Response to apheretic platelet transfusion in children of acute lymphoblastic leukemia receiving induction chemotherapy: a cross-sectional study from Bangladesh.

Background: Disease and therapy-related hypoproliferative thrombocytopenia is a significant barrier to managing acute lymphoblastic leukaemia (ALL) patients. To reduce the risk of haemorrhage, apheretic platelet transfusion is a modern, effective, and expensive option. Since most ALL patients in Bangladesh have financial constraints, this study can shed light on the magnitude of benefit regarding the effectiveness of apheretic platelet prophylactically and therapeutically in children of ALL receiving induction chemotherapy. Materials and methods: This observational cross-sectional study was conducted in the department of transfusion medicine and the department of paediatric haematology and oncology at a tertiary level hospital in Bangladesh from June 2020 to June 2021. A total of 33 cases of ALL were enroled in this study according to inclusion and exclusion criteria. After receiving written informed consent, relevant data were collected using a face-to-face interview with the guardian of the patients, thorough clinical examination, and relevant investigation. After the collection of all the required data, analysis was done by Stata (v.16). Results: Mean age of the patients was 7.39±4.46 (SD), ranging from 1 to 18 years. The majority of children were aged younger than or equal to 10 years (69.70%). Male children were slightly predominant (51.5%). Significant post-transfusion platelet increment (Median pre-transfusion count 16×103/µl vs. Median post-transfusion count 133×103/µl, P<0.001) was observed. WHO bleeding grades also improved after apheretic platelet transfusion (P<0.05). Age was a significant factor associated with corrected count increment (CCI) in both univariate and multivariate analysis. In subgroup analysis, age and gender were significant predictors of CCI in therapeutic transfusion group but not in prophylactic transfusion group. Conclusions: Significant improvement in bleeding status and platelet count was observed following apheretic platelet transfusion.

Clinical profile and serological correlation with haemolysis in DAT-positive autoimmune haemolytic anaemia patients in Bangladesh.

Discerning the type of autoimmune haemolytic anaemia (AIHA) is crucial for transfusion support and initiation of treatment. This study aimed to establish the clinical profile and serological character of red cell autoantibodies and to investigate the relationship with haemolysis in AIHA patients who were direct antiglobulin test (DAT)-positive. A total of 59 DAT-positive AIHA patients were included in this study. Clinical, laboratory and serological findings were evaluated to find the gradation of haemolysis and to investigate its correlation with age, sex, type of autoantibody and level of autoantibody. Study findings revealed that most patients (89.8%) had haemolysis, wherein moderate haemolysis (67.8%) was predominant. Weakness, palpitations, fever, pallor, tachycardia and splenomegaly were common among patients with severe and moderate haemolysis. The majority (66.1%) had an associated disorder. Warm autoantibody was the most common, followed by cold and mixed cases. The severity of haemolysis correlated strongly with the strength of the DAT reaction (Cramer V 0.636, p<0.001). These findings may be useful to clinicians while determining a treatment plan. The direct relationship between severity of haemolysis and strength of DAT needs further exploration in a large population to establish whether it can be used as a tool to formulate a treatment plan when assessing AIHA patients in low resourced countries.

Prevalence of hypogonadism in transfusion-dependent ß-thalassemia patients of Bangladesh: investigating the role of serum ferritin level as a diagnostic tool

