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Background/Objectives: The primary objective of this study was to investigate clinical manifestations, time to diagnosis, and number of biopsies in patients with extranodal natural killer T-cell lymphoma (ENKTL). The secondary objectives were to determine response rates, survival outcomes, prognostic factor for overall survival (OS), and validation of the Prognostic Index of Natural Killer Lymphoma (PINK), Ann Arbor staging system (AASS), and the CA system. Methods: This retrospective study included data pertaining to patients with newly diagnosed ENKTL in Chiang-Mai University Hospital from 2004 to 2020. Comparisons between the areas under the receiver operating characteristic curve (AUC) of prognostic models (PINK, AASS, and CA system) were made. Results: Sixty patients were enrolled (n = 60) with a mean age of 49.1 ± 13.4 years. The most frequent symptom of ENKTL was nasal obstruction (66%). The median time to diagnosis was 22 days (ranging from 3 to 84 days), with 36.7% requiring more than one biopsy for diagnosis. Most patients presented with limited stage disease (75%). The median OS was 49 months. Factors associated with increased mortality were advanced stage, bone marrow involvement, gastrointestinal tract involvement, and receiving chemotherapy. Following prognostic model validation, the CA system model scored the highest level of accuracy (AUC 0.61), followed by AASS (AUC 0.58) and PINK (AUC 0.54). Conclusions: Patients with ENKTL commonly presented with nasal obstruction, with 36.7% requiring more than one biopsy for diagnosis. An advanced stage, bone marrow involvement, or gastrointestinal tract involvement were associated with poor OS. The CA system model has the highest level of accuracy for prognostic determination.

BackgroundCerebral venous sinus thrombosis (CVST) is a rare type of thrombosis that affects the cerebral venous system. The data on neurological outcomes are limited.ObjectivesThis study aimed to investigate the neurological outcomes of CVST, contributing factors, clinical presentation, treatment and mortality.MethodsThis was a single-center, retrospective study at a university-based referral hospital in Thailand. Consecutive patients diagnosed with CVST between January 2010 and December 2020 were included. Outcomes were neurological outcomes measured by modified Rankin Scale (mRS), anticoagulant treatment, recurrence, and mortality.ResultsOne hundred and seven CVST patients were included with a mean age (± SD) of 42.7 ± 20.4 years. Following the treatment, neurological outcomes significantly improved, with the proportion of patients with mRS 0-1 increasing from 18.7% at diagnosis to 83.2% and 85.1% at three and six months, respectively (P < 0.001). Clinical variables were associated with residual neurological symptoms (mRS≥1) included age ≥ 50 years (OR 4.1, 95% CI; 1.7-9.4, P 0.001), male sex (OR 3.0, 95%CI; 1.4-6.6, P 0.006), the thrombus involvement in deep sinus system (OR 6.1, 95%CI; 1.1-76.9, P 0.04) and cerebral vein and dural sinus thrombosis (CVT) risk score ≥ 1 (OR 3.1, 95%CI; 1.3-7.5, P 0.014). Patients whose CVST was associated with hormonal therapy were found to have a lower risk of residual neurological symptoms (OR 0.2, 95%CI 0.1-0.6, P 0.004). Hormonal therapy was associated with anticoagulant discontinuation (OR 2.7, 95% CI 1.1-7.0; P = 0.04). The presence of malignancy increased the risk of bleeding (OR 5.8, 95% CI 1.4-24.1; P 0.016). Overall mortality was 2.8%. Of which 50% were related to major bleeding.ConclusionsA significant improvement in neurological outcomes was observed at 3 and 6 months after diagnosis. Older age, male sex, thrombus involvement in deep sinus system were associated with residual neurological symptoms.

AbstractBackground Thalassemia is the most prevalent hereditary anaemia worldwide. Severe forms of thalassemia can lead to reduced life expectancy due to disease-related complications.Objectives To investigate the survival of thalassemia patients across varying disease severity, causes of death and related clinical factors.Patients and methods We conducted a retrospective review of thalassemia patients who received medical care at Chiang Mai University Hospital. The analysis focused on survival outcomes, and potential associations between clinical factors and patient survival.Results A total of 789 patients were included in our study cohort. Among them, 38.1% had Hb H disease, 35.4% had Hb E/beta-thalassemia and 26.5% had beta-thalassemia major. Half of the patients (50.1%) required regular transfusions. Sixty-five patients (8.2%) had deceased. The predominant causes of mortality were infection-related (36.9%) and cardiac complications (27.7%). Transfusion-dependent thalassemia (TDT) (adjusted HR 3.68, 95% CI 1.39–9.72, p = 0.008) and a mean serum ferritin level ≥3000 ng/mL (adjusted HR 4.18, 95% CI 2.20–7.92, p

IntroductionElevated ambient pollution exposure is potentially linked to thromboembolism. However, the mechanisms by which particulate matter (PM) interferes with the balance of hemostatic system remain unclear. This study investigates PM-mediated hemostatic changes in individuals across unique seasonal variations of ambient pollution.MethodsThis prospective study was conducted between February and July 2020 during alterations in ambient pollution in Chiang Mai, Thailand. Blood tests from 30 healthy subjects were assessed at four-week intervals, four times in total. Various coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor (vWF), platelet count, and platelet functions, were evaluated. A mixed-effects model was used to analyze the impact of high PM2.5 and PM10 on hemostatic parameters.ResultsThirty male subjects with mean age of 38.9 ± 8.2 years, were included. High levels of PM2.5 and PM10 were significantly associated with PT shortening, with no such effect observed in aPTT. PM2.5 and PM10 values also positively correlated with vWF function, while vWF antigen levels remained unchanged. Soluble P-selectin showed a strong positive association with PM2.5 and PM10 levels. Platelet function analysis revealed no correlation with PM values.ConclusionShort-term exposure to elevated PM2.5 and PM10 concentrations was linked to shortened PT and enhanced vWF function in healthy individuals. Exploring the impact of these changes on clinically relevant thrombosis is crucial. Additional studies on the pathogenesis of pollution-related thrombosis are warranted for maintaining good health.

