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.].

Peripancreatic tuberculosis.

Peripancreatic tuberculosis (PTB) is a very rare variant of tuberculosis and its clinical and radiological findings are similar to those of pancreatic malignancy. Diagnosis of PTB is usually incidental and is made after surgical resection. We are presenting a male patient who had complaints of prolonged fever, significant weight loss and yellowish discolouration of eyes and dark-coloured urine. Investigations revealed that there was a pancreatic mass causing obstructive jaundice. However, the aetiology of the mass, whether tubercular or malignant, was not clear. Hence, the patient was planned for endoscopic ultrasound-guided fine needle aspiration cytology. Cytology and aspirate were sent for a cartridge-based nucleic acid amplification test which revealed the presence of Mycobacterium tuberculosis, sensitive to rifampicin. The patient improved completely after treatment with antitubercular therapy.

Evaluation of visual evoked potential in chronic myeloid leukemias.

BACKGROUND: Visual complaint is not very uncommon in chronic myeloid leukemia (CML) patients. Our study aims to evaluate the visual pathway using visual evoked potential (VEP) in cases of CML at the time of diagnosis and 6 weeks after tyrosine kinase therapy, to find out treatment impact in asymptomatic as well as symptomatic individuals and compare it with the general population. MATERIALS AND METHODS: This is an analytical cross-sectional study. The study group comprised 20 newly diagnosed cases of CML and 20 age- and sex-matched healthy control population. A thorough history and clinical examination with detailed ophthalmological studies, including VEP, were done. Cases who had VEP abnormalities were then followed-up after 6 weeks post-Imatinib therapy and underwent repeat investigations, including VEP. RESULTS: VEP in cases was significantly deranged (P < 0.001), where 15 patients (75%) had abnormalities in VEP compared to 3 (15%) in control. Post 6 weeks chemotherapy, Out of 10 cases that were followed up, 7 patients had achieved hematological remission with normal VEP finding (P = 0.02). Simultaneously, an increase in hemoglobin (P = 0.002) and reduction in total leukocyte count (TLC) (P = 0.004) were observed. CONCLUSION: Considerable evidence appear to support the notion that CML patients have a higher prevalence of ophthalmic manifestations as compared to the general population, which can be screened earlier with objective tests like VEP. Concurrently, hematological parameters and VEP showed derangement at the time of diagnosis. After 6 weeks of Imatinib treatment, the improvement in VEP can then be attributed to a reduction in TLC. Hence it can be deduced that VEP has paramount importance in the early identification of ophthalmic manifestations, which are reversible with timely treatment.

Primary hepatoid adenocarcinoma of lung: A rare malignancy mimicking tuberculosis.

Hepatoid adenocarcinoma of lung (HAL) is a rare aggressive malignant tumour which histologically resembles hepatocellular carcinoma (HCC). Hepatoid adenocarcinoma (HAC) mostly produces high levels of alphafetoprotein (AFP) and is frequently found in extrahepatic organs including stomach, testes, ovaries, lungs and pancreas. Our patient was a male in his 40s with a chronic smoking history, presented with complaints of fever, weight loss, cough and anorexia for one month. On the basis of history, examination and initial investigation patient were started on empirical antitubercular therapy. However, within a span of 10 days, patient's condition worsened, and he developed a pulmonary embolism, which despite adequate treatment did not improve and the patient succumbed to his illness. Postmortem biopsy revealed a rare primary lung tumour, HAL.

Disseminated tuberculosis presenting as cutaneous leucocytoclastic vasculitis.

Cutaneous leucocytoclastic vasculitis (CLV) is a type of small vessel vasculitis, predominantly presenting with palpable purpuras and sometimes with systemic manifestations. The following report describes the case of a woman, who presented with fever, anorexia and maculopapular lesions over both lower limbs. Skin biopsy revealed CLV. CT scan demonstrated bilateral pulmonary nodules, ileocecal wall thickening and generalised lymphadenopathy. Colonoscopy guided biopsy obtained from ileocecal valve ulcer showed epitheloid cell granuloma with Langhans-type giant cells and caseous necrosis. Rapid clinical improvement was seen with anti-tubercular therapy. Among infectious causes, although rare and an uncommon presentation, Mycobacterium tuberculosis should be considered as an important cause of CLV.

