Anaemia of chronic disease among pulmonary tuberculosis patients is associated with inflammatory marker at the start of intensive phase.

Background: Tuberculosis (TB) disrupts iron balance through systemic inflammation. Pulmonary tuberculosis (PTB) is linked to diverse anaemia types, necessitating intricate haematological and biochemical assessments for diagnosis. This study aims to describe the prevalence of anaemia of chronic disease (ACD), iron deficiency anaemia (IDA) among PTB patients and factors associated with these types of anaemia. Methods: A cross-sectional analysis was conducted from community-based cohort study involving sputum-positive PTB patients from 2018 to 2020 in urban Puducherry. Participants were enrolled from 10 primary health centres within 2 weeks of initiating anti-tubercular treatment (ATT). Blood samples were collected for assessing haematological and biochemical parameters. The sTfR/log ferritin ratio was used to distinguish between ACD and IDA. Data were captured using Epicollect5 and analysed using STATA V14. Result: Of the 176 PTB patients included, 63.07% (111/176) had anaemia, with ACD being the predominant type (84.6%, 94/111). The C-reactive protein (CRP) levels were higher among the anaemic group [40.77 (16.66-58.51) mg/dl vs 24.65 (14.23-47.26) mg/dl] and higher among the ACD as compared to IDA [46.9 (22.3-61.2) vs 20.8 (13.0-39.1) mg/dl]. Undernourished [adjusted prevalence ratio (APR) =3.43; confidence interval (CI): 1.21-9.69] and patients having low risk of dependence on tobacco [APR = 1.52; CI: 1.10-2.11] had higher risk of ACD. Female patients had higher risk of IDA [APR = 4.95, P < 0.01]. Conclusion: The largest proportion of the PTB participants with anaemia had ACD. Acute-phase reactant and inflammatory marker are increased among newly diagnosed new sputum smear-positive (NSP) PTB participants at the start of ATT. Addressing inflammation is needed for combating anaemia in PTB patients.

Myeloid sarcoma: Experience from a tertiary care center in southern India - A series of eight unusual cases.

BACKGROUND: Myeloid sarcoma (MS) is a tumor mass comprising myeloid blasts with or without maturation occurring in any site other than bone marrow. It is a rare and distinct clinical presentation of myeloid neoplasm. MATERIALS AND METHODS: This is a retrospective study over 7 years (2015-2022) comprising a series of eight cases, which includes clinical details, morphology, immunohistochemistry (IHC) markers, cytogenetics, and molecular details. RESULTS: These cases showed up as an isolated MS (3/8), as an initial clinical presentation in acute myeloid leukemia (1/8), as acute myeloid leukemia (1/8), as a disease progression in primary myelofibrosis (1/8), as chronic myeloid leukemia (1/8), and as BCR-ABL-negative myelodysplastic syndrome/myeloproliferative neoplasm (1/8). One of the three isolated MS was incorrectly identified as having Ewing's sarcoma. One case each presented at the cervical lymph node, mediastinum, skin, sacral soft tissue, maxillary sinus, and perinephric fat, and two cases presented at the hard palate. CONCLUSION: Four of the cases in our study were clinically thought of as lymphoma/sarcoma, which was a major diagnostic challenge. All but one case succumbed to their disease. Without adequate clinical history and appropriate use of ancillary techniques such as IHC in tissue biopsies, flow cytometry, cytogenetics, and molecular studies, these cases have a high chance of being misdiagnosed as non-Hodgkin lymphoma, small round blue cell tumor, or undifferentiated carcinomas, which can complicate patient management and prognosis.

Flow Cytometric Assessment of CD26-Positive Leukemic Stem Cells: A Rapid and Valuable Tool in the Diagnosis and Follow-Up of Chronic Myeloid Leukemia.

Context Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm. Recent studies have suggested that CD26-positive leukemic stem cells (LSCs) circulating in peripheral blood are specific for CML. Objective This study was undertaken to determine the proportion of CD26-positive LSCs at diagnosis and its change during tyrosine kinase inhibitor therapy. Design This prospective study was conducted on 43 cases of CML at diagnosis. For flow cytometry, peripheral blood cells were stained with CD45, CD34, CD38, CD3, and CD26. A sequential gating strategy with CD45/SSC (side scatter), CD34/SSC, and CD34/CD38 was applied to identify CD45+/34+/38- populations, from which CD26-positive stem cells were identified and compared with controls. Data analysis was done with Kaluza software. Results All patients diagnosed with CML were detected with CD26-positive LSCs. The median percentage of CD26-positive CML LSCs was 0.02 with a range of 0.001 to 1.77. None of the control samples showed CD26 positivity. The percentage and absolute count of CD26-positive CML LSCs were reduced after six months of tyrosine kinase therapy in patients with complete hematological remission. Conclusion Flow cytometric analysis of circulating CD26-positive CML LSCs is a non-invasive, rapid, and useful tool in the diagnosis and follow-up of CML.