BackgroundA common complication of thalassemia is secondary osteoporosis. This study aimed to assess the prevalence and factors associated with low BMD in thalassemic patients.MethodThis is a cross-sectional study. Eligible patients were males aged within 18–49 years or premenopausal women diagnosed with thalassemia in Chiang Mai University Hospital between July 2021 and July 2022. The diagnosis of low BMD by dual-energy x-ray absorptiometry (DXA) was defined as a Z-score of -2.0 SD or lower in either the lumbar spine or femoral neck. Clinical factors associated with low BMD were analyzed using a logistic regression model.ResultsPrevalence of low BMD was 62.4% from 210 patients with a mean age of 29.7 ± 7.6 years. The predominant clinical characteristics of low BMD thalassemia patients were being female, transfusion-dependent (TDT) and a history of splenectomy. From multivariable analysis, the independent variables associated with low BMD were transfusion dependency (odds ratio, OR 2.36; 95%CI 1.28 to 4.38; p=0.006) and body mass index (BMI) (OR 0.71; 95%CI 0.61 to 0.82; p

There are limited data regarding the impact of disease-related complications on the survival of multiple myeloma (MM) patients. The primary objective of this study was to determine the prevalence of disease-related complications, including hypercalcemia, renal insufficiency, anemia, and bone lytic lesions in MM patients. The secondary objectives were to determine clinical characteristics, treatment outcomes, and the association of disease-related complications and mortality. A retrospective chart review of MM patients from November 2014 to December 2019 was conducted. A total of 200 MM patients were enrolled. The median age at diagnosis was 63 years. The bone lytic lesion was the most common disease-related complication found in 85% during first-line therapy, followed by anemia (71.5%), renal insufficiency (28.5%), and hypercalcemia (20%). While anemia was the most common complication during the second (51.2%) and third-line therapy (72%). The development of skeletal-related events (SREs) after treatment is a disease-related complication that is associated with decreased overall survival (HR 4.030, 95% CI 1.97–8.24, p < 0.001). The most common disease-related complication of MM at initial diagnosis is bone lytic lesions, whereas anemia is more common with subsequent relapses. The presence of SRE after treatment is associated with the increased mortality of MM patients.

Background/Objectives: Rivaroxaban and dabigatran are commonly used for thromboembolic disease management in active cancer patients. However, limited research explores the impact of concurrent chemotherapy on the pharmacodynamics of direct oral anticoagulants (DOAC). The aim of our study was to evaluate the impact of combined chemotherapy with rivaroxaban and dabigatran on the pharmacodynamics in patients with diffuse large B-cell lymphoma (DLBCL).; Methods: This was a prospective, pharmacodynamic study. Eligible subjects were ≥18 years old, diagnosed with DLBCL and initiating R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) immunochemotherapy. The enrolled adults received either rivaroxaban (10 mg once daily) or dabigatran etixalate (110 mg twice daily). Plasma anti-factor Xa (FXa) in participants on rivaroxaban and diluted thrombin time (dTT) in participants on dabigatran were assessed over the dosing interval before and after R-CHOP administration. Pharmacodynamic parameters of rivaroxaban and dabigatran were determined using a non-compartmental analysis.; Results: Twenty-six adults participated, with twelve in the rivaroxaban group and fourteen in the dabigatran group. The mean age was 59 ± 14.4 years. In the rivaroxaban group, the AUEC of FXa inhibition showed no significant change after R-CHOP (mean difference 3.8 ng·h/mL, 95% confidence interval (CI) −155.4 to 163.0, p = 0.96). Similarly, in the dabigatran group, the AUEC of dTT remained unchanged post R-CHOP (mean difference 54.41 ng·h/mL, 95% CI −99.09 to 207.9 ng/mL, p = 0.46). However, the median time-to-peak dTT was significantly faster with R-CHOP (3 h, [min–max, 1.5–8] compared to without it (4 h, [min–max, 3–8], p = 0.04); Conclusions: Concurrent R-CHOP chemotherapy did not significantly impact FXa inhibition by rivaroxaban or dTT by dabigatran. The time-to-peak dTT was faster when dabigatran was administered with R-CHOP.

IntroductionHyperuricemia is a common complication of hematologic malignancies, and hyperuricosuria in this population has shown conflicting results. This study aimed to determine the prevalence of hyperuricemia and parameters associated with serum uric acid (SUA) and urine uric acid (UUA) in patients with lymphoma and myeloproliferative neoplasms (MPN).MethodsThis cross-sectional study included adult patients with newly diagnosed lymphoma and MPN at the university-based hospital. Clinical characteristics were collected, and independent risk factors for hyperuricemia and hyperuricosuria were determined using multiple logistic regression.ResultsOne hundred and sixty-five patients were included with a median age of 55 years (45.5–64) and 51.5% were males. There were 91 patients (55.2%) with lymphoma and 74 cases (44.8%) of MPN. Overall, hyperuricemia was prevalent in 43.6% with a median SUA of 6.3 mg/dl (4.6–8) and hyperuricosuria was detected in 39.4% with a median 24-h UUA of 545 mg (365.4–991). Hyperuricemia was observed in patients with lymphoma and MPN in 20.9% and 71.6%, respectively, and hyperuricosuria in 15.4% and 68.9%, respectively. In lymphoma patients, estimated glomerular filtration rate (eGFR)

