Expert Opinions on the Management of Hemophilia A in India: The Role of Emicizumab.

Hemophilia A (HA) is a genetic disorder of hemostasis associated with a deficiency or reduced activity of clotting factor VIII (FVIII). This disorder remains unacceptably underdiagnosed in India. Early diagnosis and appropriate management of HA can substantially prevent morbidity and mortality. Currently, HA is managed with regular replacement therapy using standard or extended half-life FVIII concentrates or non-factor drug products. The challenges associated with FVIII concentrates include plateauing of drug effect, issues with its administration and adherence to treatment, breakthrough bleeds, and the development of inhibiting antibodies against administered clotting factors. Emicizumab is a bispecific antibody, launched in India in April 2019, for managing patients with HA. To investigate the role of emicizumab in Indian patients with HA, opinions were sought from 13 eminent hematologists and experts from India on the effectiveness of emicizumab in preventing all bleeds, spontaneous bleeds, perioperative bleeds, and intracranial hemorrhage; resolving target joints; and reducing the rate of hospitalizations and fatality associated with HA in children and adults, with or without inhibitors. The benefits of emicizumab over traditional FVIII concentrates include the subcutaneous route of delivery, less frequent dosing, and a lack of inhibitor development, in addition to providing sustained hemostasis without in-depth monitoring. It is a safe and effective management option for all HA patients, especially for patients with certain archetypes, such as those with inhibitors, those with high annualized bleed rates, those living far away from hemophilia care centers, pediatric patients and infants with intravenous access challenges, and those with a history of life-threatening bleeding events.

Correction: Expert Opinions on the Management of Hemophilia A in India: The Role of Emicizumab.

[This corrects the article DOI: 10.7759/cureus.58941.].

Subconjunctival Delivery of Sorafenib-Tosylate-Loaded Cubosomes for Facilitated Diabetic Retinopathy Treatment: Formulation Development, Evaluation, Pharmacokinetic and Pharmacodynamic (PKPD) Studies.

Diabetic retinopathy (DR) is a microvascular complication associated with vascular endothelial growth factor (VEGF) overexpression. Therapeutic delivery to the retina is a challenging phenomenon due to ocular biological barriers. Sorafenib tosylate (ST) is a lipophilic drug with low molecular weight, making it ineffective at bypassing the blood-retinal barrier (BRB) to reach the target site. Cubosomes are potential nanocarriers for encapsulating and releasing such drugs in a sustained manner. The present research aimed to compare the effects of sorafenib-tosylate-loaded cubosome nanocarriers (ST-CUBs) and a sorafenib tosylate suspension (ST-Suspension) via subconjunctival route in an experimental DR model. In this research, ST-CUBs were prepared using the melt dispersion emulsification technique. The distribution of prepared nanoparticles into the posterior eye segments was studied with confocal microscopy. The ST-CUBs were introduced into rats' left eye via subconjunctival injection (SCJ) and compared with ST-Suspension to estimate the single-dose pharmacokinetic profile. Streptozotocin (STZ)-induced diabetic albino rats were treated with ST-CUBs and ST-Suspension through the SCJ route once a week for 28 days to measure the inhibitory effect of ST on the diabetic retina using histopathology and immunohistochemistry (IHC) examinations. Confocal microscopy and pharmacokinetic studies showed an improved concentration of ST from ST-CUBs in the retina. In the DR model, ST-CUB treatment using the SCJ route exhibited decreased expression levels of VEGF, pro-inflammatory cytokines, and adhesion molecules compared to ST-Suspension. From the noted research findings, it was concluded that the CUBs potentially enhanced the ST bioavailability. The study outcomes established that the developed nanocarriers were ideal for delivering the ST-CUBs via the SCJ route to target the retina for facilitated DR management.

miR-486-5p: A Prognostic Biomarker for Chronic Myeloid Leukemia.

