Comprehensive insights into oral squamous cell carcinoma: Diagnosis, pathogenesis, and therapeutic advances.

Oral squamous cell carcinoma (OSCC) is considered the most common type of head and neck squamous cell carcinoma (HNSCC) as it holds 90 % of HNSCC cases that arise from multiple locations in the oral cavity. The last three decades witnessed little progress in the diagnosis and treatment of OSCC the aggressive tumor. However, in-depth knowledge about OSCC's pathogenesis, staging & grading, hallmarks, and causative factors is a prime requirement in advanced diagnosis and treatment for OSCC patients. Therefore present review was intended to comprehend the OSCCs' prevalence, staging & grading, molecular pathogenesis including premalignant stages, various hallmarks, etiology, diagnostic methods, treatment (including FDA-approved drugs with the mechanism of action and side effects), and theranostic agents. The current review updates that for a better understanding of OSCC progress tumor-promoting inflammation, sustained proliferative signaling, and growth-suppressive signals/apoptosis capacity evasion are the three most important hallmarks to be considered. This review suggests that among all the etiology factors the consumption of tobacco is the major contributor to the high incidence rate of OSCC. In OSCC diagnosis biopsy is considered the gold standard, however, toluidine blue staining is the easiest and non-invasive method with high accuracy. Although there are various therapeutic agents available for cancer treatment, however, a few only are approved by the FDA specifically for OSCC treatment. The present review recommends that among all available OSCC treatments, the antibody-based CAR-NK is a promising therapeutic approach for future cancer treatment. Presently review also suggests that theranostics have boosted the advancement of cancer diagnosis and treatment, however, additional work is required to refine the role of theranostics in combination with different modalities in cancer treatment.

Targeting the Wnt/ß-catenin cascade in osteosarcoma: The potential of ncRNAs as biomarkers and therapeutics.

Osteosarcoma (OS) is a bone cancer which stems from several sources and presents with diverse clinical features, making evaluation and treatment difficult. Chemotherapy tolerance and restricted treatment regimens hinder progress in survival rates, requiring new and creative therapeutic strategies. The Wnt/ß-catenin system has been recognised as an essential driver of OS development, providing potential avenues for therapy. Non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), are essential in modulating the Wnt/ß-catenin cascade in OS. MiRNAs control the system by targeting vital elements, while lncRNAs and circRNAs interact with system genes, impacting OS growth and advancement. This paper thoroughly analyses the intricate interplay between ncRNAs and the Wnt/ß-catenin cascade in OS. We examine how uncontrolled levels of miRNAs, lncRNAs, and circRNAs lead to an abnormal Wnt/ß-catenin network, which elevates the development, spread, and susceptibility to the treatment of OS. We emphasise the potential of ncRNAs as diagnostic indicators and avenues for treatment in OS care. The review offers valuable insights for academics and clinicians studying OS aetiology and creating new treatment techniques for the ncRNA-Wnt/ß-catenin cascade. Utilising the oversight roles of ncRNAs in the Wnt/ß-catenin system shows potential for enhancing the outcomes of patients and progressing precision medicine in OS therapy.

Prevalence of High and Moderate Risk of Liver Fibrosis Among Patients With Diabetes at a Noncommunicable Diseases (NCD) Clinic in a Primary Healthcare Center in Northern India.

Background Diabetes is a known entity that contributes to increased incidence and progress of liver fibrosis. Despite the integration of nonalcoholic fatty liver disease (NAFLD) into the NP-NCD program (National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases, and Stroke [NPCDCS]), screening individuals in primary healthcare settings for liver fibrosis remains uncommon. The objective of this study was to determine the prevalence of the risk of liver fibrosis in individuals with diabetes. Methodology The secondary data analysis was conducted among patients with diabetes attending the noncommunicable diseases (NCD) clinic at the Primary Health Center (PHC) Najafgarh, Delhi, from January 2023 to June 2023. We used the Fibrosis-4 (FIB-4) score to assess the risk of liver fibrosis. The data analysis was carried out using Stata 17.0 software (StataCorp, College Station, TX). Results Out of 394 individuals screened, 158 (39.5%) were male and 236 (60.5%) were female. Among the study participants, 64.9% (95% confidence interval [CI] 60.0%-69.7%) were of low risk, 30.5% (95% CI 25.9%-35.3%) were of intermediate risk, and 4.6% (95% CI 2.7%-7.1%) were of high risk of developing liver fibrosis based on FIB-4 scoring. The increased risk was associated with increased age, duration of diabetes, and dyslipidemia. Conclusions The prevalence of high risk of liver fibrosis among patients with diabetes was 4.6% (95% CI 2.7%-7.1%), whereas an intermediate risk of developing liver fibrosis was observed in 30.5%. The study advocates integrating these screening tools into primary healthcare settings, alleviating the strain on larger healthcare facilities. It also underscores the importance of early detection and management of liver fibrosis in patients with diabetes.