ABSTRACT Introduction: Hypogonadism is one of the most frequent complications in transfusion-dependent thalassemia patients and early recognition and treatment is the core element in restoring impaired gonadal function. Despite the high burden of disease, relevant studies are scarcely addressing the gonadal function of such patients in Bangladesh. The pattern of gonadal function in transfusion-dependent thalassemia patients must be characterized before planning a generalized management plan. Moreover, since iron overload is a key reason behind hypogonadism in thalassemia patients, investigating the role of serum ferritin level as a diagnostic tool for hypongadism was also an aim of this study. Methods: This cross-sectional study was conducted at the Department of Transfusion Medicine of the Bangabandhu Sheikh Mujib Medical University. According to the inclusion and exclusion criteria, a total of 94 patients were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient and recorded using a pretested structured questionnaire. In addition, the laboratory assessment of serum ferritin, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol in serum were also performed. The data were analyzed using the STATA (v.16). Results: The mean age of the patients with transfusion-dependent thalassemia was 18.81 ± 4.65 (SD), with 53.3% of the patients being male. The overall prevalence of hypogonadism was 35.11%, 18.1% being normogonadotropic, 11.7% being hypogonadotropic and 5.3% being hypergonadotropic. The serum ferritin level was significantly higher (p < 0.001) in patients with hypogonadism (Eugonadal: 2,174.79 (± 749.12) ng/ml; Hypogonadal: 3,572.59 (± 1,199.49) ng/ml). The area under the receiver operating characteristic (ROC) curve of serum ferritin was high (0.83) and the p-value was highly significant (< 0.001). Conclusion: Therefore, the serum ferritin level and gonadal hormone analysis of transfusion-dependent thalassemia patients can be considered a screening tool for assessing gonadal function and early detection and prevention of hypogonadism.

Prevalence of hypogonadism in transfusion-dependent ß-thalassemia patients of Bangladesh: investigating the role of serum ferritin level as a diagnostic tool.

INTRODUCTION: Hypogonadism is one of the most frequent complications in transfusion-dependent thalassemia patients and early recognition and treatment is the core element in restoring impaired gonadal function. Despite the high burden of disease, relevant studies are scarcely addressing the gonadal function of such patients in Bangladesh. The pattern of gonadal function in transfusion-dependent thalassemia patients must be characterized before planning a generalized management plan. Moreover, since iron overload is a key reason behind hypogonadism in thalassemia patients, investigating the role of serum ferritin level as a diagnostic tool for hypongadism was also an aim of this study. METHODS: This cross-sectional study was conducted at the Department of Transfusion Medicine of the Bangabandhu Sheikh Mujib Medical University. According to the inclusion and exclusion criteria, a total of 94 patients were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient and recorded using a pretested structured questionnaire. In addition, the laboratory assessment of serum ferritin, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol in serum were also performed. The data were analyzed using the STATA (v.16). RESULTS: The mean age of the patients with transfusion-dependent thalassemia was 18.81 ± 4.65 (SD), with 53.3% of the patients being male. The overall prevalence of hypogonadism was 35.11%, 18.1% being normogonadotropic, 11.7% being hypogonadotropic and 5.3% being hypergonadotropic. The serum ferritin level was significantly higher (p < 0.001) in patients with hypogonadism (Eugonadal: 2,174.79 (± 749.12) ng/ml; Hypogonadal: 3,572.59 (± 1,199.49) ng/ml). The area under the receiver operating characteristic (ROC) curve of serum ferritin was high (0.83) and the p-value was highly significant (< 0.001). CONCLUSION: Therefore, the serum ferritin level and gonadal hormone analysis of transfusion-dependent thalassemia patients can be considered a screening tool for assessing gonadal function and early detection and prevention of hypogonadism.

Mangosteen Vinegar Rind from Garcinia mangostana Prevents High-Fat Diet and Streptozotocin-Induced Type II Diabetes Nephropathy and Apoptosis.