MicroRNA miR-486-5p has been reported as a potential biomarker for diagnosis, prognosis, and as a therapeutic target in various cancers. In this study, we analyzed alterations in the expression of miR-486-5p in chronic Myeloid Leukemia (CML) patients. Initially, the expression of miR-486-5p was studied in the BCR-ABL1+ve CML K562 cell line by quantitative real-time polymerase chain reaction (qRT-PCR). The results indicated that the miR-486-5p expression was significantly upregulated in K562 cells after imatinib exposure, as compared to untreated K562 cells (p-value = 0.047). These observations were corroborated by a hospital-based study of the miR-486-5p expression in peripheral blood leucocytes of 36 CML patients in the chronic phase (CP) and compared with age and sex-matched healthy volunteers as control subjects. qRT-PCR-based quantification revealed significant downregulation of the miR-486-5p expression in newly diagnosed untreated CP-CML patients' samples (2-ΔCt = 13.19 ± 14.41) as compared to control samples (2-ΔCt = 254.5 ± 274.8) (p-value < 0.0001). Levels of miR-486-5p were found to be distinctly elevated in the post-imatinib treatment samples of CML patients (2-ΔCt = 469.7 ± 312.9) as compared to pre-treatment samples (p-value < 0.0001). CML patients' clinical and hematological responses to imatinib therapy (oral dose of 400 mg OD) were monitored for 12 months. The correlation of pre-treatment miR-486-5p levels with Sokal score indicated that patients with a higher expression of miR-486-5p had better prognoses. Patients with higher pre-imatinib miR-486-5p levels also showed a major hematologic response to imatinib in a shorter time and vice versa. To the best of our knowledge, this is the first report of alterations in the miR-486-5p expression in peripheral blood leucocytes of CML patients. Our observations support a tumor suppressor role of miR-486-5p in CML. The downregulation of the miR-486-5p expression may be critically important in the disease progression of CML patients. The upregulation of the miR-486-5p expression in post-imatinib exposure K562 cells and CML patients after 12 months of imatinib treatment suggests an onco-suppressor effector role of miR-486-5p in the BCR-ABL downstream signaling pathway. miR-486-5p can be explored as a novel biomarker for the early detection of CML.

Single-Dose Prophylactic Antibiotic Versus Extended Usage for Four Days in Clean-Contaminated Oncological Surgeries: a Randomized Clinical Trial.

The optimal duration of prophylactic antimicrobial usage in clean-contaminated elective oncological surgeries is not clear. This single-center randomized trial evaluated the effectiveness of single-dose antimicrobial prophylaxis in clean-contaminated surgeries for the reduction of surgical site infection (SSI). Between April 2018 and January 2019, 315 patients undergoing major oncological clean-contaminated surgeries where the gastrointestinal or genital tract was opened under controlled conditions were randomized into 2 groups i.e., single dose versus extended dose groups. The single dose group received a 1.5 g dose of cefuroxime immediately before surgery while the extended group received the same dose of cefuroxime thrice daily for 4 days from the day of surgery till postoperative day 3. In addition, patients undergoing esophageal and colorectal surgeries received metronidazole. The overall SSI rate of the single dose group was not significantly different from that of the extended group (11.3% vs. 14.7%, respectively, p 0.40), with absolute difference of 3.4% and relative risk of 0.85 (95% C.I, 0.59 to 1.22). The rate of remote site infection was also not different between the two groups (14.4% vs 10.2%, p 0.31) with absolute difference of 4.2% and relative risk 1.19 (95% C.I, 0.89 to 1.59). In univariate analysis, parameters like nodal dissection, colorectal surgery, smoking, and hospital stay were significantly associated with SSI. In multivariate analysis, age, smoking, nodal dissection, and hospital stay retained significance. Single-dose antimicrobial prophylaxis is as effective as extended usage for 4 days in the prevention of postoperative SSI in patients undergoing clean-contaminated major oncological surgeries. Trial was registered with the clinical trial registry of India (CTRI/2018/06/014344).

