Enteric Fever-Associated Hemophagocytic Lymphohistiocytosis: A Systematic Review of Clinical Characteristics and Outcomes.

Enteric fever is a major contributor to rising health care costs in developing countries. Associated disease-related complications and drug resistance further compound this problem. Hemophagocytic lymphohistiocytosis (HLH) is an uncommon complication of enteric fever with high morbidity and mortality. This systematic review aimed to evaluate the clinical characteristics and treatment outcomes in enteric fever-associated HLH syndrome. We searched major electronic databases (PubMed, Google Scholar, and Scopus) to identify the cases of enteric fever associated with HLH from inception until June 2023. Prespecified data regarding clinical presentation, outcomes, and HLH therapy were collected. A total of 53 cases of enteric fever with HLH were included in the final analysis. The mean age of patients was 20 years, and the proportions of female and pediatric patients were 52.8% and 45.3%, respectively. The mean duration of illness was 10.4 days. A total of 39.6% of patients had enteric fever-associated complications; coagulopathy and encephalopathy were the most common (23.1% and 13.5%). The overall mortality rate was 9.4% in HLH. A total of 51% of patients received HLH-specific therapy (corticosteroids in 41.5% and intravenous immunoglobulin in 20.8% of patients). On multivariate analysis, high ferritin levels (≥5,000 ng/mL) were significantly associated with mortality (hazard ratio, 3.01; 95% CI = 0.62-14.12, P = 0.041). Enteric fever with secondary HLH is associated with high mortality. This review reveals the potential role of ferritin in disease prognosis. In cases with significantly elevated ferritin levels, the role of immunosuppressants or combination antibiotics should be explored.

Case of angioimmunoblastic T-cell lymphoma presenting as peripheral and bone marrow plasmacytosis: A diagnostic conundrum.

ABSTRACT: Angioimmunoblastic T-cell lymphoma (AITL), a subtype of peripheral T-cell lymphoma (PTCL), is associated with unique clinical, morphological, and immunohistochemical features. The peripheral circulation might show presence of an occasional reactive plasma cell but significant plasmacytosis masquerading as plasma cell leukemia is rare. We report a case of AITL in a 42-year-old male, who presented with two-month history of generalized lymphadenopathy. On investigations, he had hypergammaglobulinemia and plasmacytosis in the peripheral blood and bone marrow masquerading as plasma cell leukemia. Immunohistochemistry and serum protein electrophoresis revealed polyclonal nature of plasma cells. Diagnosis of AITL was made on cervical lymph node biopsy. This case highlights the diagnostic challenge faced due to heterogeneity in the clinical presentation and pathological findings and to alert the clinician so that timely accurate diagnosis can be made to initiate the treatment.

Risk factors and associated pathway for rural and urban unmet dental prosthetic needs among older adults in Central India.

AIM: This study was undertaken to evaluate the risk factors and associated pathways for unmet dental prosthetic needs among older adult population in Central India. METHODS: A total of 11,145 randomly selected older adults participated in the study; 4613 from urban region and 6532 form rural region. Oral examinations were conducted at individual households for recording dental caries, periodontal disease, prosthetic status and needs. Structural Equation Modelling (SEM) was used to examine relationship between a set of exogenous variables and unmet dental prosthetic needs with variables that remained significant in the adjusted multilevel logistic model. Path coefficients were calculated for all variables with 95% confidence interval. Goodness of fit of the model was assessed by several indices. RESULTS: A total of 8433 (75.7%) participants had never visited a dentist and 9139 (82%) had unmet dental prosthetic needs. Dental caries was observed among 3207 (69.5%) and 4644 (71.1%) study participants from urban and rural regions respectively (p < .05). Low utilization of dental services was associated with high dental prosthetic needs in upper arch and lower arch (PC = -0.05, 0.001) and DMFT was associated with lower utilization of dental services (PC = -0.09, 0.001). DMFT was also associated with age, annual income, level of education, paternal education, type of family, tobacco consumption and CPI score in the hypothesized model. The fit indices used indicated that the model was adequate. CONCLUSIONS: Dental prosthetic needs in the proposed pathway model was associated with low utilization of dental services, dental caries, periodontal disease and other socio-demographic factors.