Utility of bone marrow examination in retinoblastoma and their correlation with hematological features.

Retinoblastoma makes up about 3% of all childhood malignancies. The frequency of metastatic retinoblastoma ranges from 4.8 to 11%. Assessing the bone marrow status of newly diagnosed patients is crucial because of the advantages of autologous bone marrow transplants for high-risk patients. This study aimed to determine the utility of bone marrow examination in cases of retinoblastoma and its correlation with hematological findings. This retrospective study was conducted at the Department of Pathology, King George's Medical University, Lucknow, India. A total of 34 cases of retinoblastoma with bone marrow examination were included in the study. Bone marrow infiltration was present in 17.65% (6/34) cases of retinoblastoma. Bone marrow aspirate myelogram showed that marrow metastasis in retinoblastoma was significantly linked with a reduced percentage of total myeloid cells (p=0.001) and segmented cells (p=0.006). The present study demonstrated that 15% (3/20) of retinoblastoma patients previously classified as nonmetastatic before bone marrow examination (stages I to III based on histology, imaging, and bone scan) had bone marrow metastases following bone marrow examination and were upgraded to stage IV. To conclude, a diligent and exhaustive search for metastatic cells in bone marrow is advised if the myelogram shows a reduced percentage of total myeloid and segmented cells. All stage II and stage III cases of retinoblastoma must undergo bone marrow examination for early metastasis detection, as it may result in an upgrade to stage IV disease, impacting the prognosis and necessitating distinct treatment modalities.

Study of Hemato-morphological Features in Neuroblastoma Infiltrating Marrow.

Objective Neuroblastoma typically affects children within the first 5 years of life and accounts for 10% of all pediatric malignancies. Neuroblastoma at onset may manifest as a localized or metastatic illness. The aim of this study was to identify hematomorphological features in neuroblastoma infiltrating marrow as well as to ascertain the prevalence of bone marrow infiltration in neuroblastoma. Materials and Methods This retrospective study included newly diagnosed 79 cases of neuroblastoma, which were referred for bone marrow examination for the staging of the disease. Medical records were retrieved to acquire hematomorphological findings of peripheral blood and bone marrow smears. Statistical Package for Social Sciences, IBM Inc., USA, version 21.0 was used to analyze the data. Results The interquartile age range of neuroblastoma cases was 24.0 to 72.0 months (median = 48 months) with a male to female ratio of 2.7:1. Also, 55.6% (44/79) of cases in the study population showed evidence of marrow infiltration. The bone marrow infiltration was significantly linked to thrombocytopenia ( p = 0.043) and nucleated red blood cells ( p = 0.003) in peripheral blood. The bone marrow smears of cases with infiltration showed a significant shift to the left in the myeloid series ( p = 0.001) and an increased number of erythroid cells ( p = 0.001). Conclusion For neuroblastoma patients, a diligent, exhaustive search for infiltrating cells in bone marrow is advised if thrombocytopenia or nucleated red blood cells are identified on a peripheral blood smear and bone marrow smears showed myeloid left shift with an increased number of erythroid cells.

Severe COVID-19-associated hyperinflammatory syndrome versus classic hemophagocytic lymphohistiocytosis: similarities, differences, and the way forward.

