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Cureus Mar 2024We conducted a retrospective observational cohort study between 2020 and 2023 in 26 patients with type 1 and type 2 diabetes mellitus (DM) who were using 3-4 injections...
The Discrepancy Between Hemoglobin A1c and Glucose Management Indicators in 26 Patients Treated With Continuous Glucose Monitoring in an Internal Medicine Residency Clinic.
We conducted a retrospective observational cohort study between 2020 and 2023 in 26 patients with type 1 and type 2 diabetes mellitus (DM) who were using 3-4 injections per day of insulin and were monitored by continuous glucose monitoring (CGM). The goal of this retrospective observational cohort study is to compare these two metrics in an internal medicine community primary care residency clinic. We used CGM devices, Dexcom G6 and G7, and Freestyle Libre 3. The goal was to compare the patient's hemoglobin A1c (HbA1c) taken during their clinic visit by phlebotomy as a marker for diabetic control with an estimated HbA1c glucose management indicator (GMI) derived from the 30-day CGM readings. HbA1c is derived from the blood, while the GMI value is derived from the interstitial fluid. Both parameters were taken within 30 days of each other. GMI was taken in the last 30 days. We excluded patients with known anemia, chronic kidney disease, polycythemia, cirrhosis of the liver, or metabolic dysfunction associated with steatohepatitis (MASH) because disease states can affect the measured HbA1c. Also, pregnant and African American patients were excluded. We concluded the measured HbA1c was 0.34% (4 mmol/mol) higher than the CGM-derived GMI. The relationship between factors that affect glycemic control was discussed in the article, as well as the future utilization of them in improving diabetic control and management. As the use of CGM continues to grow, addressing differences between laboratory-measured HbA1c and CGM-derived GMI is critical.
PubMed: 38650779
DOI: 10.7759/cureus.56768 -
Cytometry. Part B, Clinical Cytometry Apr 2024Thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), prefibrotic/early (pre-PMF), and overt fibrotic PMF (overt PMF) are classical...
Thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), prefibrotic/early (pre-PMF), and overt fibrotic PMF (overt PMF) are classical Philadelphia-Negative (Ph-negative) myeloproliferative neoplasms (MPNs). Differentiating between these types based on morphology and molecular markers is challenging. This study aims to clarify the application of flow cytometry in the diagnosis and differential diagnosis of classical MPNs. This study retrospectively analyzed the immunophenotypes, clinical characteristics, and laboratory findings of 211 Ph-negative MPN patients, including ET, PV, pre-PMF, overt PMF, and 47 controls. Compared to ET and PV, PMF differed in white blood cells, hemoglobin, blast cells in the peripheral blood, abnormal karyotype, and WT1 gene expression. PMF also differed from controls in CD34 cells, granulocyte phenotype, monocyte phenotype, percentage of plasma cells, and dendritic cells. Notably, the PMF group had a significantly lower plasma cell percentage compared with other groups. A lasso and random forest model select five variables (CD34CD19cells and CD34CD38 cells on CD34cells, CD13CD11b cells in granulocytes, CD38CD19plasma, and CD123HLA-DRbasophils), which identify PMF with a sensitivity and specificity of 90%. Simultaneously, a classification and regression tree model was constructed using the percentage of CD34CD38 on CD34 cells and platelet counts to distinguish between ET and pre-PMF, with accuracies of 94.3% and 83.9%, respectively. Flow immunophenotyping aids in diagnosing PMF and differentiating between ET and PV. It also helps distinguish pre-PMF from ET and guides treatment decisions.
PubMed: 38647185
DOI: 10.1002/cyto.b.22173 -
The Journal of Applied Laboratory... Apr 2024The most frequently ordered laboratory test worldwide is the complete blood count (CBC).
BACKGROUND
The most frequently ordered laboratory test worldwide is the complete blood count (CBC).
CONTENT
In this primer, the red blood cell test components of the CBC are introduced, followed by a discussion of the laboratory evaluation of anemia and polycythemia.
