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Medicine Apr 2024The demand for Janus Kinase-2 (JAK2) testing has been disproportionate to the low yield of positive results, which highlights the need for more discerning test...
The demand for Janus Kinase-2 (JAK2) testing has been disproportionate to the low yield of positive results, which highlights the need for more discerning test strategies. The aim of this study is to introduce an artificial intelligence application as a more rational approach for testing JAK2 mutations in cases of erythrocytosis. Test results were sourced from samples sent to a tertiary hospital's genetic laboratory between 2017 and 2023, meeting 2016 World Health Organization criteria for JAK2V617F mutation testing. The JAK2 Somatic Mutation Screening Kit was used for genetic testing. Machine learning models were trained and tested using Python programming language. Out of 458 cases, JAK2V617F mutation was identified in 13.3%. There were significant differences in complete blood count parameters between mutation carriers and non-carriers. Various models were trained with data, with the random forest (RF) model demonstrating superior precision, recall, F1-score, accuracy, and area under the receiver operating characteristic, all reaching 100%. Gradient boosting (GB) model also showed high scores. When compared with existing algorithms, the RF and GB models displayed superior performance. The RF and GB models outperformed other methods in accurately identifying and classifying erythrocytosis cases, offering potential reductions in unnecessary testing and costs.
Topics: Humans; Artificial Intelligence; Polycythemia; Machine Learning; Algorithms; Hemoglobins; Janus Kinase 2
PubMed: 38579024
DOI: 10.1097/MD.0000000000037751 -
Chronic Obstructive Pulmonary Diseases... May 2024The prevalence of iron deficiency in patients with chronic obstructive pulmonary disease (COPD) varies in previous studies. We aimed to assess its prevalence according...
BACKGROUND
The prevalence of iron deficiency in patients with chronic obstructive pulmonary disease (COPD) varies in previous studies. We aimed to assess its prevalence according to 3 well-known criteria for iron deficiency, its associations with clinical characteristics of COPD, and mortality.
METHODS
In a cohort study consisting of 84 COPD patients, of which 21 had chronic respiratory failure, and 59 were non-COPD controls, ferritin, transferrin saturation (TSat), and mortality across 6.5 years were assessed. Associations between clinical characteristics and iron deficiency were examined by logistic regression, while associations with mortality were assessed in mixed effects Cox regression analyses.
RESULTS
The prevalence of iron deficiency in the study population was 10%-43% according to diagnostic criteria, and was consistently higher in individuals with COPD, peaking at 71% in participants with chronic respiratory failure. Ferritin < cutoff was significantly associated with forced expiratory volume in 1 second (FEV) (odds ratio [OR] 0.33 per liter increase), smoking (OR 3.2), and cardiovascular disease (OR 4.7). TSat < 20% was associated with body mass index (BMI) (OR 1.1 per kg/m increase) and hemoglobin (OR 0.65 per g/dL increase). The combined criterion of low ferritin and TSat was only associated with FEV (OR 0.39 per liter increase). Mortality was not significantly associated with iron deficiency (hazard ratio [HR] 1.2-1.8).
CONCLUSION
The prevalence of iron deficiency in the study population increased with increasing severity of COPD. Iron deficiency, defined by ferritin < cutoff, was associated with bronchial obstruction, current smoking, and cardiovascular disease, while TSat < 20% was associated with reduced levels of hemoglobin and increased BMI. Iron deficiency was not associated with increased mortality.
PubMed: 38575374
DOI: 10.15326/jcopdf.2023.0477 -
Cancer Medicine Apr 2024Studies have shown that some single nucleotide polymorphisms (SNPs) could serve as excellent markers in foretelling the treatment outcome of interferon (IFN) in...
BACKGROUND
Studies have shown that some single nucleotide polymorphisms (SNPs) could serve as excellent markers in foretelling the treatment outcome of interferon (IFN) in myeloproliferative neoplasms (MPN). However, most work originated from western countries, and data from different ethnic populations have been lacking.
METHODS
To gain insights, targeted sequencing was performed to detect myeloid-associated mutations and SNPs in eight loci across three genes (IFNL4, IFN-γ, and inosine triphosphate pyrophosphatase [ITPA]) to explore their predictive roles in our cohort of 21 ropeginterferon alpha-2b (ROPEG)-treated MPN patients, among whom real-time quantitative PCR was also performed periodically to monitor the JAK2V617F allele burden in 19 JAK2V617F-mutated cases.