Antiepileptic drug-induced severe granulomatous interstitial nephritis.

Granulomatous interstitial nephritis (GIN) is a type of tubulointerstitial nephritis characterised by tubulointerstitial infiltration of mononuclear cells and eosinophils. It accounts for about 6% of all tubulointerstitial nephritis and is detected in ∼0.5%-0.9% of all renal biopsies. GIN has been linked to several antibiotics, non steroidal anti-inflammatory drugs (NSAIDs), and granulomatous disorders like tuberculosis and sarcoidosis but is rarely reported with anti-epileptic medications like phenytoin and levetiracetam. We present a case report of a man in his early 20's with previously normal renal function who developed GIN following levetiracetam and phenytoin consumption for 7 years. After withdrawal of the causative drug and starting steroid therapy, his kidney function gradually improved. In cases of GIN, medication history is important in the evaluation of aetiology.

Comparison of Serum Holotranscobalamin with Serum Vitamin B12 in Population Prone to Megaloblastic Anemia and their Correlation with Nerve Conduction Study.

Early detection of megaloblastic anemia and associated neurological complications is crucial for management. This study was conducted to compare serum holotranscobalamin level with serum vitamin B12 level as early biomarker in people prone to megaloblastic anemia and to evaluate co-relation between these biomarkers and nerve conduction study in study patients. 83 adult patients (Hb > 12 gm/dl) prone to megaloblastic anemia were studied for basic haematological investigations, random blood sugar, thyroid function test, liver function test, kidney function test, serum vitamin B12, serum holotranscobalamin and serum folic acid levels. 45 patients among them underwent nerve conduction studies. All study patients were classified in 6 groups on the basis of risk factors for megaloblastic anemia. 29 patients (34.9%) were on antiepileptic drugs, 26 (31.3%) were chronic alcoholic, 10 patients (12%) each, had malabsorption and ileal tuberculosis, 6 (7.22%) had chronic pancreatitis and 2 (2.4%) had ileal resection. 30 patients (36.14%) had low serum holotranscobalamin, including 7 patients (8.43%) with low serum vitamin B12 level also, unmasking vitamin B12 deficiency in 23 patients (27.7%). 7 patients (8.43%) had mean corpuscular volume (MCV) > 100fL and 8 patients (9.63%) had vitamin B12 deficiency related changes on peripheral smear. Serum vitamin B12 and holotranscobalamin levels were significantly low in patients with peripheral smear changes, with p value 0.039 and 0.041 respectively, while no such association seen with MCV. Subclinical peripheral neuropathy was detected in 18 (40%) out of 45 patients on nerve conduction study. Serum holotranscobalamin levels were significantly lower (p = 0.031) than serum vitamin B12 levels (p = 0.2) in patients with neuropathic changes. Rest investigations and serum folic acid levels were normal in all patients. Holotranscobalamin levels can be considered early and reliable marker for vitamin B12 deficiency and deficiency associated peripheral neuropathy, even in patients who are prone to megaloblastic anemia, and not yet anemic or symptomatic for neuropathy.

Tuberculoma - a great mimicker: can diffusion tensor imaging and tractography help?