The hyperinflammatory immune response in severe COVID-19 infection shares features with secondary hemophagocytic lymphohistiocytosis (sHLH) in the form of fever, cytopenia, elevated inflammatory markers, and high mortality. There are contrasting opinions regarding utility of HLH 2004 or HScore in the diagnosis of severe COVID-19-related hyperinflammatory syndrome (COVID-HIS). This was a retrospective study of 47 patients of severe COVID-19 infection, suspected to have COVID-HIS and 22 patients of sHLH to other illnesses, to evaluate the diagnostic utility and limitations of HLH 2004 and/or HScore in context to COVID-HIS and to also evaluate the utility of Temple criteria for predicting severity and outcome in COVID-HIS. Clinical findings, hematological, and biochemical parameters along with the predictor of mortality were compared between two groups. Only 6.4% (3/47) of cases fulfilled ≥5/8 HLH 2004 criteria and only 40.52% (19/47) of patients showed HScore >169 in COVID-HIS group. 65.9% (31/47) satisfied the Temple criteria in COVID-HIS as compared with 40.9% (9/22) in the non-COVID group (p = 0.04). Serum ferritin (p = 0.02), lactate dehydrogenase (p = 0.02), direct bilirubin (p = 0.02), and C-reactive protein (p = 0.03) were associated with mortality in COVID-HIS. Both HScore and HLH-2004 criteria perform poorly for identifying COVID-HIS. Presence of bone marrow hemophagocytosis may help to identify about one-third of COVID-HIS missed by the Temple Criteria.

T-cell dysfunction as a potential contributing factor in post-COVID-19 mucormycosis.

BACKGROUND: The second wave of COVID-19 in India was followed by large number of mucormycosis cases. Indiscriminate use of immunosuppressive drugs, underlying diseases such as diabetes, cancers, or autoimmune diseases was thought to be the cause. However, the mortality was not as high as that seen in non-COVID mucormycosis. OBJECTIVE: To study the detailed characteristics of T-cells for evaluating the underlying differences in the T-cell immune dysfunction in post-COVID and non-COVID mucor patients. MATERIAL AND METHOD: The study included histopathologically confirmed cases of mucor (13 post-COVID, 13 non-COVID) and 15 healthy individuals (HI). Expression of T-cell activation (CD44, HLADR, CD69, CD38) and exhaustion (CTLA, PD-1, LAG-3 and TIM-3) markers was evaluated by flow cytometry. RESULTS: All cases showed significant depletion of T-cells compared to HI. Both post-COVID and non-COVID groups showed increased activation and exhaustion as compared to HI. Non-COVID mucor group showed significant activation of CD4+ T cells for HLADR and CD38 (p = .025, p = .054) and marked T-cell exhaustion in form of expression of LAG-3 on both CD4+ T and CD8+ T cells in comparison with post-COVID patients (p = .011, p = .036). Additionally, co-expression of PD-1 & LAG-3 and LAG-3 & TIM-3 on CD8+ T cells was statistically significant in non-COVID mucor patients (p = .016, p = .027). CONCLUSION: Immunosuppression in non-COVID mucor showed pronounced exhaustion of T-cells in comparison to post-COVID mucor cases implicating T-cell immune dysfunction is much more severe in non-COVID mucor which are in a state of continuous activation followed by extreme exhaustion leading to poorer outcome.

Interleukin-6 and interleukin-8 levels in children with aplastic anemia and its correlation with disease severity and response to immunosuppressive therapy.