Longitudinal Echocardiographic Follow-Up of a Pediatric Multisystem Inflammatory Syndrome Cohort.

OBJECTIVE: Significant involvement of the cardiovascular system is known in multisystem inflammatory syndrome in children (MIS-C). This study aimed to examine the recovery of affected cardiovascular parameters over a medium-term follow-up. METHODS: A cohort of 69 children was studied prospectively. Assessments of left ventricular (LV) function and coronary artery abnormalities (CAA) were conducted at admission, 1.5 months, and 3 months. Coronavirus Disease 2019 (COVID-19) antibody titers were assessed at these three time points. Echocardiographic and antibody parameters (rising/decreasing) were analyzed for correlation. Outcomes were assessed using logistic regression. RESULTS: At admission, among the 78.2% of patients who were tested, 88.9% tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A quarter of the patients had pericardial effusion, and half had valvulitis. Decreased ejection fraction, global circumferential strain (GCS), and global longitudinal strain (GLS) were seen in 54.4%, 68.6%, and 35.8% of patients, respectively. CAAs were observed in 27.78% of patients. Systolic dysfunction was significantly associated with older age. During follow-up, severe LV dysfunction normalized within 6-7 weeks, while mild to moderate dysfunction reached normalcy by two weeks. Both GCS and GLS reached normalcy within a median of two weeks. Diastolic parameters recovered by six weeks. Most small and moderate coronary aneurysms resolved, but a giant aneurysm in an infant remained large even after 15 months. Trends in antibodies and ejection fraction (EF) at three months were significantly correlated. Admission EF, GLS (at 6 weeks) and deceleration time (at 3 months) were significantly associated with intensive care unit (ICU) admission. The median segmental strain of the cohort remained low in certain segments at three months. CONCLUSION: Smaller CAAs resolve, whereas giant CAAs persist. EF and GLS are important predictors of Pediatric Intensive Care Unit (PICU) stay. The residual impairment of median segmental strain and persistent diastolic dysfunction at three months indicate the need for long-term follow-up.

Predictors of Change in the Anemia Status Among Pulmonary Tuberculosis Patients Following Anti-tuberculosis Treatment in Puducherry, India.

Background Pulmonary tuberculosis (PTB) is commonly associated with reversible peripheral blood abnormalities. The evolution of tuberculosis (TB)-associated anemia with anti-tuberculosis treatment (ATT) has not been well elucidated. This study aimed to compare the hematological profiles at the start and end of the ATT among new sputum smear-positive (NSP) PTB patients in Puducherry, India. Methods A prospective cohort study was conducted in the 10 urban primary health centers of Puducherry from 2017 to 2020. All the NSP PTB participants aged ≥18 years registered under the National Tuberculosis Elimination Program (NTEP) were contacted within two weeks of the start of the ATT. All eligible participants were enrolled, and they were followed up till the end of ATT (180 days). Hematological profiles and anthropometric measurements were compared at the start and end of the ATT. Binomial logistic regression analysis was used to assess the predictors of changes in the anemia status at the start and end of the ATT. Results Out of 176 NSP PTB participants, 145 were followed up after treatment. Initially, 63% (111/176) patients had anemia, which decreased to 44% (64/145) by the end of treatment. The risk factors for a negative change in hemoglobin levels were female gender, below poverty level, underweight, and reduced iron intake. The adjusted risk ratios (ARRs) were 1.53 (1.24-1.88), 1.18 (1.01-1.38), 1.29 (1.02-1.64), and 1.26 (1.05-1.51),respectively. Conclusion ATT may lead to the resolution of TB-associated anemia. Moreover, female gender, possession of a red ration card, being underweight, and reduced iron intake were identified as risk factors for negative changes in hemoglobin levels during treatment.

A case series of therapy-related leukemias: A deadly ricochet.