SUMMARY
As clinical chemists are increasingly tasked to direct laboratories outside of the traditional clinical chemistry sections such as hematology, expertise must be developed. This review article is a dedication to that effort.
PubMed: 38646908
DOI: 10.1093/jalm/jfae031 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Mar 2024To investigate the prevalence and influencing factors of isolated diastolic hypertension (IDH) in the Tibetan population in Tibet and to provide some evidence for the...
OBJECTIVE
To investigate the prevalence and influencing factors of isolated diastolic hypertension (IDH) in the Tibetan population in Tibet and to provide some evidence for the prevention and control of hypertension and other related diseases in high-altitude areas.
METHODS
A multistage stratified whole-group random sampling method was used to enroll participants from Ngari Prefecture, Nagqu City, Shannan City, and Lhasa City, Tibet. A total of 3918 native Tibetans with complete data were enrolled in the survey between June 2020 and August 2023. The participants were aged from 18 to 80. The demographic data, life habits, and chronic disease prevalence of the participants were collected. Fasting venous blood samples were collected to perform the routine blood tests and blood biochemistry tests. The prevalence of IDH in subgroups with different characteristics was analyzed and the influencing factors were analyzed by multivariate logistic regression, accordingly. The predictive value of influencing factors on the prevalence of IDH was analyzed by the receiver operating characteristic (ROC) curve and the findings were compared with those of the previous prediction models for IDH.
RESULTS
The prevalence of hypertension in the participants was 33.7% (=1321), among which, 395 had IDH, accounting for 29.9% of the hypertensive patients. The results of multivariate regression showed that age, heart rate, body mass index, waist circumference, hemoglobin, and low-density lipoprotein cholesterol were associated with risks of developing IDH (<0.05). The area under the ROC curve () was 0.71, which indicated improved accuracy for predicting the risks for IDH in comparison with previous predictive models for IDH. Among the influencing factors, BMI showed the best predictive value for IDH risks.
CONCLUSION
The prevalence of IDH is high among Tibetans in Tibet, suggesting the necessity for rational allocation of health resources in accordance. Compared with the previous IDH prediction models, the model proposed in this study is more suited for the Tibetan population. Targeted interventions should be carried out for the high-risk populations, such as young and middle-aged adults and populations suffering from overweight/obesity, central obesity, high-altitude polycythemia, and dyslipidemia, so as to effectively control the occurrence and development of IDH.
Topics: Humans; Tibet; Middle Aged; Prevalence; Hypertension; Adult; Male; Female; Aged; Risk Factors; Adolescent; Altitude; Young Adult; Aged, 80 and over; Body Mass Index
PubMed: 38645841
DOI: 10.12182/20240360501 -
Journal of Hematology Apr 2024Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved...
BACKGROUND
Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation.
METHODS
Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of allelic burden, time to first CHR, and safety assessments.
RESULTS
The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm at baseline to 50.2 cm at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed.
CONCLUSION
The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.
PubMed: 38644985
DOI: 10.14740/jh1245 -
CEN Case Reports Apr 2024A 66-year-old non-smoker presented with a 2-week history of new-onset pedal oedema and gross haematuria. On evaluation, he was found to be hypertensive and oedematous...
A 66-year-old non-smoker presented with a 2-week history of new-onset pedal oedema and gross haematuria. On evaluation, he was found to be hypertensive and oedematous with a haemoglobin of 19.1 g/dl, platelet count of 546,000/mm, and creatinine of 2.6 mg/dl. Urine examination revealed abundant RBCs with 3+ albumin on three separate occasions. His 24-h urine protein level was 3830 mg/day, with a serum cholesterol level of 303 mg/dl. Secondary erythrocytosis and thrombocytosis tests were negative. Bone marrow examination revealed hypercellularity, erythroid hyperplasia, tight clusters of large megakaryocytes, and megakaryocytic hyperplasia suggestive of polycythemia vera. PCR analysis revealed a JAK2V617 F (exon 14) mutation. In view of nephrotic syndrome, azotemia, and microscopic haematuria, a renal biopsy was performed, which revealed features of IgA nephropathy with advanced interstitial fibrosis and tubular atrophy. He was started on angiotensin receptor blockers with hydroxy urea as a part of treatment. This case report highlights the association of glomerular disease with polycythaemia vera and the need of prompt renal biopsy for diagnosis and management.
