Clinical characteristics and prognostic factors in intracranial hemorrhage patients with hematological diseases.

The clinical characteristics and prognosis of intracranial hemorrhage (ICH) in patients with hematological diseases remain controversial. This study aimed to describe the clinical characteristics and explore the prognostic factors in such patients. A total of 238 ICH patients with a hematological disease were recruited from the Institute of Hematology and Blood Diseases Hospital, China, from January 2015 to April 2020. The Cox proportional hazards model was used to identify the prognostic factors for 30-day mortality in ICH patients with a hematological disease. There were 123 cases of acute leukemia (AL), 20 of myelodysplasia/myeloproliferative neoplasm, 35 of aplastic anemia (AA), 29 of immune thrombocytopenia (ITP), 19 of congenital/acquired coagulation factor deficiency, and 12 of other hematological diseases. Furthermore, 121 patients presented with a multi-site hemorrhage (MSH), 58 with a single-site hemorrhage in the brain parenchyma (PCH), 23 with a subarachnoid hemorrhage, 33 with a subdural hemorrhage (SH), and three with an epidural hemorrhage. The Cox proportional hazards model indicated association of SH (vs PCH, hazard ratio [HR]: 0.230; 95% confidence interval [CI]: 0.053-0.996; P = 0.049), low white blood cells (≤ 100 × 109/L vs > 100 × 109/L, HR: 0.56; 95% CI: 0.348-0.910; P = 0.019), AA (vs AL, HR: 0.408; 95% CI: 0.203-0.821; P = 0.012), and ITP (vs AL, HR: 0.197; 95% CI: 0.061-0.640; P = 0.007) with improved 30-day mortality. However, increased age (HR: 1.012; 95% CI: 1.001-1.022; P = 0.034), MSH (vs PCH, HR: 1.891; 95% CI: 1.147-3.117; P = 0.012), and a disturbance of consciousness (HR: 1.989; 95% CI: 1.269-3.117; P = 0.003) were associated with increased risk of 30-day mortality. In conclusion, in this study, we revealed the clinical characteristics of Chinese ICH patients with a hematological disease. Moreover, we identified risk factors (age, white blood cells, AA, ITP, SH, MSH, and a disturbance of consciousness) that may influence 30-day mortality.

ABTS as an Electron Shuttle to Enhance the Oxidation Kinetics of Substituted Phenols by Aqueous Permanganate.

In this study, it was, interestingly, found that 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonate (ABTS), a widely used electron shuttle, could greatly accelerate the oxidation of substituted phenols by potassium permanganate (Mn(VII)) in aqueous solutions at pH 5-9. This was attributed to the fact that these substituted phenols could be readily oxidized by the stable radical cation (ABTS(•+)), which was quickly produced from the oxidation of ABTS by Mn(VII). The reaction of Mn(VII) with ABTS exhibited second-order kinetics, with stoichiometries of ∼5:1 at pH 5-6 and ∼3:1 at pH 7-9, and the rate constants varied negligibly from pH 5 to 9 (k = (9.44 ± 0.21) × 10(4) M(-1) s(-1)). Comparatively, the reaction of ABTS(•+) with phenol showed biphasic kinetics. The second-order rate constants for the reactions of ABTS(•+) with substituted phenols obtained in the initial phase were strongly affected by pH, and they were several orders of magnitude higher than those for the reactions of Mn(VII) with substituted phenols at each pH. Good Hammett-type correlations were found for the reactions of ABTS(•+) with undissociated (log(k) = 2.82-4.31σ) and dissociated phenols (log(k) = 7.29-5.90σ). The stoichiometries of (2.2 ± 0.06):1 (ABTS(•+) in excess) and (1.38 ± 0.18):1 (phenol in excess) were achieved in the reaction of ABTS(•+) with phenol, but they exhibited no pH dependency.

Association between Serum Lactate Dehydrogenase Level and 30-day Mortality in Patients with Intracranial Hemorrhage with Acute Leukemia in the Induction Phase: A Cohort Study.

