bartlett Sphericity Test was significant ( < 0.001). Symptom scores were loaded into one single factor according to the exploratory factor analysis. The Romanian MPN-10 version displayed excellent psychometric properties and is a reliable instrument for assessing symptom burden and QoL in Romanian MPN patients.
PubMed: 38892995
DOI: 10.3390/jcm13113284 -
Fetal Diagnosis and Therapy Jun 2024Maternal laparotomy-assisted fetoscopic surgery for in-utero myelomeningocele repair has shown that a trans-amniotic membrane suture during fetoscopic port placement can...
Should we stitch-close the fetoscopic percutaneous access? A case-series of laparotomy to trans-amniotic membrane suturing for intrauterine port placement in fetoscopic surgery for twins.
INTRODUCTION
Maternal laparotomy-assisted fetoscopic surgery for in-utero myelomeningocele repair has shown that a trans-amniotic membrane suture during fetoscopic port placement can reduce postsurgical complications. Fetoscopic laser photocoagulation (FLP) for complex twins is typically performed percutaneously without a transmembrane stitch. However, in scenarios without a placental free window, maternal laparotomy may be used for recipient sac access. Here, we present the outcomes of our series of laparotomy-assisted FLP cases, including a trans-amniotic membrane suturing of the fetoscopic port.
METHODS
Retrospective series of twin-twin transfusion syndrome (TTTS) or twin anemia-polycythemia (TAPS) cases treated at 2 fetal centers that underwent maternal laparotomy to FLP from 9/2017 to 1/2023. We recorded preoperative and operative characteristics, as well as pregnancy and neonatal outcomes.
RESULTS
During the study period, 9 maternal laparotomy to FLP cases were performed. Two were excluded for prior percutaneous FLP in the pregnancy. The remaining seven utilized a maternal laparotomy to trans-amniotic membrane stitch with confirmation of proper suture placement under ultrasound guidance, and all surgeries were performed with a single 10 F Check-Flo® cannula via sharp. Mean gestational age (GA) at surgery was 19.1 weeks (range 16w4d-23w3d), with delivery occurring at a mean GA of 35.0 weeks (range 32w0d-37w1d), resulting in a mean latency of 15.8 weeks, significantly longer than what is reported in the literature and our own data (mean latency for percutaneous FLP 10.2, 95% CI 9.9-10.5). Furthermore, all cases underwent iatrogenic delivery before labor onset, with the only delivery prior to 34 weeks due to concern for post-laser TAPS.
CONCLUSION
This case series of laparotomy to FLP with trans-amniotic stitch, demonstrated no cases of spontaneous preterm birth and a longer-than-expected latency from surgery to delivery. Larger studies are warranted to investigate this approach.
PubMed: 38889699
DOI: 10.1159/000539894 -
Biological Cybernetics Jun 2024Silent hypoxemia, or "happy hypoxia," is a puzzling phenomenon in which patients who have contracted COVID-19 exhibit very low oxygen saturation ( < 80%) but do not...
Silent hypoxemia, or "happy hypoxia," is a puzzling phenomenon in which patients who have contracted COVID-19 exhibit very low oxygen saturation ( < 80%) but do not experience discomfort in breathing. The mechanism by which this blunted response to hypoxia occurs is unknown. We have previously shown that a computational model of the respiratory neural network (Diekman et al. in J Neurophysiol 118(4):2194-2215, 2017) can be used to test hypotheses focused on changes in chemosensory inputs to the central pattern generator (CPG). We hypothesize that altered chemosensory function at the level of the carotid bodies and/or the nucleus tractus solitarii are responsible for the blunted response to hypoxia. Here, we use our model to explore this hypothesis by altering the properties of the gain function representing oxygen sensing inputs to the CPG. We then vary other parameters in the model and show that oxygen carrying capacity is the most salient factor for producing silent hypoxemia. We call for clinicians to measure hematocrit as a clinical index of altered physiology in response to COVID-19 infection.
PubMed: 38884785
DOI: 10.1007/s00422-024-00989-w -
Acta Obstetricia Et Gynecologica... Jun 2024Twin-twin transfusion syndrome (TTTS) complicates approximately 10%-15% of all monochorionic twin pregnancies. The aim of this review was to evaluate the placental... (Review)
Review
Placental architectural characteristics following laser ablation within monochorionic twins complicated by twin-twin transfusion syndrome: A systematic review and meta-analysis of outcomes.
INTRODUCTION
Twin-twin transfusion syndrome (TTTS) complicates approximately 10%-15% of all monochorionic twin pregnancies. The aim of this review was to evaluate the placental architectural characteristics within TTTS twins following laser and elucidate their impact on fetal outcomes and operative success.
MATERIAL AND METHODS
Five databases were searched from inception to August 2023. Studies detailing post-delivery placental analysis within TTTS twins post-laser were included. Studies were categorized into two main groups: (1) residual anastomoses following laser and (2) abnormal cord insertion: either velamentous and/or marginal or proximate. The primary outcome was to determine the proportion of TTTS placentas with residual anastomoses and abnormal cord insertions post-laser. Secondary outcomes included assessing residual anastomoses on post-laser fetal outcomes and assessing the relationship between abnormal cord insertion and TTTS development. Study bias was critiqued using the Joanna Briggs Institute checklists and Cochrane risk of bias tool. Random-effects meta-analysis was used, and results were reported as pooled proportions or odds ratio (OR) with 95% confidence interval (CI). PROSPERO registration: CRD42023476875.