BACKGROUND: Central nervous system (CNS) tuberculomas often mimic tumors on conventional imaging, differentiation of which may not be possible without invasive tissue sampling. Diffusion tensor imaging (DTI), owing to its unrivalled property of characterizing molecular diffusion, may help in better lesion characterization and tractography may help understand the pattern of white matter involvement by tuberculomas. PURPOSE: To estimate qualitative and quantitative diffusion tensor changes in brain tuberculomas and to evaluate patterns of white matter involvement using 3D tractography. MATERIAL AND METHODS: Thirty patients with brain tuberculomas were evaluated on a 3-T magnetic resonance scanner. Diffusion tensor images were acquired along 20 non-colinear encoding directions with two b-values (b = 0, b = 1000). Regions of interest (ROIs) were drawn on quantitative fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps in the center of the tuberculoma and perilesional area. Similar ROIs were placed in contralateral hemispheres for comparison. Tractography maps were also generated. RESULTS: Mean FA in the center and perilesional area of tuberculomas were 0.098 ± 0.041 and 0.311 ± 0.135, respectively. ADC values in corresponding regions were 0.920 ± 0.272 ×10-3 mm2/s and 1.157 ± 0.277 ×10-3 mm2/s. These values were significantly different compared to contralateral similar brain parenchyma. Tractography revealed interruption of white fibers in the center with deviation of fibers at the periphery in the majority of tuberculomas with none showing infiltration of white matter described in tumors. CONCLUSION: Significant qualitative as well as quantitative DTI changes were seen in tuberculoma and perilesional areas compared to contralateral hemisphere with tractography showing a pattern different from that described in tumors. These findings may help to differentiate tuberculomas from infiltrating tumors.

Assessing Menstrual Changes Among Young Indian Females Post-SARS-CoV-2 Vaccination.

Background The rollout of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has significantly enhanced immunity against coronavirus disease 2019 (COVID-19), leading to a reduction in the severity of illness, hospitalizations, and deaths. While various side effects of the vaccine have been reported, its impact on the menstrual cycle remains unclear. Methods We conducted a cross-sectional study involving university students who had received either partial or full vaccination against SARS-CoV-2. Data was gathered through a questionnaire designed to assess the relationship between menstrual changes and the SARS-CoV-2 vaccination. Results A total of 773 participants, with a mean age of 20.6 ± 1.7 years, were included in this study. The participants reported a significant increase in the irregularity of the menstrual cycle. We observed a slight increase in the length of the menstrual cycle, from 30.0 ± 4.0 days (pre-vaccination) to 30.5 ± 5.6 days (post-vaccination), which was statistically significant (p<0.001). The duration of menstruation also increased, from 4.9 ± 1.7 days (pre-vaccination) to 5.0 ± 1.7 days (post-vaccination). However, this increase in menstrual length due to vaccination was not statistically significant (p = 0.898). Notably, there was a significant increase in pain reported by the participants after receiving the SARS-CoV-2 vaccine (p = 0.004). Conclusion The SARS-CoV-2 vaccination significantly impacted the regularity of the menstrual cycle, length of the menstrual cycle, and pain during menstruation, though temporarily. Our study found no significant differences in menstrual changes or the type of vaccine administered (Covishield and Covaxin).

Transformation of diffuse large B-cell lymphoma to lymphoblastic lymphoma.

Transformations in diffuse large B-cell lymphoma (DLBCL) are extremely rare. Here, we are presenting a very rare case of DLBCL transforming into lymphoblastic lymphoma (LBL) diagnosed by fine-needle aspiration cytology (FNAC) and flow cytometry. A 31-year old male on antiretroviral therapy and a known case of diffuse large B-cell lymphoma diagnosed 1 year back on cervical lymphadenopathy, presented with left axillary swelling for 3 months. FNAC and Flow cytometry were performed from the left axillary swelling which confirmed the diagnosis of LBL.

Diagnostic utility of flow cytometry in identifying histiocytic sarcoma-A case report.

Histiocytic sarcoma (HS) is a malignant neoplasm of hematopoietic origin. It is an exceedingly rare and aggressive malignancy commonly seen in adults. Diagnosis is difficult owing to lack of specific clinical manifestations with the absence of precursor lesions or causative agents. Hence, it primarily relies on histopathological morphology combined with immunohistochemistry, which is time-consuming, hence resulting in delayed treatment. However, diagnostic utility of flow cytometry is not well established in this. We report a case of a 45-year-old man who presented with right axillary lymphadenopathy for 1 month. FNAC was performed on the axillary lymph node, which showed large, atypical lymphoid/histiocyte-like cells. On flow cytometry, these cells were CD64+, CD11c+, and CD45+ suggesting histiocytic sarcoma. Similar morphology was seen on incisional biopsy. On immunohistochemistry, the cells were negative for B and T cell markers, PAX5, EMA, CK, ALK, and CD1a and expressed CD68, S100, and CD11c. A diagnosis of histiocytic sarcoma was made. Hence, flow cytometry can be a highly effective and powerful tool for the early detection of HS and can help in prompt treatment, given its aggressive clinical course and low survival interval.