Objectives This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. Methods This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted. Results We selected 91 patients diagnosed with acute leukemia and ICH. The overall 30-day mortality rate was 61.5%, with 56 of the 91 patients succumbing. Among those with LDH levels ≥ 570 U/L, the mortality rate was 74.4% (32 out of 43), which was higher than the 50% mortality rate of the LDH < 570 U/L group (24 out of 48) ( p = 0.017). In our multivariate regression models, the hazard ratios and their corresponding 95% confidence intervals for Log2 and twice the upper limit of normal LDH were 1.27 (1.01, 1.58) and 2.2 (1.05, 4.58), respectively. Interaction analysis revealed no significant interactive effect on the relationship between LDH levels and 30-day mortality. Conclusions Serum LDH level was associated with 30-day mortality, especially in patients with LDH ≥ 570 U/L.

[Comparison of Carbon Emissions in Different Treatment and Disposal Process Routes of Municipal Sludge].

With the introduction of the goal of carbon neutrality, the efficient resource recycling of municipal sludge has been given increasing attention. In order to scientifically evaluate the routes of sludge treatment and disposal from the perspective of carbon emissions, four typical routes were chosen for accounting the carbon emissions per ton for dry sludge (DS). Based on the Intergovernmental Panel on Climate Change (IPCC), combined with Chinese sludge characteristics, carbon emissions were divided into three types:the direct emissions, indirect emissions, and carbon offsets, and accounting boundaries were initiated at sludge thickening and ended at products or energies. The results showed that the total carbon emission of R4 (gravity thickening+thermal hydrolysis+anaerobic digestion+plate and frame filter pressing+transportation+land utilization) was 99.41 kg·t-1(calculated as CO2/DS, same below), which was the route with lowest carbon emissions. If the fugitive emission of CH4 from anaerobic digestion was avoided, the route (R4) could achieve carbon neutrality at this stage. Process units with larger carbon emissions should focus on optimization to reduce the carbon emissions, such as through thermal drying (1049.24 kg·t-1), deep dewatering (960.99 kg·t-1), sanitary landfill (786.24 kg·t-1), incineration (635.52 kg·t-1), aerobic composting (614.17 kg·t-1), and thermal hydrolysis (544.67 kg·t-1). The main carbon offsets were the incineration power generation (-1440.29 kg·t-1), CH4 collection of anaerobic digestion (-435.06 kg·t-1), land utilization (-415.83 kg·t-1), and building materials utilization (-169.75 kg·t-1). In summary, "anaerobic digestion and land utilization" has a great potential for carbon offsets, which should be advocated for as the widely used treatment.

Photoinduced remote regioselective radical alkynylation of unactivated C-H bonds.

A method for the remote regioselective alkynylation of unactivated C(sp3)-H bonds in diverse aliphatic amides by photogenerated amidyl radicals has been developed. The site-selectivity is dominated via a 1,5-hydrogen atom transfer (HAT) process of the amide. Mild reaction conditions and high regioselectivity are demonstrated in this methodology.

Kinetics and pathways of Bezafibrate degradation in UV/chlorine process.

UV/chlorine, as a novel disinfection method, has attracted great interest due to its effective removal for pathogenic microorganism and degradation of trace organic contaminants existed in water environment. This paper investigated the degradation kinetics and pathways of Bezafibrate (BZF), a typical antilipemic drug, during UV/chlorine process. The results showed that 92.3% of BZF was degraded after 20 min in UV/chlorine process. This indicated HO• and reactive chlorine species (RCSs) formed in UV/chlorine played the dominant role in degrading BZF. Observed rate constants of BZF degradation (k obs,BZF) in UV/chlorine process increased linearly in a wide chlorine dosage from 0.1 to 1.0 mM, which implied that ClO• generated from the reactions of chlorine with HO• and Cl• could react with BZF rapidly. The steady-state kinetic modeling result proved this deduction and the rate constant of ClO• with BZF was fitted to be 5.0 × 108 M-1 s-1. k obs,BZF was affected by Cl- and HA. The total contribution of RCSs (including Cl•, Cl2•-, and ClO•) to the degradation of BZF was determined to be ~ 80%, which is much higher than that of HO•. Thirteen degradation products of BZF were identified by LC-MS/MS. Initial degradation products were arisen from hydroxylation, chlorine substitution and cyclization by HO• and RCSs, and then further oxidized to generate acylamino cleavage and demethylation products.