Risk of COPD due to indoor air pollution from biomass cooking fuel: a systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality in developing nations. In this meta-analysis, we aimed to determine the association between indoor air pollution and risk of COPD. Database searches were conducted using indoor air pollution, biomass and COPD related terms to identify relevant articles. The eligible studies were case-control, retrospective cohort, cross-sectional studies and conducted in adults that assessed COPD using any diagnostic criteria. A total of 35 studies with 73,122 participants were included. The pooled analysis showed that exposure to indoor air pollution due to solid biomass fuels increased risk of COPD by 2.65 (95% confidence interval [CI] 2.13-3.31; n = 73,122) and chronic bronchitis by 2.89 (95% CI 2.18-3.82) times more compared to non-biomass fuels. The risk of COPD was higher in Africa region (odds ratio [OR] 3.19), Asia (OR 2.88), South America (OR 2.15), Europe (OR 2.30) and North America (OR 2.14). The results of our meta-analysis indicated that exposure to indoor air pollution due to biomass smoke is strongly associated with COPD.Abbreviations: CS: cross-sectional; CC: case-control; NR: not reported; ATS: American Thoracic Society; BMRC: British Medical Research Council; GOLD: Global Initiative for Obstructive Lung Disease; IAP: indoor air pollution; BMF: biomass fuel; CB: chronic bronchitis; OR: odds ratio; UCI; upper confidence interval; LCI: lower confidence interval; COPD: chronic obstructive pulmonary disease.

HAEMOcare: The First International Epidemiological Study Measuring Burden of Hemophilia in Developing Countries.

Introduction Optimizing hemophilia care remains challenging in developing countries. Burden-of-disease studies are important to develop strategies for improving hemophilia care. Aim The HAEMOcare study evaluated the factors contributing to hemophilia-related orthopedic disease burden in developing countries. Methods HAEMOcare was a noninterventional, cross-sectional, epidemiological study conducted in Algeria, India, Morocco, Oman, and South Africa. Male patients with severe hemophilia ( N = 282) aged ≥6 years, without or with inhibitors, being treated on-demand for bleeding were included. Hemophilia-related orthopedic clinical and functional status was assessed using the Hemophilia Joint Health Score (HJHS), radiological status with the Pettersson Score, and quality of life with the EuroQol five-dimension questionnaire (EQ-5D-3L). Direct and indirect economic costs of hemophilia care were also calculated. Results Patients (mean [standard deviation, SD] age: 20.8 [10.6] years) experienced a mean annualized bleeding rate of 25.8. Overall mean (SD) HJHS and Pettersson score were 17.9 (12.8) and 15.0 (13.5), respectively; scores were similar between patients without or with inhibitors ( p = 0.21 and 0.76, respectively). Approximately 70% of adults reported problems relating to pain/discomfort and mobility parameters in the EQ-5D-3L. Mean distance to a hemophilia treatment center (HTC) was 79.4 km. As expected, total costs of hemophilia were statistically significantly higher in patients with inhibitors versus without inhibitors ( p = 0.002). Conclusion Inadequate access to HTCs and expert care, along with high bleeding rates, led to equivalent hemophilia-related orthopedic morbidity between hemophilia patients without and with inhibitors. HAEMOcare documented the economic and disease burdens associated with suboptimal hemophilia care in developing countries.

Priapism as a Debut Presentation of Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a chronic myeloproliferative disorder that usually presents with high white blood cell counts and massive splenomegaly. Priapism is a rare manifestation of CML and is mostly due to hyperleukocytosis. Its debut appearance as a sign of hematological dyscrasia is a rare event. Priapism occurring in a setting of any leukemia is both a medical and a urological emergency that requires immediate local therapy, symptomatic treatment, cytoreductive therapy and early initiation of targeted therapy. This case report describes priapism as an unusual presentation of CML and its importance in the work-up and management of patients presenting with priapism.

Study on Coagulation Factor VIII and Fibrinogen Levels in Patients with Thyroid Disorders.