Type II diabetes (T2D) nephropathy, a major cause of end-stage kidney disease, progresses and develops from oxidative stress. Natural polyphenols can protect the kidney from diabetic nephropathy exerting antioxidant activities. The present approach enumerates the reno-protective and anti-apoptotic effects of mangosteen vinegar rind (MVR, a phenolic aqueous extract) against high-fat diet (5 g/day up to five weeks)-/streptozotocin (single ip, dose 30 mg/kgBW)-induced T2D nephropathy of albino mice. In vitro total phenolic content, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant capacity, and α-amylase inhibition activity as antidiabetic assay of MVR were performed. In vivo mice body weight, oral glucose, and maltose tolerance test, metabolic parameters (plasma glucose, insulin level, omeostasis model assessment-estimated insulin resistance), biochemical parameters (kidney hypertrophy, blood urea nitrogen, creatinine), oxidative stress parameters (malondialdehyde, superoxide dismutase, catalase) were estimated in an intervention study. Additionally, renal morphology and early apoptosis were observed following the H & E staining and TUNEL assay of the tissue frozen section. We found that the aqueous extract of MVR possesses potent in vitro antioxidative and antidiabetic activities. Animal intervention results showed that MVR 100, 200 mg/kgBW, and Glibenclamide 60 mg/kgBW treatments significantly improved (P < 0.05) the abovementioned parameters compared to the diabetic control group. Furthermore, treatments also significantly restored (P < 0.05) kidney histological alterations and reduced cellular apoptosis compared to the diabetic control group. These findings concluded that MVR treatments significantly modulated the glucose intolerance, metabolic alterations, and oxidative stress-induced pathological alterations and cellular apoptosis of diabetic kidney. PRACTICAL APPLICATION: Garcinia mangostana, a polyphenol rich natural product, is obtained from the tropical rain forest area of Southeast Asian countries and processes diverse biological activities including antioxidant, anti-proliferative, anti-inflammatory, anti-carcinogenic, and so on. This research first time focuses on the nephro-protective and anti-apoptotic effects of mangosteen vinegar rind (MVR) from the mangosteen fruit pericarp. Our study provides the efficient data to prove the beneficial effect of MVR as a dietary supplement for the prevention and management of diabetic nephropathy.

Anti-HBc Screening of Blood Donors in Bangladesh: Relevance to Containment of HBV Propagation.

OBJECTIVES: To avoid further transmission of hepatitis B virus (HBV) infection, blood is tested for hepatitis B surface antigen (HBsAg) before transfusion. However, post-transfusion hepatitis B has been detected in clinics after transfusion of HBsAg-negative blood. The study presented here was undertaken to assess if HBsAg-negative blood is free from HBV or not. METHODS: Sera were collected from 398 blood donors who were negative for HBsAg. Out of 398 blood samples, antibody to hepatitis B core antigen (ant-HBc) was detected in 82 sera samples. HBV DNA was evaluated in HBsAg-negative, anti-HBc-positive sera. HBsAg, hepatitis B e antigen (HBeAg), antibody to HBeAg (anti-HBe), and anti-HBc in the sera were measured by an enzyme-linked immunosorbent assay (ELISA). HBV DNA was quantified by a real time polymerase chain reaction (PCR). RESULTS: Out of 82 HBsAg-negative, anti-HBc-positive sera samples, HBV DNA were detected in the sera of 7 voluntary blood donors. Out of these 7 subjects, all were negative for HBeAg. The levels of ALT were more than 30 IU/L in 6 of 7 HBVDNA-positive subjects and it was above upper limit of normal (>42 IU/ml) in one subject. CONCLUSIONS: The present recommendation about blood transfusion of HBsAg-negative blood system is not capable of blocking HBV transmission to blood recipients. Although advanced countries have adopted nucleic acid testing (NAT) for preventing HBV transmission, developing countries may apply anti-HBc testing and ALT estimation before blood transmission.

Proteomic analysis for inhibitory effect of chitosan oligosaccharides on 3T3-L1 adipocyte differentiation.

In the present study, we performed a differential proteomic analysis using 2-DE combined with MS to clarify the molecular mechanism for the suppressive effect of chitosan oligosaccharides (CO) during differentiation of adipocyte 3T3-L1. Cell differentiation was significantly inhibited by CO at the concentration of 4 mg/mL. Protein mapping of adipocyte homogenates by 2-DE revealed that numerous protein spots were differentially altered in response to CO treatment. Out of 50 identified proteins showing significant alterations, six were up-regulated and 44 were down-regulated by CO treatment in comparison to control mature adipocytes. Among them, most of the proteins are associated with lipid metabolism, cytoskeleton, and redox regulation, in which the levels of farnesyl diphosphate synthetase (FDS), dedicator of cytokinesis 9 (DOCK9), and chloride intracellular channel 1 (CLIC1) were significantly reduced (>two-fold) with CO treatment. These results have not previously been examined in the context of adipogenesis, and thus can be used as novel biomarkers. Taken together with immunoblot analysis, it was concluded that the inhibitory effect of CO on adipocyte differentiation was mediated by C/EBPalpha and PPARgamma pathway through significant downregulations of important adipogenic molecules such as fatty acid binding protein and glucose transporter 4.

Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation.

The anthracyclines are a group of antibiotics that are among the most potent chemotherapeutic agents. They are highly effective against a broad spectrum of malignancies, including lymphoma, gastric cancer, small cell lung cancer, sarcoma, and breast cancer. Unfortunately, these agents also exhibit a well-recognized cumulative-dose related cardiotoxic profile that limits the extent to which they can be used safely. In clinical practice, most clinicians limit the cumulative dose of doxorubicin (the most widely used agent in this group) to 400-450 mg/m2, but considerable cardiac damage is now known to occur at cumulative dosages considerably below this level. Regimens using newer combinations of agents, the most widely studied of which is the monoclonal antibody trastuzumab, are known to augment the cardiotoxicity of anthracyclines. The application of nanotechnology to medicine involves the use of devices that will interact with the body at the molecular level. These methods can lead to target and tissue specific clinical application, often with minimal or reduced side effects. Liposomal preparations incorporate such technology, thereby altering some important characteristics of the parent compound and facilitating concentration at the tumor site. In the case of liposomal doxorubicin, cardiotoxicity is reduced significantly. This review summarizes the important information on the liposomal preparation of anthracyclines.

Role of transesophageal echocardiography guided cardioversion in patients with atrial fibrillation, previous left atrial thrombus and effective anticoagulation.

AIMS: The value of transesophageal echocardiography (TEE) to prevent cardioversion-related thromboembolic events in patients with atrial fibrillation (AF) and left atrial (LA) thrombus is unclear. We compared the embolic risk associated with a strategy of follow-up TEE-guided direct-current cardioversion (DCCV) with that of blind DCCV in patients with AF, pre-existing LA thrombus and effective anticoagulation. METHODS AND RESULTS: We identified 67 subjects with TEE-documented LA appendage thrombi from a total of 520 consecutive patients with symptomatic non-rheumatic AF who were referred to us for elective DCCV. All patients received at least 4 weeks of effective warfarin therapy (target international normalized ratio, 2 to 3) before and after DCCV. At time of DCCV, 20 patients had TEE and 47 did not. There were no clinical and echocardiographic differences between the two groups. Thrombus resolution was documented in 18 (90%) patients. After a median follow-up of 4 weeks, two transient ischemic attacks were observed in patients who were blindly cardioverted and one in patients belonging to the TEE group. Sinus rhythm was documented at the time of each thromboembolic event. By multiple logistic regression analysis the TEE strategy was not associated with lower risk of thromboembolism as compared to blind DCCV (odds ratio 1.37; 95% confidence interval, 0.16% to 15.86%; p=0.20). CONCLUSION: In patients with AF, LA thrombus and effective anticoagulation, there is no difference in the risk of clinical thromboembolism between DCCV with or without follow-up TEE. Benefits of warfarin are related to thrombus resolution and prevention of new thrombus formation.

Reversible right ventricular dysfunction in patients with HIV infection.

Human immunodeficiency virus-related cardiomyopathy is characterized by global left ventricular (LV) dysfunction commonly associated with biventricular dilation. Human immunodeficiency virus (HIV) cardiomyopathy carries a poor prognosis, and the role of antiretroviral therapy in the reversal of heart failure is not very clear. We report two patients with HIV infection who presented with severe right ventricular (RV) dysfunction in the absence of pulmonary parenchymal, pulmonary arterial and left ventricular myocardial involvement. During the period of intensive antiretroviral therapy, the symptoms of right heart failure progressively and remarkably improved. This was accompanied by normalization of right ventricular size and RV function documented by repeat echocardiograms. Given that the serologic tests for opportunistic infections were negative, and the RV function improvement correlated with a decrement in the viral load, it is likely that the cardiomyopathy was due to direct infection by HIV. These cases illustrate that there can be isolated involvement of the right heart in the absence of lung, significant pulmonary vascular and left ventricular disease, and also that the antiretroviral therapy might reverse the cardiomyopathy.