PubMed: 38643434
DOI: 10.1007/s13730-024-00879-x -
Prenatal Diagnosis Jul 2024Antenatal management of monochorionic pregnancies complicated by twin anemia polycythemia sequence (TAPS) remains sub-optimally defined. Our objective was to evaluate...
OBJECTIVES
Antenatal management of monochorionic pregnancies complicated by twin anemia polycythemia sequence (TAPS) remains sub-optimally defined. Our objective was to evaluate the safety and efficacy of fetoscopic selective laser photocoagulation with respect to fetal and neonatal survival.
METHODS
A case series is reported with patients referred to the Texas Children's Fetal Center for evaluation and management of suspected spontaneous TAPS without concomitant twin-to-twin syndrome from 2014 to 2023. All evaluations were performed by our team and patients with stage II-IV TAPS were offered expectant management, intrauterine transfusion, or laser therapy. Cases of post-laser TAPS were excluded from this study. Pregnancy and neonatal outcomes were obtained from electronic medical records.
RESULTS
During a 10-year time period, 18 patients presented to our center for the management of TAPS. Thirteen patients had stage II-IV TAPS (13/18, 72%) and elected to proceed with laser photocoagulation. All procedures were completed, and "solomonization" was performed for 12/13. Normalization of middle cerebral artery Dopplers in both fetuses was noted after all cases. There was one intrauterine fetal death of the 26 viable fetuses after laser treatment, which was complicated by selective growth restriction. Most patients (12/13) were delivered by Cesarean section at a mean gestational age of 29 ± 3 weeks. Subsequently, there was one ex-donor neonatal death in an infant who had prenatal hydrops. Overall, 30-day postnatal survival was 24/26 fetuses (92.3%).
CONCLUSIONS
In the setting of spontaneous TAPS, laser therapy is feasible and appears to be an effective approach with overall favorable perinatal outcomes.
Topics: Humans; Female; Pregnancy; Fetoscopy; Fetofetal Transfusion; Laser Coagulation; Adult; Infant, Newborn; Pregnancy Outcome; Polycythemia; Retrospective Studies; Pregnancy, Twin
PubMed: 38643401
DOI: 10.1002/pd.6576 -
Targeted Oncology May 2024Ruxolitinib (RUX), an orally administered selective Janus kinase 1/2 inhibitor, has received approval for the treatment of myelofibrosis, polycythemia vera, and...
BACKGROUND
Ruxolitinib (RUX), an orally administered selective Janus kinase 1/2 inhibitor, has received approval for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. We have previously demonstrated the anti-multiple myeloma effects of RUX alone and in combination with the immunomodulatory agent lenalidomide (LEN) and glucocorticosteroids both pre-clinically and clinically.
OBJECTIVE
This study aims to evaluate whether LEN can achieve clinical activity among patients with multiple myeloma progressing on the combination of RUX and methylprednisolone (MP).
METHODS
In this part of a phase I, multicenter, open-label study, we evaluated the safety and efficacy of RUX and MP for patients with multiple myeloma with progressive disease who had previously received a proteasome inhibitor, LEN, glucocorticosteroids, and at least three prior regimens; we also determined the safety and efficacy of adding LEN at the time of disease progression from the initial doublet treatment. Initially, all subjects received oral RUX 15 mg twice daily and oral MP 40 mg every other day. Those patients who developed progressive disease according to the International Myeloma Working Group criteria then received LEN 10 mg once daily on days 1-21 within a 28-day cycle in addition to RUX and MP, which were administered at the same doses these patients were receiving at the time progressive disease developed.