Background: Aplastic anemia (AA) is an uncommon condition characterized by pancytopenia and hypocellular bone marrow. Interleukin (IL)-6 and IL-8 have been shown to inhibit myelopoiesis and are major mediators of tissue damage. The primary goal of this study was to determine the IL-6 and IL-8 levels in children with AA, as well as their relationship to illness severity and immunosuppressive medication response. Materials and Methods: The IL-6 and IL-8 levels were tested in 50 children aged 3-18 years who had AA. As controls, 50 healthy age and sex matched individuals were used. A sandwich enzyme-linked immunosorbent assay kit (solid-phase) was used to measure IL-6 and IL-8 levels quantitatively. The concentrations of IL-6 and IL-8 in pg/mL were used to represent the results. Immunosuppressive medication was given to the patients in accordance with the British Committee for Standards in Haematology Guidelines 2009. Results: The patients' average age was 11.3 ± 3.7 years. Patients with AA had significantly higher IL-6 and IL-8 levels than controls (278.88 ± 216.03 vs. 4.51 ± 3.26; P < 0.001) and (120.28 ± 94.98 vs. 1.79 ± 0.78; P < 0.001), respectively. The IL-6 and IL-8 levels were also investigated with respect to AA severity, with statistically significant differences (P < 0.01) between different grading strata. Patients with very severe AA (VSAA) had the highest IL-6 levels (499.52 ± 66.19), followed by severe AA (SAA) (201.28 ± 157.77) and non-SAA (NSAA) (22.62 ± 14.63). For IL-8 levels, a similar trend (P < 0.01) was detected, with values of 209.81 ± 38.85, 92.12 ± 78.0, and 9.29 ± 10.68 for VSAA, SAA, and NSAA, respectively. After 6 months of immunosuppressive treatment (IST), mean levels of IL-6 and IL-8 in responders and nonresponders were again assessed. The mean IL-6 level in the responders' group (46.50 ± 45.41) was significantly lower, when compared to the nonresponders' group (145.76 ± 116.32) (P < 0.001). Similarly, the mean IL-8 level in the responder's group (33.57 ± 27.14) was significantly lower, compared to the nonresponder's group (97.49 ± 69.00) (P < 0.001). Conclusions: Children with AA had higher IL-6 and IL-8 levels than normal age- and sex-matched controls. Increased levels were linked to the severity of the condition, suggesting that IL may have a role in AA. IL levels can be monitored in AA patients during IST, which can assist in predicting response to IST.

Résumé Contexte: L'anémie aplastique (AA) est une affection peu fréquente caractérisée par une pancytopénie et une moelle osseuse hypocellulaire. Il a été démontré que l'interleukine (IL)-6 et l'IL-8 inhibent la myélopoïèse et sont des médiateurs majeurs des lésions tissulaires. L'objectif principal de cette étude était de déterminer les niveaux d'IL-6 et d'IL-8 chez les enfants atteints d'AA, ainsi que leur relation avec la gravité de la maladie et la réponse aux médicaments immunosuppresseurs. Matériel et méthodes: Les niveaux d'IL-6 et d'IL-8 ont été testés chez 50 enfants âgés de 3 à 18 ans atteints d'AA. 50 témoins sains appariés par l'âge et le sexe ont été utilisés. Un kit de dosage immuno-enzymatique en sandwich (phase solide) a été utilisé pour mesurer quantitativement les niveaux d'IL-6 et d'IL-8. de manière quantitative. Les concentrations d'IL-6 et d'IL-8 en pg/mL ont été utilisées pour représenter les résultats. Des médicaments immunosuppresseurs ont été administrés aux patients conformément aux directives 2009 du British Committee for Standards in Haematology. Résultats: L'âge moyen des patients était de 11,3 ± 3,7 ans. Les patients atteints d'AA présentaient des taux d'IL-6 et d'IL-8 significativement plus élevés que les témoins (278,88 ± 216,03 contre 4,51 ± 3,26 ; P < 0,001) et (120,28 ± 94,98 contre 1,79 ± 0,78 ; P < 0,001), respectivement. Les taux d'IL-6 et d'IL-8 ont également été étudiés en fonction de la gravité de l'AA, avec des différences statistiquement significatives (P < 0,01) entre les différentes strates de classement. Les patients présentant une AA très sévère (VSAA) avaient les taux d'IL-6 les plus élevés (499,52 ± 66,19), suivis par les patients atteints d'AA sévère (SAA) (201,28 ± 157,77) et les patients non-SAA (NSAA) (22,62 ± 14,63). Pour les niveaux d'IL-8, une tendance similaire (P < 0,01) a été détectée, avec des valeurs de 209,81 ± 38,85, 92,12 ± 78,0, et 9,29 ± 10,68 pour les VSAA, SAA et NSAA, respectivement. Après 6 mois de traitement immunosuppresseur traitement immunosuppresseur (IST), les niveaux moyens d'IL-6 et d'IL-8 chez les répondeurs et les non-répondeurs ont été à nouveau évalués. Le taux moyen d'IL-6 dans le groupe des répondeurs (46,50 ± 45,41) était significativement plus faible, par rapport au groupe des non-répondeurs (145,76 ± 116,32) (P < 0,001). De même, le niveau moyen d'IL-8 dans le groupe des répondeurs (33,57 ± 27,14) était significativement plus faible que dans le groupe des non-répondeurs (97,49 ± 69,00) (P < 0,001). Conclusions: Les enfants atteints d'AA présentaient des niveaux d'IL-6 et d'IL-8 plus élevés que les témoins normaux appariés selon l'âge et le sexe. L'augmentation des taux était liée à la gravité de l'affection, suggérant que l'IL pourrait jouer un rôle dans l'AA. Les niveaux d'IL peuvent être surveillés chez les patients atteints d'AA pendant l'IST, ce qui peut aider à prédire la réponse à l'IST. Mots-clés: Anémie aplastique, traitement immunosuppresseur, interleukine-6, interleukine-8.