INTRODUCTION: A kaleidoscope of coagulation disorders has been reported in patients with thyroid dysfunctions. Globally, these disorders involve both primary and secondary hemostasis and range from subclinical laboratory abnormalities to, more rarely, life-threatening hemorrhages or thrombotic events. While overt hypothyroidism appears to be associated with a bleeding tendency, hyperthyroidism emerged to have an increased risk of thrombotic events. As a controversy, subclinical hypothyroidism and mild hypothyroidism have been reported as prothrombotic state. The mechanisms involved in these observations are also not conformed. OBJECTIVE: To study the levels of prothrombotic coagulation factor VIII and fibrinogen in patients with thyroid disorder at baseline and to correlate the change in these factors after attaining euthyroid state by treatment. STUDY DESIGN: This was a longitudinal interventional study. SUBJECTS AND METHODS: Forty patients were recruited based on the inclusion and exclusion criteria, and their coagulation profile (prothrombin time, aPTT, Factor VIII, and fibrinogen levels), routine hematological, and biochemical profile was done at baseline and 6 weeks after attaining euthyroid state. RESULTS AND CONCLUSION: Hyperthyroidism and mild hypothyroidism were found to be hypercoagulable states and moderate-to-severe hypothyroidism as hypocoagulable states. Nevertheless, further observational and intervention studies are needed to provide more definitive information on the clinical relevance of this association, along with the potential implication for prevention and treatment of coagulation/fibrinolytic abnormalities in patients with thyroid dysfunction.

PDGFRα promoter polymorphisms and expression patterns influence risk of development of imatinib-induced thrombocytopenia in chronic myeloid leukemia: A study from India.

Platelet-derived growth factor receptor has been implicated in many malignant and non-malignant diseases. Platelet-derived growth factor receptor-α is a tyrosine kinase and a side target for imatinib, a revolutionary drug for the treatment of chronic myeloid leukemia that has dramatically improved the survival of chronic myeloid leukemia patients. Given the importance of platelet-derived growth factor receptor in platelet development and its inhibition by imatinib, it was intriguing to analyze the role of platelet-derived growth factor receptor-α in relation to imatinib treatment in the development of imatinib-induced thrombocytopenia in chronic myeloid leukemia patients. We hypothesized that two known functional polymorphisms, +68GA insertion/deletion and -909C/A, in the promoter region of the platelet-derived growth factor receptor-α gene may affect the susceptibility of chronic myeloid leukemia patients receiving imatinib treatment to the development of thrombocytopenia. A case-control study was conducted among a cohort of chronic myeloid leukemia patients admitted to the Lok Nayak Hospital, New Delhi, India. A set of 100 patients of chronic myeloid leukemia in chronic phase and 100 age- and sex-matched healthy controls were studied. After initiation of imatinib treatment, the hematological response of chronic myeloid leukemia patients was monitored regularly for 2 years, in which the development of thrombocytopenia was the primary end point. Platelet-derived growth factor receptor-α promoter polymorphisms +68GA ins/del and -909C/A were studied by allele-specific polymerase chain reaction. Platelet-derived growth factor receptor-α messenger RNA expression was evaluated by quantitative real-time polymerase chain reaction. The messenger RNA expression results were expressed as 2-Δct ± standard deviation. The distribution of +68GA ins/del promoter polymorphism genotypes differed significantly between the thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups (p < 0.0001). Moreover, +68GA del/del and ins/del genotypes in imatinib-treated chronic myeloid leukemia patients were associated with an increased risk of developing thrombocytopenia, with odds ratios 6.5 (95% confidence interval = 2.02-0.89, p = 0.001) and 6.0 (95% confidence interval = 2.26-15.91, p = 0.0002), respectively. Similarly, -909C/A promoter polymorphism genotype distribution also differed significantly between thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups (p = 0.02), and a significantly increased risk of imatinib-induced thrombocytopenia was associated with -909C/A polymorphism mutant homozygous (AA) genotypes the odds ratio being 7.7 (95% confidence interval 1.50 to 39.91, p = 0.009). However, no significant risk of imatinib-induced thrombocytopenia was found to be associated with heterozygous genotype (-909C/A) with odds ratio 1.9 (95% confidence interval = 0.86-4.56, p = 1.14). Platelet-derived growth factor receptor-α messenger RNA expression was significantly higher in chronic myeloid leukemia patients compared to controls (p = 0.008). Moreover, patients with imatinib-induced thrombocytopenia had a significantly lower platelet-derived growth factor receptor-α messenger RNA expression, compared to patients without thrombocytopenia (p = 0.01). A differential expression of platelet-derived growth factor receptor-α messenger RNA was observed with respect to different +68 GA ins/del and -909C/A polymorphism genotypes. The +68GA deletion allele and -909A allele were significantly associated with lower expression of platelet-derived growth factor receptor-α messenger RNA. The platelet-derived growth factor receptor-α +68GA del/del, +68GA ins/del, and -909AA genotypes are associated with an increased risk of developing thrombocytopenia in imatinib-treated chronic myeloid leukemia patients. A significantly lower platelet-derived growth factor receptor-α messenger RNA expression accompanies the +68GA deletion allele in an allele dose-dependent manner. Platelet-derived growth factor receptor-α -909AA genotype is also associated with lower expression of platelet-derived growth factor receptor-α. The downregulation of platelet-derived growth factor receptor-α expression may play a causative role in imatinib-induced thrombocytopenia, a common side effect, in the subset of chronic myeloid leukemia patients with platelet-derived growth factor receptor-α +68 GA ins/del, +68 GA del/del, and -909C/A genotypes.