Abstract To date, evidence on optimal anticoagulant options in patients with AF who concurrently have active cancer remains elusive. To describe anticoagulant patterns and clinical outcomes among patients with a concomitant diagnosis of AF and cancer. Data were obtained from the University of Utah and Huntsman Cancer Institute (HCI) Hospitals. Patients were included if they had diagnosis of AF and cancer. Outcome was type and pattern of anticoagulant. Clinical outcomes were stroke, bleeding and all-cause mortality. From October 1999 to December 2020, there were 566 AF patients who concurrently had active cancer. Mean age ± standard deviation was 76.2 ± 10.7 and 57.6% were males. Comparing to warfarin, patients who received direct oral anticoagulant (DOACs) were associated with similar risk of stroke (adjusted hazard ratio, aHR 0.8, 95% confidence interval [CI] 0.2–2.7, P = 0.67). On contrary, those who received low-molecular-weight heparin (LMWH) were associated with significantly higher risk of stroke comparing to warfarin (aHR 2.4, 95% CI 1.0–5.6, P = 0.04). Comparing to warfarin, DOACs and LMWH was associated with similar risk of overall bleeding with aHR 1.1 (95% CI 0.7–1.6, P = 0.73) and aHR 1.1 (95% CI 0.6–1.7, P = 0.83), respectively. Patients who received LMWH but not DOACs were associated with increased risk of death as compared to warfarin, aHR 4.5 (95% CI 2.8–7.2, P

AbstractObjectives To compare the efficacy and side effects of salvage chemotherapy between etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) and ifosfamide, carboplatin and etoposide plus dexamethasone (DICE) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).Methods Medical records of patients with relapsed or refractory DLBCL receiving second-line ESHAP or DICE chemotherapy with or without rituximab from January 2007 to November 2022 were retrospectively reviewed. The primary objective was progression-free survival (PFS). The secondary objectives were overall survival (OS), overall response rate (ORR) and adverse events (AEs).Results Seventy patients were enrolled including 21 patients who received ESHAP and 49 patients who received the DICE regimen. Six patients (28.6%) and 19 patients (38.8%) in the ESHAP and DICE groups underwent ASCT, respectively. The ORR was 47.6% for ESHAP and 53.1% for DICE (p = .67). The two-year PFS was 14.3% for ESHAP and 26.5% for DICE (p = .33) with median PFS of 5 months and 14 months, respectively (hazard ratio 0.74; 95% CI 0.39–1.36, p = .330). The two-year OS was 14.3% for ESHAP and 26.5% for DICE (p = .37) with median OS of 8 months and 19 months, respectively. Patients in ESHAP group have more all-grade renal impairment than DICE group (23.8% vs. 6.1%, p = .047).Discussion and conclusions Efficacy between ESHAP and DICE regimens as salvage chemotherapy for relapsed or refractory DLBCL was not significantly different in terms of two-year PFS, two-year OS and ORR. DICE regimen had less renal AE than ESHAP.

Background Serotonin reuptake inhibitor (SRI) antidepressants are implicated in increasing the risk of bleeding among users; however, the comparative increase in bleeding risk with concurrent antithrombotic therapy (anticoagulant or antiplatelet) remains unclear. As such, we performed a systematic review and meta-analysis of all available evidence to evaluate the effects of SRI and the risk of bleeding complications among patients receiving antithrombotic therapy. Methods We searched Medline, Embase, PubMed, PsycINFO, Cochrane Library, Web of Science, Scopus, CINAHL, and grey literature (Google Scholar and preprint reports) up to 26 November, 2020, with no language restrictions (updated on 31 July 2021). The primary outcome of interest was major bleeding. Secondary outcomes included intracranial haemorrhage, gastrointestinal bleeding, and any bleeding events. We used a random-effects model meta-analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Results We did not identify any randomised studies but found 32 non-randomized studies (cohort or case–control) with 1,848,285 patients that fulfilled the study selection criteria and were included in the meta-analysis. Among individuals receiving anticoagulants (13 studies), SRI users experienced a statistically higher risk of major bleeding compared to non-SRI users: pooled OR was 1.39 (95% CI, 1.23–1.58; p

Introduction To determine the prevalence, clinical outcomes, and factors associated with hydroxyurea (HU) resistance or intolerance among polycythemia vera (PV) and essential thrombocythemia (ET) patients.Methods This study was a retrospective cohort study including PV and ET patients diagnosed by WHO criteria and treated with HU between January 2000 and June 2020. Clinical features, laboratory data, and resistance or intolerance of HU were collected. The prevalence, clinical outcomes, and associated factors of HU resistance or intolerance were analyzed.Results There were 260 patients including 144 ET and 116 PV. The prevalence of HU resistance or intolerance was 11.9% (31 patients) which was more frequent in ET patients (14.6% vs. 8.6% in PV). Patients who had HU resistance or intolerance significantly increased the risk of bleeding events (HR 2.64; 95% CI 1.19–5.85, P = 0.017). The risk factors of HU resistance or intolerance were low baseline hemoglobin levels (HR 0.90; 95%CI 0.84–0.97, P = 0.01), age more than 60 years old (HR 3.98; 95% CI 2.08–7.62, P