Placental Growth Factor in First Trimester of Pregnancy for Prediction of Maternal and Perinatal Adverse Outcomes.

Purpose of the study: Placental growth factor (PLGF) is an angiogenic factor in pregnancy. To find out correlation of plasma levels of placental growth factor in first trimester of pregnancy in Indian women who develop maternal and perinatal adverse outcomes was the aim of the study. Methods: A prospective longitudinal noninterventional study was done in the department of Obstetrics and Gynecology after obtaining ethics approval. After enrolling patients in the first trimester (11 weeks to 13 weeks 6 days), a questionnaire was filled for demographic characteristics. Uterine artery doppler was done for every patient and blood sample (5 ml) was taken by venu puncture of median cubital vein. Serum levels of PLGF were measured by enzyme linked immunosorbent assay using Thermo Scientific Pierce Human PLGF kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA). Patients were followed for their whole antenatal period and delivery outcomes. Results: Incidence of preeclampsia in our study was 9.3% (15/161) and fetal growth restriction (FGR) was 19.8% (32/161). Neither BMI nor nulliparity was found to have statistically significant correlation with development of preeclampsia. However, history of preeclampsia was found to be significant risk factor for prediction of preeclampsia (p value < 0.04). Plasma levels of PLGF were significantly lower in preeclampsia and FGR group and this difference was statistically significant (p value < 0.04). 7.5% still born occurred in complicated group and 10% needed NNU/NICU admission in this group. Conclusion: Measuring PLGF levels in first trimester of pregnancy can help in prediction of preeclampsia and FGR.

Reed Sternberg-Like Cells in Non-Hodgkin Lymphoma: A Diagnostic Challenge.

Reed-Sternberg cells are distinguishing features of classical Hodgkin lymphoma. However, they are seen infrequently, in both B and T cells Non-Hodgkin lymphomas with a comparable morphology and immunophenotype. These cells are known as Reed-Sternberg-like cells. The characteristic background milieu of classical Hodgkin lymphoma is typically not present in Non-Hodgkin lymphomas, and Reed-Sternberg-like cells are typically present as dispersed cells or in tiny clusters. They are positive for CD30, show variable expression of B cell lineage markers and are negative for CD45/LCA in Non-Hodgkin lymphomas. Reed-Sternberg-like cells have phenotypes that are remarkably similar to those of conventional Reed-Sternberg cells. In this interesting case report, we discuss a case of disseminated B-cell Non-Hodgkin lymphoma with Reed-Sternberg-like cells that presented as a diagnostic challenge. It is essential to distinguish between classical Hodgkin lymphoma and Non-Hodgkin lymphomas due to distinct therapy protocols and prognosis. The presence of large CD30 positive Reed-Sternberg like cells may mimic Hodgkin's Lymphoma. However, monomorphic background population with CD20 positivity should always raise the suspicious of B-cell Non-Hodgkin lymphoma. Immunohistochemical detection of a panel of targets should always be applied to correctly diagnose these rare cases of B-cell Non-Hodgkin lymphoma with Reed-Sternberg like cells.

Hyperlipidemia and Platelet Parameters: Two Sides of the Same Coin.