RESULTS
Twenty-nine subjects (median age 64 years; 18 [62%] male) were enrolled in this part of the study and initially received the two-drug combination of RUX and MP. The median number of prior therapies was six (range 3-12). The overall response rate from this two-drug combination was 31% and the clinical benefit rate was 34%. The best responses were 1 very good partial response, 8 partial responses, 1 minor response, 12 stable disease, and 7 progressive disease. The median progression-free survival was 3.5 months (range 0.5-36.2 months). The median time to response was 3.0 months. The median duration of response was 12.5 months (range 2.8-36.2 months). Twenty (69%) patients who showed progressive disease had LEN added to RUX and MP; all patients had prior exposure to LEN and all but one patient was refractory to their last LEN-containing regimen. After the addition of LEN, the overall response rate was 30% and the clinical benefit rate was 40%. The best responses of patients following the addition of LEN were 2 very good partial responses, 4 partial responses, 2 minor responses, 8 stable disease, and 4 progressive disease. The median time to response was 2.6 months (range 0.7-15.0 months). The median duration of response was not reached. The median progression-free survival following the addition of LEN was 3.5 months (range 0.3-25.9 months).
CONCLUSIONS
For patients with multiple myeloma, treatment with RUX and MP is effective and well tolerated, and LEN can be used to extend the benefit of this RUX-based treatment.
CLINICAL TRIAL REGISTRATION
This study is registered with ClinicalTrials.gov, NCT03110822, and is ongoing.
Topics: Humans; Multiple Myeloma; Male; Lenalidomide; Female; Aged; Pyrazoles; Nitriles; Pyrimidines; Middle Aged; Methylprednisolone; Antineoplastic Combined Chemotherapy Protocols; Aged, 80 and over; Disease Progression; Adult
PubMed: 38643346
DOI: 10.1007/s11523-024-01049-w -
ELife Apr 2024High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic...
High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen's ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.
Topics: Animals; Mice; Humans; Spleen; Altitude Sickness; Splenomegaly; Ferroptosis; Leukocytes, Mononuclear; Macrophages; Hypoxia
PubMed: 38629942
DOI: 10.7554/eLife.87496 -
American Journal of Hematology Jul 2024Polycythemia vera (PV) is a clonal disorder arising from the acquired somatic mutations of the JAK2 gene, including JAK2 or several others in exon 12. A 38-year-old...
Polycythemia vera (PV) is a clonal disorder arising from the acquired somatic mutations of the JAK2 gene, including JAK2 or several others in exon 12. A 38-year-old female had a stroke at age 32 and found to have elevated hemoglobin, normal leukocytes, normal platelets, and tested negative for JAK2 and exon 12 mutations. Next generation sequencing revealed a novel mutation: JAK2 in the pseudokinase domain (JH2) at 47.5%. Its presence in her nail DNA confirmed a germline origin. Her mother and her son similarly had erythrocytosis and a JAK2 mutation. Computer modeling indicated gain-of-function JAK2 activity. The propositus and her mother had polyclonal myelopoiesis, ruling out another somatic mutation-derived clonal hematopoiesis. Some erythroid progenitors of all three generations grew without erythropoietin, a hallmark of PV. The in vitro reporter assay confirmed increased activity of the JAK2 kinase. Similar to PV, the JAK2 native cells have increased STAT5 phosphorylation, augmented transcripts of prothrombotic and inflammatory genes, and decreased KLF2 transcripts. The propositus was not controlled by hydroxyurea, and JAK2 inhibitors were not tolerated; however, Ropeginterferon-alfa-2b (Ropeg-IFN-α) induced a remission. Ropeg-IFN-α treatment also reduced JAK2 activity in the propositus, her mother and JAK2 PV subjects. We report dominantly inherited erythrocytosis secondary to a novel germline JAK2 gain-of-function mutation with many but not all comparable molecular features to JAK2 PV. We also document a previously unreported inhibitory mechanism of JAK2 signaling by Ropeg-IFN-α.
Topics: Adult; Female; Humans; Gain of Function Mutation; Germ-Line Mutation; Interferon-alpha; Janus Kinase 2; Pedigree; Polycythemia; Polycythemia Vera
PubMed: 38629639
DOI: 10.1002/ajh.27311