Therapy-related leukemias(t-leukemia) are late complications arising from chemotherapy and radiotherapy. t-leukemia have a poor prognosis and are more difficult to treat compared to de novo leukemias. The authors present three cases of t-leukemia seen in our hospital in a three year period and discuss new updates concerning the treatment of t-leukemia.

Clinical profile and outcomes of multisystem inflammatory syndrome in children (MIS-C): Hospital-based prospective observational study from a tertiary care hospital in South India.

AIM: To study the clinical profile and outcomes in children with multisystem inflammatory syndrome in children (MIS-C). METHODS: Children aged 1 month to 15 years presenting with MIS-C (May 2020 to November 2021) were enrolled. Clinical, laboratory, echocardiography parameters and outcomes were analysed. RESULTS: Eighty-one children (median age 60 months (24-100)) were enrolled. Median duration of fever was 5 days (3-7). Twenty-nine (35.8%) had shock (severe MIS-C) including 23 (28.3%) requiring inotropes (median duration = 25 h (7.5-33)). Ten required mechanical ventilation, 12 had acute kidney injury and 1 child died. Left ventricular (LV) dysfunction was seen in 38 (46.9%), 16 (19.7%) had coronary artery abnormalities (CAA) and 13 (20%) had macrophage activation syndrome. Sixty-one (75.3%) were SARS CoV-2 positive (10 by RT-PCR and 51 by serology). Sixty-eight (83.9%) received immunomodulators. Younger age was significantly associated with CAA (P value = 0.05). Older age, LV dysfunction, SARS CoV-2 positivity, low platelet count and elevated serum ferritin were significantly associated with severe MIS-C (univariate analysis). Younger age was an independent predictor of CAA (P = 0.05); older age (P = 0.043) and low platelet count (P = 0.032) were independent predictors of severe MIS-C (multivariate logistic regression analysis). CONCLUSION: Our patients had diverse clinical manifestations with a good outcome. Younger age was significantly associated with CAA. Older age, LV dysfunction, low platelet count and elevated serum ferritin were significantly associated with severe MIS-C. Younger age is an independent predictor of CAA. Older age and low platelet count are independent predictors of severe MIS-C.

Effects of Cleistanthus collinus on the reproductive system of male Wistar rats.

OBJECTIVE: Plants are widely used in the traditional system of medicine and many of them can adversely affect the reproductive system. Cleistanthus collinus is a plant containing many active phytochemicals, which have the potential to be developed as a drug. The present study was aimed to evaluate the effects of an aqueous extract of C. collinus on the male reproductive system. METHODS: Male Wistar rats were treated with different doses of C. collinus (200 and 400 mg/kg, orally), or with saline for 28 days and its effect on the reproductive system was assessed. Cyclophosphamide (100 mg/kg, weekly, i.p), a well-known reproductive toxicant, was used as a positive control. RESULTS: There was a significant reduction in sperm count and motility with C. collinus treatment, along with the destruction of primary spermatocytes, spermatids and reduced thickness of the basal layer. The LH, FSH and testosterone levels were reduced significantly. A reduction in the area of seminiferous tubules indicates the destruction of germ cells and Sertoli cells. C. collinus treatment increased the oxidative stress, evidenced by elevated malondialdehyde levels along with a reduction in catalase and GSH activities. The expression of BAX, BCL-2 and p53 was observed in spermatocytes, indicating an increase in apoptosis. CONCLUSIONS: C. collinus can produce male reproductive toxicity, which may be mediated through alterations in hormonal levels, which in turn interferes with spermatogenesis. It may increase the expression of apoptotic factors and deplete protective antioxidant enzymes in the testis.

Comparison Between Manual and Automated Methods of Counting Reticulocytes and the Effect of Sample Storage on Reticulocyte Count: A Cross-Sectional Study from Southern India.

Reticulocyte count is a basic test in hematology. This study was done to compare manual and automated methods and to study the effect of sample storage on reticulocyte count. Analyses of samples (n = 86) were done at 2, 6, 24 and 48 h after blood collection. Manual counting was done from both freshly prepared slide and stored slide by microscopy on new methylene blue stained smears. Automated enumeration was on Sysmex XT-2000i analyser (Ret search II). The values of immature reticulocyte fraction (IRF) and low fluorescence reticulocytes (LFR) were also recorded. Comparison between two methods was done by Spearman's correlation and Mann-Whitney test. Effect of storage was analysed by repeated measures ANOVA. There was strong positive correlation between both manual and automated methods at 2, 6, 24 and 48 h. The differences between the manual and automated methods were not significant at 2, 6 and 24 h (p 0.975, 0.967 and 0.227). The difference between the freshly prepared slide and stored slide were significant at 6, 24 and 48 h (p 0.015, 0.004 and 0.001). The change in reticulocyte count with time, decrease in IRF and increase in LFR were not significant up to 6 h but were significant at 24 and 48 h after blood collection. Both the methods were accurate and correlated well with each other. Freshly prepared smears for manual counting were better than counting on stored slide. Up to 6 h after blood collection results obtained by both methods are acceptable.