INTRODUCTION:  Hyperlipidemia is a disorder in which lipid and cholesterol levels in the blood are elevated. Diabetes, coronary heart disease, obesity, and hypertension are commonly linked to hyperlipidemia. Despite this, hyperlipidemia is a widely neglected illness, owing to its asymptomatic nature, ignorance of aberrant lipid profiles on screening, and economic issues in poor countries such as India. Platelets have been shown to have a role in the thrombus consequences of atheromatous damage in hyperlipidemic individuals by initiating and propagating atherosclerotic plaques. Platelets with bigger diameters are thought to be more metabolically, enzymatically, and functionally agile than platelets with lower sizes. In steady-state operation, these bigger platelets release more thromboxane B2 than regular platelets. Platelets with bigger sizes are more hemostatically active and hence have a higher chance of forming a thrombus and thromboembolism. The aim of this study was to compare the values of key platelet parameters and platelet function in hyperlipidemic patients with normal age and sex-matched controls. MATERIAL AND METHODS:  A total of 100 individuals were included in this study, with 68 cases of hyperlipidemia and 32 controls having normal lipid profiles. Platelet volume indices (PVI) such as platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR), plateletcrit (PCT), and platelet function (platelet aggregation with adenosine diphosphate, ADP) were compared between hyperlipidemia patients and age sex-matched controls with normal lipid profiles. RESULTS:  The cases had a statistically significant higher mean MPV (10.55 ± 1.81), PDW (14.93 ± 2.82), and P-LCR (30.97 ± 11.74) compared to mean MPV (9.35 ± 1.85), PDW (13.10 ± 2.60), and P-LCR (25.13 ± 12.23) of controls (p-value < 0.05). No significant difference was observed between the study group and control group with respect to mean PC and PCT (p-value > 0.05). In this study, there was a statistically significant increase noted in platelet aggregation percentage in hyperlipidemic patients than in the control group (42.03 ± 25.28 vs 31.25 ± 15.11) (p-value < 0.05). CONCLUSION:  To conclude, platelet parameters are a significant, easy, and cost-effective method for predicting future acute episodes in hyperlipidemic patients that should be utilized more widely. To avoid vascular events, these individuals may require higher antiplatelet dosages and more rigorous hyperlipidemia therapy.

Serum Tumor Necrosis Factor-Alpha Levels in Acute Leukemia and Its Prognostic Significance.

Introduction Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that facilitates malignant cells in immune evasion, survival, and treatment resistance by generating a favorable milieu for them. It is shown to be ectopically produced by malignant/leukemic and immune cells in the tumor microenvironment, providing a tumor-supportive environment and playing an important part in the establishment and progression of malignant cells. It is linked to hyperleukocytosis, high blast count, and poor clinical outcomes in acute leukemia (AL). Considering the varied role and different expression patterns of tumor necrosis factor-alpha in acute leukemia and its clinical relevance, the present study was planned to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia and its correlation with disease outcome. The aim of this study was to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia at the time of diagnosis and after induction chemotherapy. Material and methods The study included cases classified as acute leukemia based on morphological examination, bone marrow analysis, and flow cytometry. In all patients with acute leukemia (n = 90) and controls (n = 10), the serum tumor necrosis factor-alpha level was measured using a Diaclone Human ELISA kit (Diaclone, Besancon, France) (solid phase sandwich ELISA) at diagnosis and after induction chemotherapy. Results Tumor necrosis factor-alpha levels were substantially higher in T-acute lymphoblastic leukemia (T-ALL) cases, followed by acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL), at the time of diagnosis, compared to the control. A significant reduction in serum tumor necrosis factor-alpha level was seen in patients with acute leukemia after induction phase chemotherapy (P < 0.05). Tumor necrosis factor-alpha levels were considerably reduced (P < 0.001) in the majority of acute leukemia cases after the induction phase, while high tumor necrosis factor-alpha levels were positively correlated with incomplete remission status in the remaining cases. Conclusion Tumor necrosis factor-alpha is involved in the progression of acute leukemia and its relapse. High levels of tumor necrosis factor-alpha are linked to leukocytosis, high blast counts, and worse survival in patients with acute leukemia. Monitoring of tumor necrosis factor-alpha may be helpful in patients with acute leukemia in view of available antitumor necrosis factor-alpha therapy.