Chemical characteristics and source apportionment of PM2.5 using PCA/APCS, UNMIX, and PMF at an urban site of Delhi, India.

The present study investigated the comprehensive chemical composition [organic carbon (OC), elemental carbon (EC), water-soluble inorganic ionic components (WSICs), and major & trace elements] of particulate matter (PM2.5) and scrutinized their emission sources for urban region of Delhi. The 135 PM2.5 samples were collected from January 2013 to December 2014 and analyzed for chemical constituents for source apportionment study. The average concentration of PM2.5 was recorded as 121.9 ± 93.2 µg m-3 (range 25.1-429.8 µg m-3), whereas the total concentration of trace elements (Na, Ca, Mg, Al, S, Cl, K, Cr, Si, Ti, As, Br, Pb, Fe, Zn, and Mn) was accounted for ∼17% of PM2.5. Strong seasonal variation was observed in PM2.5 mass concentration and its chemical composition with maxima during winter and minima during monsoon seasons. The chemical composition of the PM2.5 was reconstructed using IMPROVE equation, which was observed to be in good agreement with the gravimetric mass. Source apportionment of PM2.5 was carried out using the following three different receptor models: principal component analysis with absolute principal component scores (PCA/APCS), which identified five major sources; UNMIX which identified four major sources; and positive matrix factorization (PMF), which explored seven major sources. The applied models were able to identify the major sources contributing to the PM2.5 and re-confirmed that secondary aerosols (SAs), soil/road dust (SD), vehicular emissions (VEs), biomass burning (BB), fossil fuel combustion (FFC), and industrial emission (IE) were dominant contributors to PM2.5 in Delhi. The influences of local and regional sources were also explored using 5-day backward air mass trajectory analysis, cluster analysis, and potential source contribution function (PSCF). Cluster and PSCF results indicated that local as well as long-transported PM2.5 from the north-west India and Pakistan were mostly pertinent.

A Study of Haematological and Haemostasis Parameters and Hypercoagulable State in Tuberculosis Patients in Northern India and the Outcome with Anti-Tubercular Therapy.