[Relationship between the expression of autoantibodies against platelet membrane glycoprotein and therapeutic effect in primary immune thrombocytopenia].

OBJECTIVE: To study the expression of specific anti- platelet glycoprotein autoantibodies GP II b/III a, GP I b/IX and GP I a/II a in primary immune thrombocytopenia (ITP), and to evaluate the relationship between the therapeutic effect and the expression of specific anti- platelet glycoprotein antibodies GPIIb/IIIa, GPIb/IX and GPIa/IIa. METHODS: Anti-GPIIb/IIIa, GPIb/ IX and GP I a/II a antibodies were assayed by ELISA for patients with ITP. Total 442 patients in our hospital, who were retrospectively investigated from December 2010 to November 2012, were divided into newly diagnosed ITP, persistent and chronic ITP. The expression of specific anti- platelet glycoprotein antibody in each group was measured separately. The newly diagnosed ITP patients were treated with intravenous IgG (IVIG) and corticosteroids. The relationship between the expression of specific anti- platelet glycoprotein antibodies GPIIb/IIIa, GPIb/IX and GPIa/IIa and the complete response (CR) was studied. RESULTS: Positive rates of anti- platelet glycoprotein antibodies were 59.09%, 26.97% and 37.35% respectively in newly diagnosed ITP, persistent and chronic ITP, the difference was statistical significant (P<0.05). In newly diagnosed ITP, positive rate of antibody against GPIIb/IIIa was 38.64%, double positive rate of antibodies against both GP II b/III a and GP I a/II a was 15.91%, there was statistical significance (P<0.05) compared with that of persistent and chronic ITP. The complete response (CR) rate in newly diagnosed ITP patients with positive antibody against GP II b/III a was 80.39% after treatment with IVIG and corticosteroids. There was statistical significance compared with that in patients having no antibodies (P<0.05). CONCLUSION: The expression of antibodies against GP II b/III a and double positive for both GP II b/III a and GP I a/II a autoantibodies increased in newly diagnosed ITP patients. Patients with anti-GP II b/III a autoantibody had good response to medication with IVIG and corticosteroids.

[Acquired factor V inhibitor: 3 cases report and literature review].

OBJECTIVE: To better understand the acquired factor V (FV) inhibitors. METHODS: The clinical features, laboratory manifestations, treatment options and prognosis of 3 cases were reported and related literature were reviewed. RESULTS: All the 3 patients were older than 50 years without family history and related disease. Their clinical manifestations included spontaneously mucous bleeding, hematuria, epistaxis and encephalic bleeding. Laboratory test showed prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). The FV levels decreased and the presence of FV inhibitor was confirmed by Bethesda method. All patients were treated with glucocorticoid and immunosuppressive agents. The haemorrhages of two patients stopped but their coagulation test and FV level recovered slowly. One patient died from encephalic bleeding. CONCLUSIONS: Acquired FV inhibitor is a rare coagulation disorder with variable clinical symptoms. Immunosuppressive agents are effective to eliminate the inhibitors. The prognosis of acquired FV inhibitors seemed to be strictly related to the basic disease.

[Combination of rabbit antithymocyte globulin and cyclosporine A as first-line therapy for adult severe aplastic anemia].

OBJECTIVE: To analyze the efficacy and side-effects of combination of rabbit antithymocyte globulin (ATG) and cyclosporine A (CsA) as the first-line immunosuppressive therapy (IST) for adult severe aplastic anemia (SAA) patients. METHODS: Adult SAA or very severe aplastic anemia (VSAA) patients treated with rabbit ATG + CsA as first line therapy in our hospital from 2003 to 2008 were retrospectively analysed and the therapeutic response relevant factors were analysed. RESULTS: Seventy-nine patients were enrolled. Of all these patients, 6 died within 3 months after IST. The overall response rate was 82.2% and the median time to transfusion independent was 60 days. The therapeutic response rate in 32 SAA patients (100%) was significantly higher than that in 41 VSAA cases (68.3%) (P = 0.001). Patients with neutrophil response to G-CSF treatment had a higher IST response rate than those without response to G-CSF (100% vs 67.5%, P = 0.001). Sixty-one patients (77.2%) occurred serum sickness reaction. Three patients relapsed and two developed clonal hematological abnormalities after IST. The 3-year overall survival for all the patients was 88.9%. CONCLUSIONS: Rabbit ATG in combination with CsA as first-line IST for adult SAA can lead to excellent treatment outcomes with minor adverse effects.