Assessment of left atrial appendage by live three-dimensional echocardiography: early experience and comparison with transesophageal echocardiography.

BACKGROUND: Live Three-Dimensional Echocardiography (L3D, Sonos 7500, Philips) has the potential to visualize all cardiac structures including left atrial appendage (LAA). We tested the feasibility of evaluating LAA by L3D and compared the findings to transthoracic echocardiography (2D) and in a subset of patients with transesophageal echocardiography (TEE). METHODS: L3D images were obtained in 204 consecutive patients referred for routine 2D or TEE. We performed wide-angled acquisitions from parasternal and apical views. TomTec system (4D Cardio-view, RT 1.2) was used to visualize LAA from multiple vantage points. RESULTS: LAA was adequately visualized by L3D in 139 of 204 (68.1%) patients. L3D visualization was dependent on image quality, suboptimal in 100 and diagnostic in 104 patients. Overall, LAA was visualized in 93 (45.5%) patients by 2D compared to 139 (68.1%) by L3D (P < 0.0001). In 100 patients with suboptimal image quality by L3D, LAA visualization was 16% by 2D and 35% by L3D, whereas in 104 patients with diagnostic images, LAA was visualized in 77 (74%) by 2D and in all 104 (100%) patients by L3D (P < 0.0001). In 37 patients referred for transesophageal echocardiography (TEE), live three-dimensional echocardiography (L3D) visualized left atrial appendage (LAA) in 34 patients with diagnostic image quality. Eight patients with LAA thrombi on TEE had thrombi detected by L3D as well. All patients with LAA thrombus had enlarged LA by both 2D and TEE. CONCLUSIONS: L3D is a promising technique in evaluation of LAA with and without thrombi. In patients with good quality transthoracic images L3D may be used as a screening tool in assessment of LAA.

Enhanced cardioprotection against ischemia-reperfusion injury with combining sildenafil with low-dose atorvastatin.

PURPOSE: Both ATV and SL reduce myocardial infarct size (IS) by enhancing expression and activity of NOS isoforms. We investigated whether atorvastatin (ATV) and sildenafil (SL) have synergistic effects on myocardial infarct size (IS) reduction and enhancing nitric oxide synthase (NOS) expression. METHOD: Rats were randomized to nine groups: ATV-1 (1 mg/kg/d); ATV-10 (10 mg/kg/d); SL-0.7 (0.7 mg/kg); SL-1 (1 mg/kg); ATV-1 + SL-0.7; water alone (controls); 1400W (iNOS inhibitor; 1 mg/kg); ATV-10 + 1400W; and ATV-1 + SL-0.7 + 1400W. ATV was administered orally for 3 days. SL was administered intraperitoneally 18 h before surgery and 1400W intravenously 15 min before surgery. Rats either underwent 30 min ischemia-4 h reperfusion or the hearts were explanted for immunoblotting and enzyme activity tests without being exposed to ischemia. RESULTS: IS (% risk area, mean +/- SEM) was smaller in the ATV-10 (13 +/- 1%), SL-1 (11 +/- 2%), SL-0.7 (18 +/- 2%) and ATV-1 + SL-0.7 (9 +/- 1%) groups as compared with controls (34 +/- 3%; P < 0.001), whereas ATV-1 had no effect (29 +/- 2%). ATV-1 + SL-0.7 (9 +/- 1%) reduced IS more than SL-0.7 alone (p = 0.012). 1400W abrogated the protective effect of ATV-10 (35 +/- 3%) and ATV-1 + SL-0.7 (34 +/- 1%). SL-0.7 and ATV-10 increased phosphorylated endothelial (P-eNOS; 210 +/- 2.5% and 220 +/- 8%) and inducible (iNOS; 151 +/- 1% and 154 +/- 1%) NOS expression, whereas ATV-1 did not. These changes were significantly enhanced by ATV-1 + SL-0.7 (P-eNOS, 256 +/- 2%, iNOS 195 +/- 1%). SL-1 increased P-eNOS (311 +/- 22%) and iNOS (185 +/- 1%) concentrations. CONCLUSIONS: Combining low-dose ATV with SL augments the IS limiting effects through enhanced P-eNOS and iNOS expression.