Background: The predisposing factors and clinical presentations of fungal foot infections caused by non-dermatophytes and dermatophytes are challenging to differentiate. Definite diagnoses of non-dermatophyte infections at first visits facilitate their treatment. Objectives: This study aimed to develop diagnostic criteria to differentiate fungal foot infections caused by Neoscytalidium dimidiatum and dermatophytes. Methods: Diagnostic prediction research based on a retrospective, observational, cross-sectional study. The reviewed patients were aged ≥18 and underwent a mycological examination for fungal foot infections. A fungal culture at the initial visit was the gold standard for determining causative organisms. Results: Analyses were carried out on the data from 371 patients. N. dimidiatum accounted for 184 (49.6%) infections, and dermatophytes caused the remaining 187 (50.4%) cases. Five significant predefined predictors were used to develop the diagnostic criteria and score. They were immunocompetence status, no family history of fungal infections, the absence of pruritus, the absence of other concurrent fungal skin infections, and agricultural work. The lower score cutoff was 11 (sensitivity 83.7% and specificity 57.8%). The score showed an area under the receiver operating characteristic curve of 0.755 and was well calibrated. Conclusions: The criteria and score show promise for clinical use, with acceptable discriminative performance and good calibration. They will help physicians differentiate the causative organisms in patients with fungal foot infections at the first visit, enabling the determination of appropriate antifungal treatment.

IntroductionThe optimal secondary thromboprophylactic strategies for patients with antiphospholipid syndrome (APS) and arterial thrombosis remain controversial. This study aimed to evaluate the comparative efficacy and safety of various antithrombotic strategies in APS with arterial thrombosis.MethodsA comprehensive literature search was conducted using OVID MEDLINE, EMBASE, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) from inception until 30 September 2022, with no language restrictions. The inclusion criteria for eligible studies were as follows: inclusion of APS patients with arterial thrombosis, treatment with either antiplatelet agents, warfarin, direct oral anticoagulants (DOACs), or a combination of these therapies, and reporting of recurrent thrombotic events.ResultsWe conducted a frequentist random-effects network meta-analysis (NMA) involving 13 studies with a total of 719 participants, comprising six randomized and seven non-randomized studies. In comparison to single antiplatelet therapy (SAPT), the combined use of antiplatelet and warfarin demonstrated a significant reduction in the risk of recurrent overall thrombosis, with a risk ratio (RR) of 0.41 (95% CI 0.20 to 0.85). Dual antiplatelet therapy (DAPT) showed a lower risk of recurrent arterial thrombosis compared to SAPT although the difference did not reach statistical significance, with an RR of 0.29 (95% CI 0.08 to 1.07). DOAC was associated with a significant increase in the risk of recurrent arterial thrombosis, with an RR of 4.06 (95% CI 1.33 to 12.40) when compared to SAPT. There was no significant difference in major bleeding among various antithrombotic strategies.DiscussionBased on this NMA, the combination of warfarin and antiplatelet therapy appears to be an effective approach in preventing recurrent overall thrombosis in APS patients with a history of arterial thrombosis. While DAPT may also show promise in preventing recurrent arterial thrombosis, further studies are needed to confirm its efficacy. Conversely, the use of DOACs was found to significantly increase the risk of recurrent arterial thrombosis.

Objectives: To evaluate the effect of metformin in improving platelet dysfu nction in women with gestational diabetes mellitus (GDM). Patients and methods: A randomized controlled trial was conducted on pregnant women diagnosed with GDM. Singleton low-risk pregnancies meeting the inclusion criteria were randomly allocated at 27–31 weeks to receive metformin and placebo through the rest of pregnancy. Thirty-seven and 39 cases were recruited into the metformin group and the placebo group, respectively. MPVs, P-selectin, and 8-isoprostane levels were determined at the time of allocation and 6 weeks after treatment. Obstetric and neonatal outcomes were also assessed. Results: Most baseline characteristics of the two groups were comparable. The levels of P-selectin after 6 weeks of treatment were significantly higher in the metformin group (68.9 ± 14.4 vs 60.6 ± 11.3; P-value = 0.006), indicating more platelet activation. All of the obstetric and neonatal outcomes were comparable except that birth weight was significantly lower in the metformin group (3018 ± 364 g vs 3204 ± 393 g; P-value = 0.037). Conclusion: Metformin, in addition to diet and lifestyle modifications, doe s not improve or worsen oxidative stress and platelet dysfunction in women with GDM. Nevertheless, metformin significantly reduces fetal weight in women with GDM, theoretically preventing macrosomia.

BackgroundWith adequate blood transfusion and iron chelation, thalassemia patients have a longer life expectancy and experience long-term metabolic complications, including osteoporosis, fractures, and bone pain. Alendronate, an oral bisphosphonate, is currently used to treat various types of osteoporosis. However, the efficacy for the treatment of thalassemia-associated osteoporosis remains unclear.MethodsWe conducted a randomized controlled trial to evaluate the efficacy of alendronate for the treatment of osteoporosis in thalassemia patients. Patients were included if they were males (18–50 years) or premenopausal females with low bone mineral density (BMD) (Z-score < -2.0 SD) or positive vertebral deformities from vertebral fracture analysis (VFA). Stratified randomization was performed according to sex and transfusion status. Patients were 1:1 allocated to receive once weekly alendronate 70 mg orally or placebo for a total duration of 12 months. BMD and VFA were re-evaluated at 12 months. Markers of bone resorption (C-terminal crosslinking telopeptide of type I collagen; CTX) and bone formation (Procollagen type I N-terminal propeptide; P1NP), and pain scores were measured at baseline, 6 months, and 12 months. The primary outcome was the change of BMD. The secondary endpoints were changes in bone turnover markers (BTM) and pain scores.ResultsA total of 51 patients received the study drug, 28 patients were assigned to receive alendronate and 23 patients to receive placebo. At 12 months, patients in the alendronate group had significant improvement of BMD at L1-L4 compared to their baseline (0.72 ± 0.11 vs 0.69 ± 0.11 g/cm2, p = 0.004), while there was no change in the placebo group (0.69 ± 0.09 vs 0.70 ± 0.06 g/cm2, p = 0.814). There was no significant change of BMD at femoral neck in both groups. Serum BTMs were significantly decreased among patients receiving alendronate at 6 and 12 months. The mean back pain score was significantly reduced compared to the baseline in both groups (p = 0.003). Side effects were rarely found and led to a discontinuation of the study drug in 1 patient (grade 3 fatigue).ConclusionAlendronate 70 mg orally once weekly for 12 months effectively improves BMD at L-spine, reduces serum BTMs, and alleviates back pain in thalassemia patients with osteoporosis. The treatment was well tolerated and had a good safety profile.