INTRODUCTION: Tuberculosis is one of the leading infectious diseases with high morbidity and mortality in the developing countries. Tuberculosis is also rarely associated with hypercoagulable state and very limited literature is available on this association. AIM: To study the haematological and haemostasis laboratory parameters, to correlate the abnormalities for a hypercoagulable state and to study the outcome with anti-tubercular therapy. MATERIALS AND METHODS: The study population included 128 patients with newly diagnosed tuberculosis. Anti-tubercular therapy naïve patients were studied for haemostasis parameters like Prothrombin time, Activated Partial Thromboplastin time, Factor VIII, Fibrinogen and D-dimer and haematological parameters like Haemoglobin, White Blood Cells, Platelet count, Erythrocyte Sedimentation Rate (ESR), Lactate Dehydrogenase, C-reactive protein and albumin. At the end of the second month of anti-tubercular therapy, results were compared and analysed using statistical package for the social sciences software (SPSS). RESULTS: Prothrombin levels were deranged in 50%. Activated Partial Thromboplastin time levels were deranged in 18%. Deranged Factor VIII levels were found in 35.15%. Fibrinogen levels were deranged in 57%. D-Dimer positivity was found in 57.8% patients. Anaemia was found in 75.78%, Leukocytosis in 49.21%, Thrombocytopenia in 37.5% and Hypoalbuminaemia in 75%. ESR levels were raised in 98.43%. Follow up comparison analysis revealed significant p-value for all the parameters except Factor VIII and Activated Partial Thromboplastin time. Similar trend was also observed within different groups of Tuberculosis patients. CONCLUSION: Tuberculosis does favour a hypercoagulable state with increased risk of developing thrombosis and significant improvement with the anti-tubercular treatment alone.

Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition.

IMPORTANCE: Midlife vascular risk factors have been associated with late-life dementia. Whether these risk factors directly contribute to brain amyloid deposition is less well understood. OBJECTIVE: To determine if midlife vascular risk factors are associated with late-life brain amyloid deposition, measured using florbetapir positron emission tomography (PET). DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities (ARIC)-PET Amyloid Imaging Study, a prospective cohort study among 346 participants without dementia in 3 US communities (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi) who have been evaluated for vascular risk factors and markers since 1987-1989 with florbetapir PET scans in 2011-2013. Positron emission tomography image analysis was completed in 2015. EXPOSURES: Vascular risk factors at ARIC baseline (age 45-64 years; risk factors included body mass index ≥30, current smoking, hypertension, diabetes, and total cholesterol ≥200 mg/dL) were evaluated in multivariable models including age, sex, race, APOE genotype, and educational level. MAIN OUTCOMES AND MEASURES: Standardized uptake value ratios (SUVRs) were calculated from PET scans and a mean global cortical SUVR was calculated. Elevated florbetapir (defined as a SUVR >1.2) was the dependent variable. RESULTS: Among 322 participants without dementia and with nonmissing midlife vascular risk factors at baseline (mean age, 52 years; 58% female; 43% black), the SUVR (elevated in 164 [50.9%] participants) was measured more than 20 years later (median follow-up, 23.5 years; interquartile range, 23.0-24.3 years) when participants were between 67 and 88 (mean, 76) years old. Elevated body mass index in midlife was associated with elevated SUVR (odds ratio [OR], 2.06; 95% CI, 1.16-3.65). At baseline, 65 participants had no vascular risk factors, 123 had 1, and 134 had 2 or more; a higher number of midlife risk factors was associated with elevated amyloid SUVR at follow-up (30.8% [n = 20], 50.4% [n = 62], and 61.2% [n = 82], respectively). In adjusted models, compared with 0 midlife vascular risk factors, the OR for elevated SUVR associated with 1 vascular risk factor was 1.88 (95% CI, 0.95-3.72) and for 2 or more vascular risk factors was 2.88 (95% CI, 1.46-5.69). No significant race × risk factor interactions were found. Late-life vascular risk factors were not associated with late-life brain amyloid deposition (for ≥2 late-life vascular risk factors vs 0: OR, 1.66; 95% CI, 0.75-3.69). CONCLUSIONS AND RELEVANCE: An increasing number of midlife vascular risk factors was significantly associated with elevated amyloid SUVR; this association was not significant for late-life risk factors. These findings are consistent with a role of vascular disease in the development of Alzheimer disease.

A deletion polymorphism in the RIZ gene is associated with increased progression of imatinib treated chronic myeloid leukemia patients.