Arsenic exposure from drinking-water and carotid artery intima-medial thickness in healthy young adults in Bangladesh.

Epidemiological studies have linked high levels (>200 microg/L) of chronic exposure to arsenic in drinking-water with elevated risks of several vascular diseases. In this pilot study, the association between low-level arsenic exposure and carotid artery intimal-medial thickness (IMT) was evaluated among 66 healthy, normotensive, relatively young individuals (mean age 35 years) participating in the ongoing Health Effects of Arsenic Longitudinal Study in Bangladesh. Participants with a higher carotid IMT (>0.75 mm) in general had higher levels of past chronic exposure of arsenic than those with a lower carotid IMT (< or = 0.75 mm). Although the differences in average arsenic exposure between the two groups were not statistically significant, the findings suggest a possible association between low-level arsenic exposure from drinking-water and carotid atherosclerosis, warranting the need for larger studies.

Stress-induced right ventricular ischemia in recurrent pulmonary outflow stenosis in repaired tetralogy of fallot.

Radionuclide uptake by the right ventricle during myocardial perfusion imaging is minimal compared with the left ventricular myocardium and is not given much importance. However, right ventricular hypertrophy from pressure or volume overload may increase right ventricular radiotracer uptake and demonstrate reversible stress-induced perfusion abnormalities in the presence of normal coronary arteries. We report a case of right ventricular ischemia secondary to right ventricular hypertrophy from recurrent right ventricular outflow tract stenosis in a patient with repaired tetralogy of Fallot. Advances in the management of congenital heart disease have led to more patients surviving to adulthood. These patients subsequently present to cardiologists in adulthood with sequelae or complications arising from previous surgery undertaken during childhood.

Acute coronary syndrome induced by intravenous ephedrine in pregnant woman with normal coronaries.

Intravenous ephedrine administered during a C-section was observed to cause an acute coronary syndrome in a pregnant woman with normal coronaries. The patient developed sub-sternal chest pain, was noted to have 10 beats of non-sustained ventricular tachycardia, ST abnormalities were observed on her ECG and cardiac enzymes were elevated. The patient had normal coronary arteries by angiogram and during a one-year period of follow up no further cardiac events occurred.

Monomorphic ventricular tachycardia: a late complication of percutaneous alcohol septal ablation for hypertrophic cardiomyopathy.

Percutaneous alcohol septal ablation has emerged as a promising treatment option for patients with symptomatic hypertrophic obstructive cardiomyopathy. Although the procedure involves an alcohol-induced myocardial infarction and results in a substrate potentially conducive to re-entrant tachyarrhythmias, late-occurring ventricular arrhythmias have not been described. We report a case of monomorphic ventricular tachycardia occurring several days after alcohol septal ablation. Patients with hypertrophic cardiomyopathy undergoing alcohol septal ablation should be considered for prophylactic placement of implantable cardioverter defibrillator.

Abciximab treatment for obstructive prosthetic aortic and mitral valve thrombosis in the presence of large thrombi, cardiogenic shock, and acute evolving embolic stroke.

Obstructive thrombosis of left-sided mechanical prosthetic valves is a life-threatening complication. Intravenous thrombolytic therapy is contraindicated due to risk of clot embolization and surgical treatment is often required for hemodynamically unstable patients. We report for the first time the successful use of abciximab in the management of a patient in cardiogenic shock with multiple prosthetic valve obstructive thrombosis and evolving embolic stroke. Serial Doppler echocardiography and cinefluoroscopy demonstrated resolution of thrombi, improvements in transvalvular gradients and improvement in leaflet motion. This observation suggests abciximab should be considered as a therapeutic option in the treatment of obstructed prosthetic heart valves.