[Immune tolerance induction in a severe hemophilia A patient with inhibitor].

OBJECTIVE: To explore the immune tolerance induction (ITI) in a severe hemophilia A patient with inhibitor, and to improve the therapeutic efficacy for patient. METHODS: The FVIII:C was assayed by one-stage method and FVIII antibody by Bethesda method. Mutation screening of FVIII gene intron 22 inversion was performed using LD-PCR. RESULTS: FVIII gene intron 22 inversion was detected in this patient. Clinical tolerance to FVIII was successfully induced after administration of the ITI regimen combined with immunosuppression. A fall of inhibitor titer from 8 BU to 0 BU after treatment for 3 months, and in vivo FVIII recovery (> 66%) was normalized. The patient had no bleeding episode in the following 6 months. CONCLUSION: This is the first case report on successful immune tolerance induction therapy in Chinese hemophilia A patient. ITI is the most effective therapy for hemophilia A with inhibitor.

[Combination of rabbit antithymocyte globulin plus cyclosporin A as first-line immunosuppressive therapy for the childhood with severe aplastic anemia.].

OBJECTIVE: To analyse the efficacy and side-effects of rabbit antithymocyte globulin (ATG) and cyclosporin A (CsA) as the first-line therapy for childhood severe aplastic anemia (SAA). METHODS: Seventy-one childhood SAA patients treated with rabbit ATG + CsA as first line therapy were retrospectively analysed. RESULTS: Seventy-one SAA patients, including 38 SAA and 33 very severe aplastic anemia (VSAA), were enrolled. The median age was 12 years. Of these patients, 3 died within 3 months after the immunosuppressive therapy (IST). The overall response rate was 67.6% (46/68) and the median time to transfusion independent was 53 days. Thirty-three patients (48.5%) obtained remission in 3 months after the IST and 45 (67.2%) in 6 months. The response rates were 57.7% (15/26), 56.5% (13/23) and 94.7% (18/19) for patients less than 10 years old, 10 - 15 year-old and 15 - 18 year-old, respectively. Sixty patients suffered from serum sickness on the IST. Three patients relapsed and another 3 unrespond patients received retreatment of IST, and one patient progressed to myelodysplastic syndromes (MDS). CONCLUSION: Rabbit ATG in combination with CsA as first line therapy for childhood SAA/VSAA can lead to overall response rate of 67.6% with minor adverse effects.

[Long-term therapeutic outcome of patients with acute promyelocytic leukemia].

OBJECTIVE: To analyze the long-term therapeutic outcome of patients with acute promyelocytic leukemia(APL). METHODS: Newly diagnosed APL patients were treated with ATRA as induction therapy followed by 3-4 courses of combined consolidation chemotherapy and 2 year maintenance therapy with ATRA and 6-MP + methrotrexate, alternatively. Patients were regularly monitored with nested RT-PCR for PML-RARalpha fusion transcript at the end of consolidation chemotherapy and in the following 4 to 5 years. RESULTS: A total of 81 patients with APL were entered the trial, 75 (92.6%) patients achieved CR. Early death (ED) rate was 6.6%. ED patients had significantly higher WBC count and higher percentage of peripheral promyelocyte than those achieved CR. Of 65 patients received consolidation, 60 (92.3%) were proved PML-RARalpha fusion gene negative at the end of the 3rd courses and 3 (4.6%) the end of the 4th courses of consolidation. The mean follow-up was 21.2 (8-64) months, 6 patients relapsed (relapse rate 9.2%). The 5-year Kaplan-Meier estimates of overall survival (OS) rate was (86.6 +/- 4.6)%. For 65 patients received consolidation therapy, the 5-year relapse-free survival (RFS) rate was 82.7%. COX-regression analyses showed only high WBC count (>10 x 10(9)/L) had an adverse prognostic influence on OS. CONCLUSION: More than 80% of APL patients treated with systemic therapy could experience long-term relapse-free survival.