Evaluation of Diagnostic Usefulness of CD200 Expression in B-cell Chronic Lymphoproliferative Disorders.

Immunophenotyping by flow cytometry (FCM) is a useful diagnostic tool for the evaluation of mature B-cell neoplasms (MBN). Here, CD200 expression may play a significant role and improve the distinction between various MBNs, but any potential as a prognostic marker is yet to be established. The present prospective study was conducted on all the suspected cases of MBNs. Immunophenotyping was done using a BD FACS Canto FCM using a panel of 4 to 6 color combinations of monoclonal antibodies; CD45, CD34, CD5, CD19, CD20, CD22, CD23, CD79b, FMC7, CD10, CD38, ZAP70, CD200, IgG, IgM, CD25, CD103, CD2, CD3, CD11c as well as κ and λ light chains. CD200 expression was compared in different subgroups. Of the total of 130 cases included in the study, CD200 was positive in 118 cases (90%). CD200 was expressed in 100% of the cases of CLL(86 cases), atypical CLL(06 cases), HCL(14 cases), FL(02 cases), SMZL(04 cases), LPL (01 case), and low-grade NHL (05 cases), with the highest intensity of fluorescence in HCL followed by CLL. All the cases of MCL and PLL were exclusively negative for CD200. In conclusion, the results of the present study support inclusion of this marker in the flow cytometric panels for the differential diagnosis of MBNs.

Iron Deficiency Anemia Presenting With Pancytopenia: A Study From India.

INTRODUCTION: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. IDA is commonly associated with thrombocytosis and normal or slightly decreased leukocyte count. Sometimes it can present with thrombocytopenia, but rarely present with pancytopenia. Here we are presenting six cases of severe iron deficiency presenting with pancytopenia, which responded to iron replenishment. METHODS:  This 12-month observational study was conducted in the Department of General Medicine at a tertiary care Centre in India. All cases of pancytopenia (after exclusion of other causes) with IDA were included. IDA was established with the help of a complete blood count (CBC), peripheral smear examination, serum iron studies, and serum ferritin.  Results: In our study, CBC at four weeks later of iron transfusion without other supplementation showed significant improvement in hematological parameters. CONCLUSION:  Severe iron deficiency is a reversible etiology of pancytopenia. It should be kept as a differential diagnosis of pancytopenia if common causes of pancytopenia are ruled out.

Association of iron-related biomarkers with severity and mortality in COVID-19 patients.

BACKGROUND: Nutritional deficiency is associated with weaken immune system and increased susceptibility to infection. Among other nutrients, several trace elements have been shown to regulate immune responses. Iron is one of the most abundant trace elements present in our body, which is required in various biological processes. Iron has an immunomodulatory function and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of different iron-related biomarkers in association to severity and mortality in SARS-CoV-2 patients. MATERIALS AND METHODS: A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate, and severe) and outcome (discharged or deceased). Serum iron, TIBC, ferritin, transferrin, transferrin saturation levels were analyzed by the direct colourimetric method. RESULTS: In cases the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 29 µg/dL, 132.53 µg/dL, 106.3 mg/dL, 17.74 % and 702.9 ng/dL respectively. Similarly, in controls the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 53 µg/dL, 391.88 µg/dL, 313.51 mg/dL, 12.81 % and 13.52 ng/dL respectively. On comparing the cases with the controls, a significant lower level of iron, TIBC, and transferrin were found in the cases along with the significant higher levels of ferritin and transferrin saturation. On comparing the Receiver operating characteristic (ROC) curves of Iron, Ferritin, Transferrin, Transferrin sat % and TIBC in relation to survival in COVID-19 patients it was found that iron, followed by transferrin and ferritin has the highest area under the curve (AUC) with 74 %, 63 % and 61 % respectively. Further, in pairwise analysis of ROC curve, a significant difference was found between the Iron-transferrin (p < 0.01), iron-TIBC (p < 0.001) and transferrin-ferritin (P < 0.01). The multiple regression model based on Iron and transferrin outperformed any other combination of variables via stepwise AIC selection with an AUC of 98.2 %. The cutoff point according to Youden's J index is characterized with a sensitivity of 98 % and a specificity of 96.8 %, indicating that iron along with transferrin can be a useful marker that may contribute to a better assessment of survival chances in COVID-19. CONCLUSION: Our study demonstrated a significantly decreased levels of iron, TIBC, & transferrin and a significantly increased levels of ferritin and transferrin saturation in COVID-19 patients when compared with controls. Further, Iron and transferrin were observed to be a good predictor of mortality in patients with COVID-19. From the above analysis we confirm that iron-related biomarkers play an important role in the development of oxidative stress and further lead to activation of the cytokine storm. So, continuous monitoring of these parameters could be helpful in the early detection of individuals developing the severe disease and can be used to decrease mortality in upcoming new waves of COVID-19.