BackgroundDespite the conflicting data, the positivity of antiphospholipid antibodies (aPL) in cancer patients may be associated with an increased risk of thrombosis.ObjectiveTo identify the prevalence and impact of aPL on venous thromboembolic events (VTE) and arterial thrombosis (ATE) in ambulatory cancer patients.MethodsIn this single-center, prospective cohort study, we enrolled newly diagnosed ambulatory cancer patients receiving chemotherapy. Non-cancer controls were age- and sex-matched. Participants were evaluated for aPL. Primary outcomes were the composite outcome of VTE or ATE and the prevalence of aPL positivity in cancer patients. Secondary outcomes included the risk of VTE and ATE in cancer patients and all-cause mortality at six-month follow-up duration.ResultsThere were 137 cases and 137 controls with mean age of 56.0±12.3 and 55.5±12.1 years, respectively. Cancer patients were more likely to have positive aPL compared to controls, with the risk difference of 9.4% (95%CI 1.5 to 17.5). Composite of ATE or VTE occurred in 9 (6.6%) in cancer patients and 2 (1.5%) in controls. Cancer patients with aPL positivity were associated with higher risk of ATE or VTE (risk ratio [RR] 3.6, 95% CI 1.04-12.4). Positive LA in cancer patients were associated with higher risk of composites of ATE or VTE (RR 5.3 95%CI 1.3-21.0), whereas the anti-β2-GPI positivity were associated with increased risk of VTE (RR 4.7, 95%CI 1.1-19.2).ConclusionaPL was more prevalent in active cancer patients and positive aPL in cancer patients was associated with arterial or venous thrombosis.

IntroductionThis study aimed to evaluate the performance of the D-index, a calculated measure of neutropenic burden, in predicting the risk of invasive fungal infections (IFIs) in acute myeloid leukemia (AML) patients.MethodsA retrospective study of adult AML patients who received the first induction chemotherapy and developed febrile neutropenia was conducted. Clinical characteristics, laboratory data, and the calculation of the D-index and cumulative D-index (c-D-index) were collected and analyzed between patients with and without IFIs.ResultsA total of 101 patients were included, with 16 (15.8%) patients who developed IFIs. Clinical characteristics, antifungal prophylaxis, and AML cytogenetic risk were similar between patients with or without IFIs. The results showed that the D-index and c-D-index were more effective in predicting IFIs than the duration of neutropenia. With the D-index cutoff of 7083, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 81.3%, 83.5%, 48.2%, and 95.9%, respectively. c-D-index at 5625 revealed sensitivity, specificity, PPV, and NPV for IFIs of 68.8%, 68.2%, 28.9%, and 92.1%, respectively. Using this cutoff of c-D-index, patients without IFIs were overtreated with an antifungal regimen in 45 (52.9%) cases.ConclusionThe D-index and c-D-index were helpful indicators for defining the risk of IFIs in AML patients with febrile neutropenia.

Abstract Background Cardiorenal syndrome (CRS), a serious condition with high morbidity and mortality, is characterized by the coexistence of cardiac abnormality and renal dysfunction. There is limited information about CRS in association thalassemia. This study aimed to investigate the prevalence of CRS in thalassemia patients and also associated risk factors. Methods Thalassemia patients who attended the out-patient clinic of a tertiary care university hospital from October 2016 to September 2017 were enrolled onto this cross-sectional study. Clinical and laboratory findings from 2 consecutive visits, 3 months apart, were assessed. The criteria for diagnosis of CRS was based on a system proposed by Ronco and McCullough. Cardiac abnormalities are assessed by clinical presentation, establishment of acute or chronic heart failure using definitions from 2016 ESC guidelines or from structural abnormalities shown in an echocardiogram. Renal dysfunction was defined as chronic kidney disease according to the 2012 KDIGO guidelines. Results Out of 90 thalassemia patients, 25 (27.8%) had CRS. The multivariable analysis showed a significant association between CRS and extramedullary hematopoiesis (EMH) (odds ratio (OR) 20.55, p = 0.016); thalassemia type [β0/βE vs β0/β0 thalassemia (OR 0.005, p = 0.002)]; pulmonary hypertension (OR 178.1, p = 0.001); elevated serum NT-proBNP (OR 1.028, p = 0.022), and elevated 24-h urine magnesium (OR 1.913, p = 0.016). There was no association found between CRS and frequency of blood transfusion, serum ferritin, liver iron concentration, cardiac T2*, type of iron chelating agents, or urine neutrophil gelatinase-associated lipocalin level. Conclusions CRS is relatively common in thalassemia patients. Its occurrence is associated with laboratory parameters which are easily measured in clinical practice.