Bleeding Versus Thrombotic Tendency in Young Children With Beta-Thalassemia Major.

Introduction Bleeding and thrombotic events are known to occur in beta-thalassemia major (BTM) patients and have been attributed to hepatic iron overload associated with multiple blood transfusions. We evaluated hemostatic parameters in children with BTM who had no previous history of bleeding or thrombotic episodes. Materials and Methods Hemostatic parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation, protein C and S, iron profile, and liver function tests were evaluated in 54 children (median age = 12 months, age range = 4-144 months) with BTM and 15 age and sex-matched controls. Results The mean PT and APTT of patients were significantly higher (P=0.016 and P <.001) than that of controls. Mean protein C, protein S activity and platelet aggregability with adenosine 5-diphosphate (ADP) as an agonist in patients were significantly lower (P <.001, P <.001 and P=0.007, respectively) than that in controls. Mean serum ferritin in BTM children was not significantly elevated to be associated with hepatic dysfunction. Conclusion Deranged hemostatic parameters indicative of bleeding and thrombotic tendencies are observed in BTM children from an early age and may not be solely due to hyperferritinemia-associated hepatic dysfunction. Despite the presence of deranged hemostatic parameters, a state of balance exists between bleeding and thrombosis, and an imbalance may lead to bleeding or thrombotic events at a later age.

A Cross Sectional Study on T Cells and Subsets in Chronic Lymphocytic Leukemia and their Association with Clinical Phenotype.

T cells in B chronic lymphocytic leukaemia (CLL) have been reported to show qualitative and quantitative alterations, thereby regulating the antitumor immune response. We evaluated the absolute count, percentages of T cells and subsets and their association with disease parameters in Indian patients. 45 treatment naïve CLL cases and 10 healthy controls were evaluated for CD3 + Tcells, CD4 + T cells, CD8 + T cells percentage by flowcytometry. The absolute counts were obtained by multiplication with absolute lymphocyte counts obtained on cell counter. The clinical characteristics (age, sex, Rai stage, B symptoms, CD38 expression) were analysed for any association with alteration of these cells (percentages, absolute counts, ratio with monoclonal B cell count) and CD4: CD8 ratio. The mean absolute count of CD3 + T cell, CD4 + T cell and CD8 + T cells was significantly higher (p < 0.05) in CLL patients as compared to healthy controls. CD4:CD8 ratio was variable (normal, increased and decreased). The mean CD8 + T cells count was higher in advanced disease stage, and CD38 positive cases (p > 0.05). Younger CLL patients (< 55 years) had greater increase in CD8 + T cells (p > 0.05). Significant alterations in T cells and their subsets were observed in CLL. A trend towards advanced stage, CD38 expression, presentation an early age was seen with increase in CD8 + T cell counts.

Hemophagocytic histiocytosis in severe SARS-CoV-2 infection: A bone marrow study.

INTRODUCTION: The clinical and laboratory features of severe COVID-19 infection overlap with those of hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory disorder often associated with several viral infections. The clinical syndrome of HLH encompasses fever, organomegaly, cytopenias, hyperferritinemia, hypertriglyceridemia, raised transaminases, hypofibrinogenemia, absent natural killer (NK) cell activity, increased soluble CD25 and hemophagocytic lymphohistiocytosis in bone marrow, spleen, and lymph nodes. METHODS: We analyzed clinicopathological and laboratory features of thirteen patients with severe COVID-19 infection suspected to have HLH and found to have hemophagocytic histiocytosis on bone marrow examination (BME). RESULTS: Five of thirteen (38.46%) patients fulfilled five of eight HLH 2004 criteria and/or had a H-score ≥169. Three (23.08%) satisfied four of eight and remainder five (38.46%) satisfied three of eight HLH 2004 criteria. Fever, raised serum ferritin (13/13, 100%), transaminases (9/13, 69.23%), triglycerides (4/13, 30.76%), cytopenias (5/13, 38.46%), hypofibrinogenemia (2/13, 15.38%), and organomegaly (1/13, 7.69%) were observed in our patients. BME showed hemophagocytic histiocytosis without lymphocytosis in all. Contrary to HLH, lymphocytopenia (11/13, 84.61%), leukocytosis (7/13, 53.84%), neutrophilia (7/13, 53.84%), and hyperfibrinogenemia (7/13, 53.84%) were observed. Serum CRP, LDH, and plasma D-dimer were elevated in all, while serum albumin was decreased in 12 of 13 (92.3%) patients. Five patients recovered with high-dose pulsed corticosteroid therapy. CONCLUSION: The immune response associated with severe COVID-19 infection is similar to HLH with few differences. HLH should be suspected in severe COVID-19 infection although all patients may not fulfill required HLH diagnostic criteria. BME should be done in suspected cases so that appropriate therapy may be initiated early.