Splenic Infarct as the Presenting Manifestation of Essential Thrombocythemia.

Background: Essential thrombocythemia is a chronic myeloproliferative neoplasm characterized by thrombotic and hemorrhagic complications. Essential thrombocythemia can be considered a risk factor for thrombotic events. Case Report: A 34-year-old female presented with sudden onset of abdominal pain from splenic infarction for which she underwent splenectomy. Bone marrow examination performed because of increasing thrombocytosis led to a diagnosis of essential thrombocythemia. Postoperatively, she was maintained on low-dose aspirin and doing well at follow-up. Conclusion: Our patient had an undiagnosed case of essential thrombocythemia and presented with symptoms related to splenic infarction. To the best of our knowledge, few cases of splenic infarction consequent to essential thrombocythemia have been reported.

Predictors of Clinical Outcomes in Adult COVID-19 Patients Admitted to a Tertiary Care Hospital in India: an analytical cross-sectional study.

BACKGROUND: The outbreak ofsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted inexponential rise in the number of patients getting hospitalised with corona virus disease 2019 (COVID-19). There is a paucity of data from South East Asian Region related to the predictors of clinical outcomes in these patients. This formed the basis of conducting our study. METHODS: This was an analytical cross-sectional study. Demographic, clinical, radiological and laboratory data of 125 patients was collected on admission. The study outcome was death or discharge after recovery. For univariate analysis, unpaired t-test, Chi-square and Fisher's Exact test were used. Receiver operating characteristic (ROC) curves were plotted for Sequential Organ Failure Assessment (SOFA) score and few laboratory parameters. Logistic regression was applied for multivariate analysis. RESULTS: Elderly age, ischemic heart disease and smoking were significantly associated with mortality. Elevated levels of D-dimer and lactate dehydrogenase (LDH) and reduced lymphocyte counts were the predictors of mortality. The ROCs for SOFA score curve showed a cut-off value ≥ 3.5 (sensitivity- 91.7% and specificity- 87.5%), for IL-6 the cut-off value was ≥ 37.9 (sensitivity- 96% and specificity- 78%) and for lymphocyte counts, a cut off was calculated to be less than and equal to 1.46 x 109per litre (sensitivity-75.2%and specificity- 83.3%). CONCLUSION: Old age, smoking history, ischemic heart disease and laboratory parameters including elevated D-dimer, raised LDH and low lymphocyte counts at baseline are associated with COVID-19 mortality. A higher SOFA score at admission is a poor prognosticator in COVID-19 patients.

Is Priapism a Common Presentation of Chronic Myeloid Leukemia in an Adolescent Patient?

Chronic myeloid leukemia (CML) is predominantly a disease of adults and the elderly. CML is uncommon in the paediatric age. Priapism as an initial presentation is quite uncommon in CML and is rare in the case of CML in paediatric and adolescent age. We present a case of CML in an adolescent male who presented with priapism of 48 hours duration. The patient was managed in an emergency by corporal aspiration and saline irrigation and was found to have CML during a hospital stay. The patient was treated with imatinib and is under follow-up for the last two years.

Haemophagocytic lymphohistiocytosis secondary to brucellosis in a young child.