RESULTS
Twenty-six studies, comprising 4013 monochorionic twins, were included for analysis. The proportion of TTTS placentas with residual anastomoses following laser was 24% (95% CI, 0.12-0.41), with a mean and standard deviation of 4.03 ± 2.95 anastomoses per placenta. Post-laser residual anastomoses were significantly associated with intrauterine fetal death (OR, 2.38 [95% CI, 1.33-4.26]), neonatal death (OR, 3.37 [95% CI, 1.65-6.88]), recurrent TTTS (OR, 24.33 [95% CI, 6.64-89.12]), and twin anemia polycythemia sequence (OR, 13.54 [95% CI, 6.36-28.85]). Combined abnormal cord (velamentous and marginal), velamentous cord, and marginal cord insertions within one or both twins following laser were reported at rates of 49% (95% CI, 0.39-0.59), 27% (95% CI, 0.18-0.38), and 28% (95% CI, 0.21-0.36), respectively. Combined, velamentous and marginal cord insertions were not significantly associated with TTTS twins requiring laser (p = 0.72, p = 0.38, and p = 0.71, respectively) versus non-TTTS monochorionic twins.
CONCLUSIONS
To the best of our knowledge, this is the first review to conjointly explore outcomes of residual anastomoses and abnormal cord insertions within TTTS twins following laser. A large prospective study is necessitated to assess the relationship between abnormal cord insertion and residual anastomoses development post-laser.
PubMed: 38873725
DOI: 10.1111/aogs.14891 -
Leukemia & Lymphoma Jun 2024There has been remarkable progress in the development of novel therapeutic approaches for patients with polycythemia vera (PV). Historically, therapy goals in PV were to... (Review)
Review
There has been remarkable progress in the development of novel therapeutic approaches for patients with polycythemia vera (PV). Historically, therapy goals in PV were to mitigate thrombotic risks and control blood counts and symptoms. There is now increased focus on disease modification through progressive attrition of -mutant stem/progenitor cells. The approval of ropeginterferon, a novel monoPEGylated interferon, coupled with findings from LOW-PV and longer-term data from CONTINUATION-PV that strongly support a disease-modifying effect for interferon therapy, have transformed the treatment paradigm for this disorder. Results from MAJIC-PV demonstrate that disease modification can also be induced with JAK inhibitors, suggesting an urgent need to incorporate prospective molecular monitoring into PV trials. Novel agents, such as hepcidin mimetics, aim to help patients with PV restore normal hematocrit levels and become phlebotomy-free. In this review, we will summarize past, current and future approaches to PV management and highlight findings from key clinical studies.
PubMed: 38871488
DOI: 10.1080/10428194.2024.2361836 -
Clinical Laboratory Jun 2024Polycythemia is a common medical problem, frequently acquired and reactive to secondary conditions. High-altitude-associated hypoxia contributes to the greater...
BACKGROUND
Polycythemia is a common medical problem, frequently acquired and reactive to secondary conditions. High-altitude-associated hypoxia contributes to the greater prevalence of polycythemia at altitude. Primary clonal polycythemia vera (PV), even though it is rare, requires a different therapeutic approach. Suspicion of PV usually drives the diagnostic workup of polycythemia.
METHODS
In this retrospective lab record study, we collected all JAK2 tests requested over a three-year period. We analyzed requests that were made for the evaluation of polycythemia. Complete blood count (CBC) and imaging of the abdomen were collected.
RESULTS
Out of 208 total requests, 136 were for the purpose of polycythemia evaluation. JAK2 mutation was positive (confirming the presence of PV) in 22 (16.7%) cases. PV patients have the usual demographics reported elsewhere. Additionally, PV patients exhibit distinct hemogram results featuring leukocytosis, thrombocytosis, and hypochromic microcytic red blood cells (RBCs) related to the associated iron deficiency.
CONCLUSIONS
Many patients with polycythemia at altitude might be unnecessarily considered for an evaluation of PV, if hemoglobin/hematocrit is the sole deciding criterion. PV patients have a distinct CBC pattern that can be exploited to better select patients with polycythemia for further evaluation and thus reduce unnecessary workups.
Topics: Humans; Polycythemia Vera; Retrospective Studies; Altitude; Female; Male; Middle Aged; Janus Kinase 2; Adult; Blood Cell Count; Aged; Mutation; Polycythemia
PubMed: 38868887
DOI: 10.7754/Clin.Lab.2023.231150 -
British Journal of Haematology Jun 2024Myeloproliferative neoplasms (MPN) are characterized by a clonal proliferation of myeloid lineage cells within the bone marrow. The classical BCR-ABL negative MPNs are... (Review)
Review
Myeloproliferative neoplasms (MPN) are characterized by a clonal proliferation of myeloid lineage cells within the bone marrow. The classical BCR-ABL negative MPNs are comprised of polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. Historically, the majority of MPNs are diagnosed in adults older than 60 years of age; however, in recent years, there has been recognition of MPNs in the adolescent and young adult (AYA) population. AYAs with MPN, typically defined as between the ages of 15 and 39 years old, may comprise up to 20% of patients diagnosed with MPN. They demonstrate unique patterns of driver mutations and thrombotic events and remain at risk for progression to more aggressive disease states. Given the likely long length of time they will live with their disease, there is a significant unmet need in identifying well-tolerated and effective treatment options for these patients, particularly with the advent of disease modification. In this review, we provide a comprehensive overview of the clinical features, disease course and management of AYA patients with MPN and, in doing so, highlight key characteristics that distinguish them from their older counterparts.
PubMed: 38853641
DOI: 10.1111/bjh.19557