Abstract Background Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods This research aimed to study the leukocyte telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ≥18 years. Leukocyte telomere length was measured by real-time quantitative PCR. Results Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18–57) years, and mean pre-transfusion hemoglobin level was 7.1 (± 1.07) g/dL. The mean telomere to single copy gene (T/S) ratios of patients with TDT and the controls were 0.72 ± 0.18 and 0.99 ± 0.25, respectively (p

Anti-platelet factor 4 (anti-PF4) antibodies were identified as pathogenic antibodies for vaccine-induced immune thrombocytopenia and thrombosis (VITT) in subjects receiving ChAdOx1 nCoV-19 vaccinations. We performed a prospective cohort study to determine the prevalence of anti-PF4 and the effect of the ChAdOx1 nCoV-19 vaccine on anti-PF4 in healthy Thai subjects. Anti-PF4 antibodies were measured before and four weeks after receiving the first vaccination. Participants with detectable antibodies were scheduled for repeat anti-PF4 analysis at 12 weeks after the second vaccination. Of 396 participants, ten participants (2.53%; 95% confidence interval [CI], 1.22–4.59) were positive for anti-PF4 before receiving vaccinations. Twelve people (3.03%; 95% CI, 1.58–5.23) had detectable anti-PF4 after the first vaccination. There was no difference in the optical density (OD) values of anti-PF4 antibodies when comparisons were made between pre-vaccination and four weeks after the first vaccination (p = 0.0779). There was also no significant difference in OD values in participants with detectable antibodies. No subjects experienced thrombotic complications. Pain at the injection site was associated with an increased risk of being anti-PF4 positive at an odds ratio of 3.44 (95% CI, 1.06–11.18). To conclude, the prevalence of anti-PF4 was low in Thais and did not significantly change over time.

Background Intracranial hemorrhage (ICH) is the most devastating complication of recombinant tissue plasminogen activator (rtPA) treatment in acute ischemic stroke patients. Data on rtPA-associated asymptomatic ICH (aICH) are limited. Objectives To determine the incidence, risk factors, characteristics, management, and clinical outcome of rtPA-associated aICH. Methods The data were retrieved from the Chiang Mai University Hospital Stroke Registry between 1995 and 2019. Consecutive ischemic stroke patients were included if they were 18 or older and received rtPA. Study outcomes were the incidence and characteristics of aICH, management, 90-day modified Rankin scale (mRS), National Institute of Health Stroke Scale (NIHSS), Barthel index, and all-cause mortality. Results Of 725 rtPA treated patients, 166 (16.0%, 95% confidence interval [CI] 13.4–18.9) had aICH, 50 (6.9%, 95% CI 5.2–9.0) had symptomatic ICH (sICH). Patients with aICH had more hemorrhagic infarctions (HI) compared to sICH (81.9% vs 2.0%, P-value < 0.001). Fresh Frozen Plasma and cryoprecipitate were the most common blood products used to reverse the anticoagulant effect in sICH. Craniotomy was performed in 1% and 60% of patients who had aICH and sICH. At 90 days, patients who had aICH had poorer clinical outcomes (mRS, NIHSS and Barthel index) as compared to those without ICH. Compared to non-ICH patients, aICH patients were associated with increased risk of 90-day mortality, the hazard ratio (HR), 3.7, 95% CI 1.6–8.9. Conclusions The rtPA-associated aICH increased the risk of morbidity and mortality outcomes. Further treatment consensus, guideline generation, or clinical trials focusing on the treatment of rtPA-associated aICH may be required.

Background and Objectives: There is a lack of data regarding hormonal metabolic abnormalities resulting from the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone), a commonly used chemotherapy in diffuse large B-cell lymphoma (DLBCL). This study aimed to determine the incidence of hormonal and metabolic changes after R-CHOP therapy. Methods and Methods: This prospective cohort study initially included 17 DLBCL patients. Hormonal tests, including gonadal function, thyroid function, and ACTH stimulation tests for cortisol and metabolic markers, were performed before the 1st and after the 5th cycle of R-CHOP. The paired t-test was used to evaluate the changes. Statistical significance was set at p < 0.05. Results: Out of 17 patients, two died before the last follow-up, and 15 completed the study. LH levels were significantly higher in males after the 5th cycle (p = 0.04), while no significant changes were observed in other hormonal levels. After the 5th cycle, the only trend toward statistical significance was observed with higher FSH in males, higher blood glucose, and cholesterol. After the 5th cycle of chemotherapy, seven patients had at least one hormonal dysfunction, three patients had alterations in their thyroid function tests. Three patients had adrenal insufficiency (AI), one of whom also had secondary hypothyroidism concomitant with hypogonadism and AI. Additionally, two males had hypogonadism, and impaired fasting glucose was observed in three patients. Conclusions: Hormonal and metabolic abnormalities can occur in DLBCL after the 5th R-CHOP cycle. A high level of awareness and careful observation is of value in detecting these abnormalities, as some can be lethal.