RESULTS
ELN response criteria were adopted to designate patients as good responders if they achieved complete hematological responses (CHR) within 1 year (CHR1) or attained major molecular responses (MMR), which occurred in 70% and 45% of the patients, respectively. IFNL4 and IFN-γ gene SNPs were infrequent in our population and were thus excluded from further analysis. Two ITPA SNPs rs6051702 A>C and rs1127354 C>A were associated with an inferior CHR1 rate and MMR rate, respectively. The former seemed to be linked to grade 2 or worse hepatotoxicity as well, although the comparison was of borderline significance only (50%, vs. 6.7% in those with common haplotype, p = 0.053). Twelve patients harbored 19 additional somatic mutations in 12 genes, but the trajectory of these mutations varied considerably and was not predictive of any response.
CONCLUSIONS
Overall, this study provided valuable information on the ethnics- and genetics-based algorithm in the treatment of MPN.
Topics: Humans; Neoplasms; Myeloproliferative Disorders; Treatment Outcome; Haplotypes; Germ Cells; Interferon Lambda; Interleukins
PubMed: 38572926
DOI: 10.1002/cam4.7166 -
Molecular Diagnosis & Therapy May 2024Erythrocytosis is attributed to various clinical and molecular factors. Many cases of JAK2-unmutated erythrocytosis remain undiagnosed. We investigated the...
INTRODUCTION
Erythrocytosis is attributed to various clinical and molecular factors. Many cases of JAK2-unmutated erythrocytosis remain undiagnosed. We investigated the characteristics and causes of JAK2-unmutated erythrocytosis.
METHODS
We assessed the clinical and laboratory results of patients with erythrocytosis without JAK2 mutations and performed targeted next-generation sequencing (NGS) panels for somatic and germline mutations.
RESULTS
In total, 117 patients with JAK2-unmutated erythrocytosis were included. The median hemoglobin and hematocrit levels were 17.9 g/dL and 53.4%, respectively. Erythropoietin levels were not below the reference range. Thrombotic events were reported in 17 patients (14.5%). Among JAK2-unmutated patients, 44 had undergone targeted panel sequencing consisting of myeloid neoplasm-related genes, and 16 had one or more reportable variants in ASXL1 (5/44), TET2, CALR, FLT3, and SH2B3 (2/44). Additional testing for germline causes revealed eight variants in seven genes in eight patients, including NF1, BPGM, EPAS1, PIEZO1, RHAG, SH2B3, and VHL genes. One NF1 pathogenic, one BPGM likely pathogenic, and six variants of undetermined significance were detected.
CONCLUSION
Somatic and germline mutations were identified in 36.4% and 33.3 % of the JAK2-unmutated group; most variants had unknown clinical significance. Not all genetic causes have been identified; comprehensive diagnostic approaches are crucial for identifying the cause of erythrocytosis.
Topics: Humans; Polycythemia; Janus Kinase 2; Female; Male; Middle Aged; Adult; High-Throughput Nucleotide Sequencing; Aged; Mutation; Germ-Line Mutation; Tertiary Care Centers; Young Adult; Aged, 80 and over; Adolescent; Genetic Predisposition to Disease
PubMed: 38568469
DOI: 10.1007/s40291-024-00703-3 -
Acta Medica Indonesiana Jan 2024Continuously holding its position as the sixth most common cause of cancer and the third leading cause of cancer death, globally, Hepatocellular Carcinoma (HCC) remains...
Continuously holding its position as the sixth most common cause of cancer and the third leading cause of cancer death, globally, Hepatocellular Carcinoma (HCC) remains as a healthcare priority. Production of various substances may result into systemic or metabolic complications, often known as paraneoplastic phenomena of HCC. A 56-year-old male with history of untreated chronic hepatitis B arrived with generalized weakness and intermittent headache in the last two days prior to admission. Laboratory findings demonstrated elevated hemoglobin (20.5 g/dl), alpha-fetoprotein (29,845 ng/dl), and d-Dimer (2,120 ng/ml) levels. Hypoglycemia (44 mg/dl) was documented with normal basal insulin level, confirming non-islet cell tumor hypoglycemia. Abdominal multiphasic CT-scan demonstrated a large solid lesion involving the whole right liver lobe, hyper-enhanced at arterial phase and wash-out pattern at venous and delayed phases, with portal vein thrombosis; thus, confirming HCC BCLC C. Further examinations revealed hypercellularity from bone marrow biopsy with the absence of JAK2 mutation. He underwent serial phlebotomy and received 80 mg acetylsalicylic acid orally, as well as cytoreductive agent to reduce the risk of thrombosis. Despite applications of different interventions, control of hypoglycemia could not be achieved without parenteral administration of high dextrose load. He was planned to receive oral multikinase inhibitor, however, he passed away due to severe hospital-acquired pneumonia. Paraneoplastic phenomena are common in HCC. Increased risk of blood hyper-viscosity and thrombosis attributed to polycythemia, as well as medical emergency resulting from hypoglycemia showed that both conditions should not be overlooked since they may worsen the patient's prognosis.