Utility of International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT) in Patients with Inherited Bleeding Disorders: A Cross-Sectional Study from Southern India.

The International Society on Thrombosis and Hemostasis bleeding assessment tool (ISTH-BAT) was developed to record bleeding symptoms and aid in patient diagnosis. This study was done to investigate the utility of ISTH-BAT in patients suspected to have inherited bleeding disorders. This cross-sectional study was conducted in a tertiary care hospital in Southern India over 3 and 1/2 years. A trained investigator administered the ISTH-BAT questionnaire to 432 patients undergoing evaluation for inherited bleeding disorder prior to routine coagulation screening and confirmatory tests and to 131 healthy volunteers as controls. Among patients, 42(9.7%) had primary hemostatic defect, 150(34.7%) had secondary hemostatic defects and 229(53%) had normal screening coagulogram with mean bleeding scores (BS) being 5.9, 6.9, and 4.2 respectively and the proportion of patients with abnormal BS being 69%, 88.7% and 59.4% respectively; the latter qualifying as unknown hemostatic defect. 11(2.5%) with acquired hemostatic defect on workup were excluded. The mean BS was 1.52 among healthy volunteers. Common bleeding patterns were epistaxis (73.8%), cutaneous bleeding (52.4%), hematuria (54.8%), menorrhagia (50%) in primary hemostatic defect; cutaneous bleeding (72%), muscle hematoma (58.7%), hemarthrosis (46.7%), menorrhagia (58.7%) in secondary hemostatic defects and epistaxis (45.9%), cutaneous bleeding (62.4%), menorrhagia (30.7%) in normal screening coagulogram group. Grade of bleeding was mostly 2 and sometimes 4 in primary, 2-4 in secondary and 1-2 in normal screening coagulogram group. ISTH-BAT is a valuable tool to record lifelong bleeding history. The pattern and score give clues regarding the nature and severity of the bleeding disorder.

Extramedullary early T-cell lymphoblastic crisis in a young pregnant chronic myeloid leukemia patient: Diagnosis with fine-needle aspiration cytology and flow cytometry.

Chronic myeloid leukemia (CML) most commonly presents in chronic phase. Blast crisis in CML is usually of myeloid phenotype, whereas among lymphoid lineage, B-cell lymphoblastic crisis is common. T lymphoblastic crisis is rare with near early T-cell precursor (ETP) immunophenotype being exceedingly rare and very little is known about its characteristics, treatment, and prognosis. Blast crisis can occur in extramedullary sites with lymph node being the most common site. CML is also less investigated and studied in pregnancy as it is considered a disease of older adults. We report a rare case of CML presenting in extramedullary site (lymph node) as extramedullary T-cell lymphoblastic crisis of near ETP immunophenotype in a young pregnant female, which was diagnosed on fine-needle aspiration cytology in combination with flow cytometry.

Clinicopathological Profile of Paraprotein-Associated Kidney Disease in Monoclonal Gammopathies: An Observational Study.

Background Renal involvement in monoclonal gammopathies presents with different clinico-morphological patterns and can manifest at the onset or the late phase of hematological disease, or after chemotherapy. The spectrum is ever-expanding with advancements in diagnostic methods. Renal biopsy is needed for accurate diagnosis, as each of these patterns carries therapeutic and prognostic implications. Methods A total of 41 cases of monoclonal gammopathies were included in the study. Clinical, biochemical, and hematological details were obtained, and pathological variables were observed. Patients were followed till the maximum possible period, and treatment history and follow-up creatinine details were collected. Results The spectrum of renal biopsy lesions observed included light chain cast nephropathy (LCCN) n=19, amyloidosis n=11, monoclonal immunoglobulin deposition disease (MIDD) n=6, and proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID) n=5; 10 of these cases can be categorized as monoclonal gammopathy of renal significance (MGRS). Acute kidney injury (AKI) (41%) is the predominant clinical presentation in general whereas the majority of amyloidosis cases presented with nephrotic and sub-nephrotic proteinuria. LCCN cases had high serum creatinine and calcium, positivity for M-spike, as well as a high FLC ratio, compared to the other types. Around 100% of LCCN and MIDD patients had myeloma and 100% of PGNMID cases had normal marrow. Conclusion More than three-fourths of patients were diagnosed with monoclonal gammopathies with biochemical and hematological workups after an initial kidney biopsy. The clinicopathological profile of these patients had a broad spectrum but there were still some consistent findings within the different types. A subgroup of patients (MGRS) had undetectable serum paraproteins but had monoclonal immunoglobulin deposition in the kidney.