Complicated case of COVID-19 disease with overlapping features of thrombotic thrombocytopenic purpura and haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis has been reported as an uncommon complication of severe COVID-19 disease while thrombotic thrombocytopenic purpura has been rarely reported. Here, we are reporting a 21-year-old man who developed a combination of these complications during the hospital stay in the post-COVID-19 recovery period. He presented with fever and bilateral COVID-19-related pneumonia requiring invasive ventilation. His hospital course was complicated by the development of pneumothorax, ventilator-associated pneumonia, thrombotic thrombocytopenic purpura and haemophagocytic lymphohistiocytosis. He received remdesivir, IVIG, steroid, fresh frozen plasma and supportive care but had a fatal outcome.

Non-compressive myelopathy: an unusual presentation of a patient with acute B lymphoblastic leukaemia.

A 21-year-old woman was admitted to the department of haematology with fever, generalised body ache and swelling of the feet. She also presented with band-like tightness over the abdomen and was unable to walk for the last 2 days. There was no history of trauma. She was diagnosed as a case of B-cell acute lymphoblastic leukaemia based on flow cytometry and bone marrow studies. MRI of the thoracolumbar spine revealed signal intensity alteration in the spinal cord from D1-2 to D5-6. Her serum vitamin B12 and folate levels were normal. Autoimmune workup including antinuclear antibody and viral serology, and reverse transcriptase PCR for herpes simplex virus, Epstein-Barr virus and cytomegalovirus were negative. Her cerebrospinal fluid was negative for malignant cells. She was started on Berlin-Frankfurt-Munster 95 protocol and her condition improved along with partial improvement in the power of her limbs at the time of discharge. The neurological diagnosis of non-compressive myelopathy due to myelitis was considered.

Effect of Imatinib on Bone Marrow Morphology and Angiogenesis in Chronic Myeloid Leukemia.

BACKGROUND AND OBJECTIVES: Chronic myeloid leukemia (CML) is characterized by hyperproliferation of myeloid precursors, increased fibrosis, and neoangiogenesis in the bone marrow. Imatinib inhibits BCR-ABL tyrosine kinase produced due to reciprocal translocation t(9;22) in neoplastic CML cells. It reduces hyperproliferation of myeloid precursors and has been found to affect bone marrow fibrosis and angiogenesis. This study was done to assess the effect of imatinib on bone marrow morphology and angiogenesis in CML. METHODS: 31 newly diagnosed CML patients were evaluated before and after 3 months of imatinib therapy. A marrow morphological response (MMR) score was used to assess marrow cytological and histological features including grade of fibrosis. Mean microvessel density (MVD) was also assessed. Hematological parameters and BCR-ABL transcript levels were assessed in the peripheral blood. RESULTS: 86.21% of patients showed decrease in marrow cellularity with normalization of M:E ratio. 72.42% of patients had decrease in grade of fibrosis and 17.24% showed no change while 10.34% of patients showed progression of fibrosis grade. Patients with MMR score ≥ 2 (n=4) and those with progression of fibrosis grade (n=3) showed suboptimal molecular response (BCR-ABL transcripts > 10%). Pretherapy mean MVD of patients (14.69 ± 5.28) was higher than that of controls (6.32 ± 1.64). A significant reduction of 66.51% was observed in posttherapy mean MVD (4.98 ± 2.77) of CML patients (p<0.001). CONCLUSION: Imatinib therapy in CML not only decreases marrow cellularity, but also helps towards normalization of bone marrow microenvironment by reducing fibrosis and angiogenesis.