The intestinal bacterial flora of febrile neutropenic patients has been found to be significantly diverse. However, there are few reports of alterations of in adult acute myeloid leukemia (AML) patients. Stool samples of each treatment-naïve AML patient were collected the day before initiation of induction chemotherapy (pretreatment), on the first date of neutropenic fever and first date of bone marrow recovery. Bacterial DNA was extracted from stool samples and bacterial 16s ribosomal RNA genes were sequenced by next-generation sequencing. Relative abundance, overall richness, Shannon's diversity index and Simpson's diversity index were calculated. No antimicrobial prophylaxis was in placed in all participants. Ten cases of AML patients (4 male and 6 female) were included with a median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes dominated during the period of neutropenic fever, subsequently declining after bone marrow recovery a pattern in contrast to that shown by Bacteroidetes and Proteobacteria. Enterococcus was more abundant in the febrile neutropenia period compared to pretreatment (mean difference +20.2; p < 0.0001) while Escherichia notably declined during the same period (mean difference -11.2; p = 0.0064). At the operational taxonomic unit (OTU) level, there was a significantly higher level of overall richness in the pretreatment period than in the febrile neutropenic episode (mean OTU of 203.1 vs. 131.7; p = 0.012). Both of the diversity indexes of Shannon and Simpson showed a significant decrease during the febrile neutropenic period. Adult AML patients with a first episode of febrile neutropenia after initial intensive chemotherapy demonstrated a significant decrease in gut microbiota diversity and the level of diversity remained constant despite recovery of bone marrow.

Lymphoma can present with either lymphadenopathy or extranodal involvement. There are limited clinicopathological data pertaining to the occurrence of primary extranodal lymphoma (pENL) in Thailand. This was a retrospective study conducted at Chiang-Mai University Hospital from 2012 to 2016. Patients 18 years of age and over and with a diagnosis of pENL were enrolled onto study. Data related to clinical presentations, histology, stage, treatment and response were collected. There were 104 pENL patients with a median age of 63 years included. The most common presentation was gastrointestinal symptoms (41%), followed by ear, nose, and throat symptoms (35%). Diffuse large B-cell lymphoma (DLBCL) was the most common morphological subtype (60%), followed by marginal zone lymphoma (15%). The majority of patients presented with stage II disease (55%). The five-year overall survival rate was 71%. The factors associated with mortality were hemoglobin

Background Inherited thrombophilias are well‐established predisposing factors for venous thromboembolism, but their role in arterial thrombosis, such as arterial ischemic stroke, remains uncertain. We aimed to evaluate the association between inherited thrombophilia (factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency) and risk of arterial ischemic stroke in adults. Methods and Results We searched PubMed, EMBASE, and Cochrane Library Databases from inception to December 31, 2018. We included case‐control or cohort studies of adults reporting the prevalence of inherited thrombophilias in those with arterial ischemic stroke and subjects without arterial ischemic stroke. Two reviewers (T.C., E.D.) independently searched the literature and extracted data. Pooled odds ratios (ORs) and 95% CIs were calculated using random‐effects model. We identified 68 eligible studies, which collectively enrolled 11 916 stroke patients and 96 057 controls. The number of studies reporting factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency were 56, 45, 15, 17, and 12, respectively. Compared with controls, patients with arterial ischemic stroke were significantly more likely to have the following inherited thrombophilias: factor V Leiden (OR, 1.25; 95% CI, 1.08–1.44; I2=0%), prothrombin G20210A mutation (OR, 1.48; 95% CI, 1.22–1.80; I2=0%), protein C deficiency (OR, 2.13; 95% CI, 1.16–3.90; I2=0%), and protein S deficiency (OR, 2.26; 95% CI, 1.34–3.80; I2=8.8%). Statistical significance was not reached for antithrombin deficiency (OR, 1.25; 95% CI, 0.58–2.67; I2=8.8%). Conclusions Inherited thrombophilias (factor V Leiden, prothrombin G20210A mutation, protein C deficiency, and protein S deficiency) are associated with an increased risk of arterial ischemic stroke in adults. The implications of these findings with respect to clinical management of patients with ischemic stroke require further investigation.

Establishment and analysis of mean platelet volume (MPV) may be helpful in the discrimination between underproduction or over-destruction of platelets as the causes of thrombocytopenia. The primary objective is to find the cut-off point of MPV for distinguishing causes of thrombocytopenia. The secondary objective is to validate the cut-off value of the MPV by using bone marrow examination. Thrombocytopenic patients were enrolled in a training set and a receiving operating characteristics (ROC) curve was plotted to obtain the cut-off value of MPV. A validation set of patients was recruited to validate the cut-off value. The training set included 240 patients. Half with with underproductive (n=120) and half with over-destructive thrombocytopenia (n=120). The best cut-off value of MPV was 8.8 fL. The validation set included 119 patients in total, again in 2 groups, those with underproductive (n=84) and those with overdestructive thrombocytopenia (n=35). The sensitivity, specificity, PPV and NPV when MPV ≥8.8 fL indicating over-destructive thrombocytopenia were 77%, 89%, 89% and 77%, respectively. MPV is useful for differentiating the cause of thrombocytopenia. The value of MPV ≥8.8 fL has acceptable sensitivity and specificity for diagnosis of over-destructive thrombocytopenia.

This study aims to find the cut-off value and diagnostic accuracy of the use of RDW as initial investigation in enabling the differentiation between IDA and NTDT patients. Patients with microcytic anemia were enrolled in the training set and used to plot a receiving operating characteristics (ROC) curve to obtain the cut-off value of RDW. A second set of patients were included in the validation set and used to analyze the diagnostic accuracy. We recruited 94 IDA and 64 NTDT patients into the training set. The area under the curve of the ROC in the training set was 0.803. The best cut-off value of RDW in the diagnosis of NTDT was 21.0% with a sensitivity and specificity of 81.3% and 55.3% respectively. In the validation set, there were 34 IDA and 58 NTDT patients using the cut-off value of >21.0% to validate. The sensitivity, specificity, positive predictive value and negative predictive value were 84.5%, 70.6%, 83.1% and 72.7% respectively. We can therefore conclude that RDW >21.0% is useful in differentiating between IDA and NTDT patients with high diagnostic accuracy