Myeloma Cast Nephropathy an Unusual Association with HIV Infection Presenting with Renal Dysfunction.

Human immunodeficiency virus (HIV)-associated renal disease is a pan-nephropathy, causing glomerular, tubular, and interstitial changes. The common lesion is the collapsing variant of focal segmental glomerulosclerosis. Multiple myeloma presenting as light chain cast nephropathy in an HIV-positive patient is very rare. A 45-year-old female retropositive patient presented with one episode of hematuria. Kidney biopsy was performed with a clinical diagnosis of acute interstitial nephritis (AIN). Biopsy showed unremarkable glomeruli. Tubules were dilated and showed a few periodic acid-Schiff (PAS) positive and many PAS-negative fractured casts surrounded by histiocytic reaction. Immunofluorescence and immunohistochemistry (IHC) showed lambda restriction by the casts. Bone marrow aspirate showed an increase in plasma cells, and the biopsy showed nodular aggregates of atypical plasma cells, which showed lambda restriction by IHC. PAS-negative fractured tubular casts are known to be associated with HIV-related nephropathy and need detailed hematological workup to rule out an associated plasma cell dyscrasia.

Clinico-Pathologic Profile and Treatment Outcomes of Patients with Diffuse Large B Cell Lymphoma Based on Cell of Origin Classification.

Diffuse large B cell lymphoma (DLBCLs) constitute 40% of all non-Hodgkin lymphoma and it represent a heterogeneous group of neoplasms rather than a single clinicopathological entity. We analysed the outcomes and clinical features based on the cell of origin in a series of patients with DLBCL from our institute. Medical case records of all newly diagnosed DLBCL treated in our institute from January 2015 to July 2017 were analysed for this study. Cell of origin classification was based on immunohistochemistry using Hans algorithm. Kaplan-Meier curves were used to determine survival. Ninety-five patients were diagnosed to have DLBCL subtype. Immunophenotypic subtyping was available for 71 patients. The median age at diagnosis was 56 years with no difference between Germinal centre B cell (GCB) and non-Germinal centre B cell (non-GCB) subtypes. Approximately 44% of patients had extra-nodal disease, stomach being the commonest site. Forty percent of patients had stage III/IV disease. Bulky disease and extra-nodal presentation was predominantly seen with non-GCB subtype (46% vs 20% and 36% vs 29% respectively). Rituximab was used in 75% of the patients with DLBCL. The 2-year disease-free survival was 70% versus 53% (p = 0.38) in GCB versus non-GCB subtype. This is one of the few data on DLBCL patients reported from India which has described outcomes based on the cell of origin. The disease-free survival in our country appears to be superior in GCB subtype which needs to be confirmed in a larger subset of patients.

Indian Society of Hematology and Blood Transfusion (ISHBT) Consensus Document on Hematological Practice During COVID-19 Pandemic.

The SARS-CoV-2 (COVID-19) pandemic is a worldwide public health emergency with widespread impact on health care delivery. Unforeseen challenges have been noted during administration of usual haematology care in these unusual COVID-19 times. Medical services have been overstretched and frontline health workers have borne the brunt of COVID-19 pandemic. Movement restrictions during lockdown prevented large sections of population from accessing health care, blood banks from holding blood drives, and disrupted delivery of diagnostic hematology services. The disruption in hematology care due to COVID-19 pandemic in India has been disproportionately higher compared to other subspecialities as hematology practice in India remains restricted to major cities. In this review we chronicle the challenges encountered in caring for hematology patients during the COVID-19 pandemic in India and put forth recommendations for minimizing their impact on provision of hematology care with special emphasis on hematology practice in lower and middle income countries (LMICs).