RIZ1 encodes a retinoblastoma (Rb)-interacting zinc finger protein, is commonly lost or expressed at reduced levels in cancer cells. The RIZ1 gene locus commonly undergoes LOH in many cancers. Here, we analyzed Proline insertion-deletion polymorphism at amino acid position 704 in the RIZ1 gene and its association with CML. The RIZ1 pro-704 LOH genotypes were determined by AS-PCR in 100 CML patients among which 50 were in CP-CML, 25 in AP-CML, and 25 in BC-CML. Pro704 ins/del polymorphism (LOH) was detected in 27% CML patients. Proline ins-ins homozygosity, del-del homozygosity and ins-del heterozygosity was detected in 9%, 18%, and 73% CML patients compared with 3%, 3%, and 94% in healthy controls, respectively (p < .0003). A four-fold increased risk was found to be associated del-del genotype. We found a statistically significant association between RIZ1 LOH and stage (p > .01) and hematological resistance (p > .001). However, there were no correlations found with other clinical parameters like age, gender, thrombocytopia, type of BCR-ABL, and molecular response. Our findings suggest that proline 704 del-del homozygosity phenotype can play an important role in progression of CML.

Side scatter versus CD45 flow cytometric plot can distinguish acute leukaemia subtypes.

BACKGROUND & OBJECTIVES: Flow cytometry is an important tool to diagnose acute leukaemia. Attempts are being made to find the minimal number of antibodies for correctly diagnosing acute leukaemia subtypes. The present study was designed to evaluate the analysis of side scatter (SSC) versus CD45 flow dot plot to distinguish acute myeloid leukaemia (AML) from acute lymphoblastic leukaemia (ALL), with minimal immunological markers. METHODS: One hundred consecutive cases of acute leukaemia were evaluated for blast cluster on SSC versus CD45 plots. The parameters studied included visual shape, CD45 and side scatter expression, continuity with residual granulocytes/lymphocytes/monocytes and ratio of maximum width to maximum height (w/h). The final diagnosis of ALL and AML and their subtypes was made by morphology, cytochemistry and immunophenotyping. Two sample Wilcoxon rank-sum (Mann Whitney) test and Kruskal-Wallis equality-of-populations rank tests were applied to elucidate the significance of the above ratios of blast cluster for diagnosis of ALL, AML and their subtypes. Receiver operating characteristic (ROC) curves were generated and the optimal cut-offs of the w/h ratio to distinguish between ALL and AML determined. RESULTS: Of the 100 cases, 57 of ALL and 43 cases of AML were diagnosed. The median w/h ratio of blast population was 3.8 for ALL and 1 for AML (P<0.001). ROC had area under curve of 0.9772.The optimal cut-off of the w/h ratio for distinction of ALL from AML was found to be 1.6. INTERPRETATION & CONCLUSIONS: Our findings suggest that if w/h ratio on SSC versus CD45 plot is less than 1.6, AML may be considered, and if it is more than 1.6, ALL may be diagnosed. Using morphometric analysis of the blast cluster on SSC versus CD45, it was possible to distinguish between ALL and AML, and their subtypes.

A Study of Haemostatic Parameters in Patients of Chronic Myeloid Leukaemia.