Background: There were some reports of peripheral artery occlusive disease (PAOD) associated with nilotinib usage in chronic myeloid leukemia (CML). These complications in other tyrosine kinase inhibitors are revealed as unknown. Materials and methods: We determined the prevalence of PAOD in patients with CML as compared with matched-control population by cross-sectional case-control study. Peripheral artery occlusive disease was screened by ankle-brachial index (ABI). Results: In total, 78 CML and 156 matched-control patients were included. The median age was 55 years. In all, 61 (78.2%) were on imatinib and 13 (16.7%) were on nilotinib, whereas 4 patients (5.2%) were on dasatinib. Prevalence of low ABI (

The aim of the present paper is to evaluate the efficacy and safety of colchicine and dapsone combination therapy in cases of steroid-dependent, relapsed and refractory immune thrombocytopenia (ITP). This is a retrospective study of ITP patients who attended the Hematology Clinic at Chiang Mai University Hospital (Thailand) from 1 January 2008 to 30 September 2014. Medical records and clinical data were reviewed for efficacy and adverse effects. Sixty-four ITP patients received the combination therapy. The median age was 46 years and 70.3% were female. The majority (65.6%) were relapsed ITP patients. Median platelet count before starting treatment was 22.6×109/L. The response rate was 82.8%, with 75.0% of patients having a complete response. Median time to response was 8 weeks. The response rate was higher in relapsed patients (90.4%) compared to refractory (61.5%) and steroid-dependent patients (77.8%). Steroid treatment was discontinued in 30 patients (50%) following combination therapy. The most common side effect was hemolysis due to dapsone which was found in eight patients (12.5%). We can therefore conclude that combination therapy with colchicine and dapsone is an alternative second-line therapy option in relapsed ITP cases with acceptable side effects.

Thrombosis is a major complication of polycythemia vera (PV) and also a well-known complication of thalassemia. We reported a case of non-atherosclerotic ST-segment elevation myocardial infarction (STEMI) in a 17- year-old man with concurrent post-splenectomized hemoglobin H-Constant Spring disease and JAK2 V617F mutation-positive PV. The patient initially presented with extreme thrombocytosis (platelet counts greater than 1,000,000/μL) and three months later developed an acute STEMI. Coronary artery angiography revealed an acute clot in the right coronary artery without atherosclerotic plaque. He was treated with plateletpheresis, hydroxyurea and antiplatelet agents. The platelet count decreased and his symptoms improved. This case represents the importance of early diagnosis, awareness of the increased risk for thrombotic complications, and early treatment of PV in patients who have underlying thalassemia with marked thrombocytosis.

Background. Nontransfusion dependent thalassemia (NTDT) is a milder form of thalassemia that does not require regular transfusion. It is associated with many complications, which differ from that found in transfusion-dependent thalassemia (TDT). Currently available information is mostly derived from beta-NTDT; consequently, more data is needed to describe complications found in the alpha-NTDT form of this disease. Methods. We retrospectively reviewed the medical records of NTDT patients from January 2012 to December 2013. Complications related to thalassemia were reviewed and compared. Results. One hundred patients included 60 females with a median age of 38 years. The majority (54 patients) had alpha-thalassemia. Overall, 83 patients had one or more complications. The three most common complications were cholelithiasis (35%), abnormal liver function (29%), and extramedullary hematopoiesis (EMH) (25%). EMH, cardiomyopathy, cholelithiasis, and pulmonary hypertension were more commonly seen in beta-thalassemia. Osteoporosis was the only complication that was more common in alpha-thalassemia. The risk factors significantly related to EMH were beta-thalassemia type and hemoglobin < 8 g/dL. The risk factors related to osteoporosis were female gender and age > 40 years. Iron overload (ferritin > 800 ng/mL) was the only risk factor for abnormal liver function. Conclusion. The prevalence of alpha-NTDT complications was lower and different from beta-thalassemia.

Objective: Rare disease Background: Thalassemia and hemoglobin (Hb) variants are the most common hereditary red blood cell disorders worldwide. Alpha-thalassemia and alpha-globin variants are caused by mutations of the alpha-globin genes (HBA2 and HBA1), resulting in impaired alpha-globin production and structurally abnormal globin, respectively. Clinical severity of alpha-thalassemia correlates with the number of affected alpha-globin genes, yielding a spectrum of clinical manifestations from mild to severe anemia. Routine diagnosis involves Hb analysis and PCR-based methods, yet identifying rare variants necessitates comprehensive clinical and hematologic laboratory data. The knowledge of phenotype and genotype correlation is useful for genetic counseling and treatment planning. Case Report: A 59-year-old Thai woman presented with chronic anemia. Her baseline Hb level ranged between 8.0 and 9.0 g/dL, with no history of transfusion. Physical examination showed mild pallor, without enlarged liver and spleen. Laboratory investigations showed microcytic, hypochromic anemia and abnormal Hb peak by Hb analysis (retention time 4.58 min by HPLC method). Common alpha-globin gene deletions, including the Southeast-Asian/Thai 3.7 kb and 4.2 kb deletions were tested using gap-PCR, with none of these deletions detected. Direct DNA sequencing revealed a compound heterozygosity of Hb Jax (HBA2: c.44G>C) and Hb Constant Spring (HBA2: c.427T>C). Conclusions: Compound heterozygosity of Hb Jax and Hb Constant Spring results in microcytic anemia. Hb Jax can be identified by Hb analysis, and diagnosis can be confirmed by direct DNA sequencing method. Coinheritance of Hb Jax and alpha-globin variants should be considered in cases with microcytic anemia and a specific Hb peak seen in Hb chromatogram. [ABSTRACT FROM AUTHOR]