Brucellosis is a common zoonotic disease worldwide. It has protean clinical manifestation and sometimes may has a life-threatening complication. A 4-year-old boy presented with a history of fever, myalgia and appetite loss for 3 weeks. On examination, he had hepatosplenomegaly. The initial working diagnosis was an infection, autoimmune disease and malignancy. Investigations showed positive Brucella serology, and he was started on rifampicin and cotrimoxazole. He was further investigated because of persistent fever, which revealed evidence of haemophagocytic lymphohistiocytosis (HLH). He continued treatment for brucellosis, except rifampicin which was replaced with doxycyclin due to a worsening liver function. The child showed complete clinical and biochemical improvement after 6 weeks of therapy. HLH is a life-threatening condition and should be suspected in children with brucellosis, who did not respond to appropriate antibiotics treatment. Secondary HLH does not always require specific therapy; it may improve with adequate treatment of the underlying condition.

Pseudothrombocytosis in Case of Betathalassaemia Intermedia Masquerading as Myeloproliferative Neoplasm.

Finding spurious thrombocytopenia is a common occurrence in clinical practice, whereas pseudothrombocytosis is a very uncommon event. Despite several technical advancements in automated haematology analysers, a careful peripheral smear examination remains standard examination in cases of discrepancy of platelet counts. We are presenting a case of betathalassaemia intermedia who had pseudothrombocytosis, which was falsely labelled as myeloproliferative neoplasm before the patient visited our haematology clinic.

Disseminated tuberculosis in children-a difficult diagnose depends on how far we can go.

Tuberculosis (TB) is an important public health problem in developing countries. In India, despite substantial efforts targeting TB and its associated risk factors, the number of cases remains high with 2.7 million new cases per year with a minimum 10% case contributed by paediatric TB. Disseminated TB has been increasingly recognised in children in recent times due to the increased prevalence of immune suppression secondary to AIDS and immunosuppressive therapies for various medical disorders and increasing awareness. Here we describe a 5-year-old girl who presented with fever of unknown cause, and her diagnosis of disseminated TB was delayed due to atypical presentation and the paucibacillary nature of paediatric TB. It was a bone marrow examination report which led us to clinch the diagnosis. The case highlights the difficulty in diagnosing disseminated TB and the importance of bone marrow examination in such cases.

Genetic Implications of HLA-DR and HLA-DQ Genotype on Tobacco Smoking and Oral Submucous Fibrosis.

PURPOSE: Integration of genetic information into our understanding of oral diseases has fostered the hope to intervene the disease process among genetically susceptible individuals. Oral submucous fibrosis (OSF) (mainly in the Southeast Asia region) and tobacco smoking are two of the major public health problems the world is facing today. With more and more diseases being associated with alleles of the human leukocyte antigen (HLA), the objective of the study was to explore any genetic association of OSF and smoking behaviour with specific HLA Class II DQB1*0503 and HLA DRB1*0301 alleles. MATERIALS AND METHODS: Genomic DNA was extracted from saliva of 64 patients divided into an OSF group, a tobacco smokers group and a control group. This was followed by polymerase chain reaction (PCR) with sequence-specific primer of HLA-DQB1*0503 and HLA DRB1*0301 allele, visualised under 2% agarose gel. RESULTS: A statistically significant difference was observed between the OSF group and controls in presence of HLA-DQB1*0503 allele, with 84% of the patients showing the presence. Frequency of HLA DRB1*0301 allele was also found to be significantly higher (72%) among OSF patients (p <0.001). Similar results were shown in tobacco smokers with 28% cases showing presence of HLA DRB1*0301 allele and 13 (52%) of them having DQB1*0503 allele (p <0.001). CONCLUSION: HLA-DRB1*0301 and HLA-DQB1*0503 are statistically significantly associated with susceptibility to OSF and smoking behaviour.

Hypercalcemic Encephalopathy as an Initial Presentation of Multiple Myeloma.

We report the case of an 84-year-old female presented to us with acute onset altered sensorium. On investigation, neurological and infectious causes were ruled out. On further evaluation, her serum calcium was found elevated (15.07 gm/dl). The diagnosis of hypercalcemic encephalopathy was made with the possibility of multiple myeloma due to raised total protein and globulin levels. Serum electrophoresis, immunofixation, and bone marrow examination confirmed the diagnosis of multiple myeloma. The patient was treated with bortezomib, dexamethasone, and lenalidomide. After 1 week, she improved with normalization of serum calcium. Herein, we highlight hypercalcemia as an important cause of encephalopathy. As our report suggests, metabolic encephalopathy can be the first presentation in multiple myeloma.