Evaluation of Use of RPMI Medium to Preserve Cell Morphology for Pleural/Peritoneal Fluid Cytology.

Introduction: Cytologic evaluation is the best way to detect the presence of malignancy in body cavity fluids. Roswell Park Memorial Institute (RPMI) medium or RPMI 1640 is used in cell culture, tissue culture, and also to improve the cellularity and morphology of CSF cytology specimens. Objectives: To determine whether RPMI medium can be used to preserve cell morphology in pleural/peritoneal effusion samples. Method and Material: The study was conducted on 30 pleural/peritoneal fluid samples received routinely during 2 months for diagnostic purposes in our department. The samples were divided into four parts. One-fourth of the sample was directly refrigerated and the other fourth was at room temperature. In the other two parts, an equal volume of RPMI media was added, and one was kept at room temperature and the other refrigerated. These cytospin-prepared Giemsa-stained smears were examined for cell morphology, cellularity, and occurrence of bacterial colonies at 24 h, 48 h, 72 h, and 1 week, respectively. Result: Refrigerated RPMI medium is the best preservative for pleural/peritoneal samples; however, samples with RPMI at room temperature were equivalent/even worse than the simple refrigerated sample.

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.

Elevated levels of vascular endothelial growth factor in adults with severe dengue infection.

The immune pathogenesis of dengue involves antibody production, B cell and T cell response and various pro-inflammatory and anti-inflammatory cytokines. VEGF, a potent permeability enhancing cytokine, is thought to play a pivotal role in mediating plasma leakage in DHF. It is a member of growing family of related proteins that includes VEGF B, VEGF C, VEGF D and placental growth factor. It promotes angiogenesis and vascular integrity. In addition to its role in promoting endothelial permeability & proliferation, it may contribute to inflammation and coagulation. This study was undertaken to investigate the role of VEGF in the patients with dengue infection. Sera were collected from 106 patients with various grades of dengue illness and 40 healthy controls and tested for VEGF levels using commercial ELISA kits. Viral serotypes were detected using specific primers. The results showed very low levels of VEGF (3.493 ± 1.982 pg/ml) in healthy controls. Levels of VEGF were higher in patients with severe dengue (428.170 ± 224.61 pg/ml) as compared to patients with non severe dengue with and without warning signs (290.407 ± 167.17 pg/ml). Significant correlation (p < 0.001) was found between raised VEGF levels and thrombocytopenia and raised haematocrit levels. The VEGF profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression of dengue fever to severe dengue infection.

Treatment for tuberculosis in a patient with Dubin-Johnson syndrome.

Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder characterised by conjugated hyperbilirubinemia resulting from mutations of ABCC2/MRP2 gene. The beneficial effects of ursodeoxycholic acid (UDCA) and rifampicin were found to be complementary in the treatment of cholestatic liver disease secondary to DJS. We present a case of a young woman with tubercular meningitis. She was started on modified antitubercular therapy in view of conjugated hyperbilirubinemia. However, reinitiation of rifampicin resulted in redevelopment of jaundice. Liver biopsy was suggestive of DJS. The patient was started on rifampicin along with UDCA. There was improvement in hyperbilirubinemia and a full course of antituberculous therapy without further worsening of the disorder was possible. This is a rare case of DJS with tuberculosis, showing beneficial effects of rifampicin and UDCA combination therapy, which so far has been considered doubtful. It is uncertain what the level of efficacy of therapy is in various MRP2 gene mutations.