Topics: Male; Humans; Middle Aged; Carcinoma, Hepatocellular; Liver Neoplasms; Polycythemia; Thrombosis; Hypoglycemia
PubMed: 38561874
DOI: No ID Found -
Journal of Gastrointestinal and Liver... Mar 2024Polycythemia vera (PV) is one of the three BCR-ABL1-negative myeloproliferative neoplasms characterized by activating mutations in JAK2, which clinically presents as...
Polycythemia vera (PV) is one of the three BCR-ABL1-negative myeloproliferative neoplasms characterized by activating mutations in JAK2, which clinically presents as erythrocytosis and has an increased risk of both thromboembolic events and progression to myelofibrosis and acute myeloid leukemia. Splanchnic vein thrombosis is a rare manifestation of venous thromboembolism involving one or more abdominal vessels and is strongly associated with PV. We herein report a case in which hepatic infarction due to PV was saved by conservative treatment.
Topics: Humans; Polycythemia Vera; Hepatic Infarction; Primary Myelofibrosis; Venous Thrombosis
PubMed: 38554424
DOI: 10.15403/jgld-5379 -
Experimental Physiology Jun 2024Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive...
Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE-). Blood samples were collected from 30 EE+ and 15 EE- in La Rinconada (Peru, 5100-5300 m a.s.l.), with special attention given to the sampling pre-analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet-poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE- and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis.
Topics: Humans; Polycythemia; Blood Coagulation; Adult; Altitude; Thrombophilia; Male; Thrombelastography; Female; Hematocrit; Peru; Middle Aged; Altitude Sickness; Thrombin
PubMed: 38554124
DOI: 10.1113/EP091670 -
ESC Heart Failure Mar 2024To explore the potential interaction between use of SGLT2 inhibitors and the increase in haemoglobin in patients randomized to intravenous iron or the control group in...
AIMS
To explore the potential interaction between use of SGLT2 inhibitors and the increase in haemoglobin in patients randomized to intravenous iron or the control group in the IRONMAN (Effectiveness of Intravenous Iron Treatment versus Standard Care in Patients with Heart Failure and Iron Deficiency) trial.
METHODS AND RESULTS
This was a post hoc exploratory analysis of the IRONMAN trial which randomized patients with heart failure, a left ventricular ejection fraction (LVEF) ≤ 45% and iron deficiency (transferrin saturation <20% or ferritin <100 μg/L) to open label intravenous ferric derisomaltose or usual care. Of the 1137 randomized patients, 29 (2.6%) were taking an SGLT2 inhibitor at baseline. The mean (SD) change in haemoglobin from baseline at 4 weeks in those taking an SGLT2 inhibitor at baseline was 1.3 (1.2) g/dL in patients randomized to ferric derisomaltose and 0.1 (0.7) g/dL in the usual care group; between-group difference = 1.0 g/dL (95% CI 0.1, 1.8). The equivalent numbers in the no SGLT2 inhibitor group were 0.6 (0.9) g/dL in those randomized to ferric derisomaltose and 0.1 (0.8) g/dL in the usual care group; between-group difference = 0.4 g/dL (95% CI 0.3, 1.6); interaction P value = 0.10. No patient receiving an SGLT2 inhibitor at baseline developed polycythaemia during follow-up (defined as haemoglobin >16.5 g/dL [men] or >16 g/dL [women]).
CONCLUSIONS
In the IRONMAN trial, there was a trend to a greater increase in haemoglobin with ferric derisomaltose in iron-deficient patients taking an SGLT2 inhibitor at baseline, as compared with those not taking one.
PubMed: 38549192
DOI: 10.1002/ehf2.14742 -
Haematologica Mar 2024Not available.
Not available.
PubMed: 38546672
DOI: 10.3324/haematol.2023.284658 -
Journal of Clinical Medicine Mar 2024The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs)....
The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients after long term follow-up. Fourteen patients with MPN/LPN coexistence were diagnosed and treated according to guidelines at a single university center across two decades. The overall median age was 53 years (22-69). MPNs patients with subsequent LPNs had a shorter period of second malignancy development and a more aggressive course of LPN, which can cause fatal outcomes. Polycythemia vera and chronic lymphocytic leukemia were most commonly associated (36%). The mutation had 2/3 and cytogenetic abnormalities occurred in 1/3 of patients. MPN/LPN coexistence cases had significantly higher thrombotic potential (42.8%) and a higher third malignancy accruement frequency (21.4%) versus those without such malignancies. Considering the younger ages at MPN diagnosis, it is recommended to check regularly for blood lymphocytosis or lymphadenopathy occurrences and organomegaly progression faster than expected for MPN, with the aim of timely LPN diagnoses. The presence of molecular-cytogenetic abnormalities in a majority of patients indicate possible genetic instability and increased risk of development of multiple neoplasms, thus elevating thrombotic risk.
PubMed: 38542040
DOI: 10.3390/jcm13061816