Creutzfeldt-Jakob disease with unusual presentation of peripheral neuropathy and ophthalmoplegia.

Creutzfeldt-Jakob disease (CJD) is a well-described disease. It is characterized by rapidly progressive dementia, myoclonus, ataxia, pyramidal, and extrapyramidal signs. There are well-defined electroencephalogram and magnetic resonance imaging (MRI) findings, and markers found in the cerebrospinal fluid (CSF). The gold standard for diagnosing CJD remains brain biopsy. We present a case of a patient with a family history of biopsy-proven CJD who initially presented with symptoms of peripheral neuropathy. A month later, he developed ataxia, ophthalmoparesis, and then dysarthria. His initial workup was relatively unrevealing, showing an elevated protein in his CSF. He was thought to have Miller Fisher syndrome variant of Guillain-Barré syndrome. He neither, however, responded to plasmapheresis nor IVIG. He later started to develop progressive dementia. Repeated MRI showed restricted diffusion in the caudate and putamen, as well as in the cortex (cortical ribboning). Lumbar puncture was then found to be positive for 14-3-3 protein, total-tau protein, and real-time quaking-induced conversion assay, which are highly suggestive of CJD. We present a case of CJD with an unusual presentation resulting in misdiagnosis, prolonged workup, and potentially harmful treatment modalities. This case highlights the importance of broadening our definition of CJD to encompass more cases with unusual presentations.

Focal segmental glomerulosclerosis in a patient with prefibrotic primary myelofibrosis.

We report a case of 56-year-old man presented to us with chief complaints of frothy urine and leg swelling. A urinalysis revealed nephrotic-range proteinuria. Haematological investigations revealed thrombocytosis, leucocytosis and peripheral blood smear showed a leucoerythroblastic picture. JAK 2 mutation was positive. To confirm the diagnosis of myeloproliferative neoplasm, bone marrow biopsy was done, which was suggestive of primary myelofibrosis. The patient underwent kidney biopsy due to rapidly declining renal function and persistent proteinuria, which was suggestive of focal segmental glomerulosclerosis. Early glomerulopathy is rare in myeloproliferative neoplasm, and aggressive follow-up is required to prevent progression of kidney disease.

Evaluation of platelet surface glycoproteins in patients with Glanzmann thrombasthenia: Association with bleeding symptoms.

BACKGROUND & OBJECTIVES: Glanzmann thrombasthenia (GT) is a rare, inherited autosomal recessive disorder characterized by qualitative or quantitative deficiency of integrin αIIbß3 [glycoprotein IIb (GPIIb)/IIIa, CD41/CD61] diagnosed by absent or reduced platelet aggregation to physiological agonists, namely, collagen, adenosine-di-phosphate, epinephrine and arachidonic acid. The objective of this study was to quantitate platelet surface GPs, classify GT patients and relate the results with the severity of bleeding and platelet aggregation studies. METHODS: Fifty one patients of GT diagnosed by platelet aggregation studies were evaluated for the expression of CD41, CD61, CD42a and CD42b on platelet surface by flow cytometry. The association between the clinical phenotype based on bleeding score and GT subtype on flow cytometric evaluation was assessed. RESULTS: Twenty four (47%) patients of GT were classified as type I (as CD41/CD61 were virtually absent, <5%), six (11.8%) patients as type II (5-20% CD41/CD61) and 21 (41.2%) as type III or GT variants as they had near normal levels of CD41 and CD61. Type III GT patients had significantly lower numbers of severe bleeders (P=0.034), but the severity of bleeding did not vary significantly in type I and II GT patients. In all GT patients, mean CD41 expression was found to be lower than mean CD61 expression (P=0.002). INTERPRETATION & CONCLUSIONS: Type I GT was found most common in our patients and with lowered mean CD41 expression in comparison with CD61. Type III GT patients had significantly lower numbers of severe bleeders, but the severity of bleeding did not vary significantly in type I and II GT patients.