INTRODUCTION: Chronic Myeloid Leukaemia (CML) is characterized by derangement of various components of the haemostatic system resulting in thrombo-haemorrhagic complications. Although less common than other myeloproliferative neoplasms, derangement of various components of the haemostatic system is observed in CML. Haemostatic abnormalities have been described in relation to hyperleucostasis and drugs used to treat CML. However, the correlation between haemostatic derangements and phase of CML is unclear in the literature. AIM: The purpose of this cross-sectional study was to assay various haemostatic parameters in patients of CML receiving Imatinib and to determine any correlation between them and phases of disease as well as the status of remission. MATERIALS AND METHODS: The study included 30 patients with CML (17 males, 13 females, mean age of 35.53 ± 8.92 years) receiving imatinib mesylate. Haemostatic parameters including platelet counts, Prothrombin Time (PT), activated Partial Thromboplastin Time (APTT), fibrinogen, D-dimers and Factor VIII levels were assayed for all patients using standard methods. Bcr-abl gene product (quantitative) was determined on the peripheral blood by reverse transcriptase polymerase chain reaction (RT-PCR). Patients were grouped into phases of disease (chronic, accelerated and blast) and their response to imatinib was determined in the form of remission (clinical, haematological and molecular). Correlations were drawn between them using spearman's coefficient. RESULTS: A significant positive correlation was found between PT (p=0.002), fibrinogen (p=0.011), D-dimers (p=0.050), Factor VIII levels (p=0.006) with the phase of CML and a significant negative correlation was observed between PT (p=0.003, 0.006), fibrinogen (p=0.010, 0.005), D-dimers (p=0.035, 0.017), Factor VIII levels (p=0.005, 0.001) and clinical and haematological remission respectively. No significant correlation of platelet counts and APTT was seen with the phase of CML or remission status. CONCLUSION: Haemostatic system is significantly disturbed in CML and correlate positively with the progression of the disease. Imatinib treatment leads to improvement in some of these parameters.

Tuberculosis as an Etiological Factor in Liver Abscess in Adults.

Background. Tuberculosis of the liver without active pulmonary or miliary tuberculosis is considered as an uncommon diagnosis. The aim of the present study was to determine the etiological role of tuberculosis in adult patients presenting with features of liver abscess. Methods. A total of 40 patients with liver abscess were included in the study. The liver abscess aspirate was subjected to microscopy, culture, and polymerase chain reaction to determine the role of tuberculosis as an etiological factor in liver abscess. Results. Of the 40 patients enrolled, 25% (10/40) were diagnosed with having tubercular liver abscess. In a total of 40 specimens, 2.5% (1/40) were positive for acid fast bacilli by Ziehl-Neelsen method, while 10% (4/40) were positive for M. tuberculosis by culture using BACTEC 460 and the yield increased to 25% (10/40) by polymerase chain reaction for M. tuberculosis. Conclusion. 25% of the patients presenting with liver abscess had tubercular etiology without features of active pulmonary or miliary tuberculosis. Liver can act as the primary site of involvement in the absence of activity elsewhere in the body. Tuberculosis should be considered as an important differential diagnosis of liver abscess irrespective of evidence of active tuberculosis elsewhere in the body.

Primary Hodgkin's Lymphoma of the Sternum: Report of a Case and Review of the Literature.

Sternal masses present a unique diagnostic challenge in clinical practice. A wide array of differential diagnosis of a sternal mass includes osteomyelitis, tuberculosis, eosinophilic granuloma, sarcoma and lymphoma (usually Non-Hodgkin's) amongst others. Sternum is a rare site of Hodgkin's lymphoma and is usually misdiagnosed as tuberculosis or eosinophilic granuloma on routine histopathology. This delayed diagnosis culminates in death of patients. We report a 30-year-old lady who presented with swelling in upper part of chest wall since 1 month. Past history was significant for a similar swelling 2 years back, which was diagnosed as hodgkin's lymphoma and treated with 4 cycles of chemotherapy at another centre (which led to resolution of the swelling). Examination revealed a 6x6.5cm firm swelling originating from the upper part of sternum. There was no lymphadenopathy or organomegaly. Histopathological examination (with immunohistochemistry) of the trucut biopsy from the swelling confirmed the diagnosis of Hodgkin's lymphoma (nodular sclerosis). Patient was diagnosed as a late relapse of primary sternal Hodgkin's lymphoma (stage IBE) and was administered 4 cycles of ABVD followed by local radiotherapy to the involved site which led to complete resolution of the disease as assessed by PET scan. We present this unusual case of primary sternal Hodgkin's lymphoma. Rarity of this entity, with diagnostic challenges encountered and treatment options available are highlighted in the current report. A pubmed search revealed 18 cases of sternal involvement in Hodgkin's lymphoma which have been tabulated.