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Fever of unknown origin is always a diagnostic challenge in establishing etiology. A gentleman in his 70s presented with complaints of fever and dry cough for 2 months duration. We proceeded with contrast imaging of the thorax and abdomen which revealed mild hepatomegaly. Bone marrow examination with bone marrow culture and 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT). Bone marrow aspirate smears were hypercellular with around 50% atypical lymphoid cells with plasmacytoid and bizarre morphology with few multilobed nuclei. Bone marrow biopsy revealed predominantly sinusoidal involvement by neoplastic cells. On immunohistochemistry, tumor cells were positive for CD45, CD79a, CD20, and MUM1 and were negative for CD5, CD10, and BCL6. Ki-67 was around 60% in tumor cells. FDG PET/ CT revealed diffusely increased uptake in the both axial and appendicular skeleton with (SUVmax 5.06) and diffusely increased FDG uptake (SUVmax 3.67) noted in the spleen. As intravascular large B-cell lymphoma is a highly aggressive non-Hodgkin lymphoma with a high risk of central nervous system involvement, we treated it with chemoimmunotherapy (R-CHOP) with intrathecal methotrexate. After a clinical follow of 3 months, the patient developed relapsed with a soft-tissue swelling over the right leg. The patient was treated with two cycles of R-DHAP and had progressive disease and started on Ibrutinib, Lenalidomide, and Rituximab (2 cycles). Post two cycles, the patient had progressive disease and switched to acalabrutinib based therapy. After 1 month of acalabrutinib-lenalidomide-rituximab therapy, the patient had disease progression and succumbed to the disease.

Lenalidomide (LND) is an analogue of thalidomide that is second generation immunomodulatory drugs (IMiDs). LND contains asymmetric carbon atom and exist R and S enantiomer. S (-) form of enantiomer are considered to be more potent and biologically active in tumor cell. It is available in racemic form for clinical use. The study aims to develop and validate enantiomer separation of LND in human plasma. The chromatographic enantiomeric separation was achieved on a Daicel-CSP, Chiralpack IA 4.6 × 250 mm_5 μm. The mobile phase was constituted in combination of methanol:glacial acetic acid at a concentration of 499.50 ml: 50 μl. UV wavelength detection was 220 nm. The RSD% for all validation parameters was found to be within the acceptable limit. The chiral chromatographic (chiral stationary phase-high-performance liquid chromatography [CSP-HPLC]) method developed and validated for the quantitative estimation of LND enantiomers S (-) and R (+) in human plasma sample is accurate, precise, robust, stable and selective.

Objectives: This study aimed to study the correlation between Breakpoint Cluster Region- ABelson Leukemia virus 1 transcript levels at 3 months with the treatment responses at 6 and 12 months in patients on imatinib. Around 30% of patients with chronic myeloid leukemia (CML) might have treatment failure with the first-line tyrosine kinase inhibitors (TKI). Patients with a “warning response” at 3 months can continue therapy with the same TKI while monitoring for disease progression. However, newer pieces of evidence suggest that patients who fail treatment with imatinib do have suboptimal responses in the early time points, and hence, 1st 3-month assessment might be a useful indicator for future treatment failure. Material and Methods: It is a single-center prospective observational study involving 60 treatment-naive consecutive patients with CML-chronic phase who attended Hematology Outpatient Department at IHTM, Kolkata. Treatment responses were assessed by cytogenetics and BCR-ABL1 transcript levels by real-time quantitative polymerase chain reaction at 3 monthly time points. Results: About 51% and 70.2% of the study participants achieved complete cytogenetic response at 6 and 12 months, respectively. About 74% of the participants had achieved early molecular response (EMR) at 3 months. The failure rates of cytogenetic responses were 13% and 20% at 6 and 12 months, respectively. Patients who failed to achieve EMR at 3 months had higher failure rates at 6 months. The major, warning and failure of molecular responses at 6 and 12 months were found to be 15%, 25%, and 9%, and 34%, 39%, and 27%, respectively. The analyses showed that patients who failed to achieve EMR at 3 months are also more likely to have the failure of molecular response at 12 months, with a statistical significance of P < 0.01. Failure of EMR at 3 months also correlated with failure of overall responses (both cytogenetic and molecular at 12 months) with a statistical significance of P = 0.006. When followed up, there was a progression of disease in three including a death in the suboptimal response group. Conclusion: Our patients had inferior treatment responses to imatinib than that observed in the previous studies. The majority have baseline fibrosis of the marrow and splenomegaly at presentation which might contribute to adverse outcomes. The molecular response at 3 months was found to be a consistent and powerful indicator of treatment responses at later time points.

The proteasome subunit β5 (PSMβ5) is a chief target of proteasome inhibitors (PIs) for treatment of multiple myeloma (MM). The relevance of PSMβ5 mutations and their functional impact on the development of resistance to PIs have been demonstrated recently. Therefore, this present study deals with an in-depth E-pharmacophore based screening and repurposing of FDA-approved drugs that could target PSMβ5 for MM. Our molecular docking-based investigation revealed risedronate and zoledronate as potential alternative therapeutic molecules for targeting the PSMβ5 gene. Risedronate and zoledronate displayed high binding affinity (−9.51 and −8.56kcal/mol respectively) to PSMβ5. Moreover, 100ns molecular dynamics simulation analysis of docking complexes revealed risedronate and zoledronate with a superior binding free energies and stable interactions with PSMβ5. The RMSD plot shows that the risedronate-PSMβ5 (mean: 0.24nm) and zoledronate-PSMβ5 (mean: 0.25nm) complexes are identical and stays stable until 100ns. We further validated the activity of zoledronate in MM cell lines RPMI8226 and U266 where zoledronate showed significant anti-proliferative and apoptotic activity. Importantly, zoledronate showed an enhanced anti-proliferative activity when combined with bortezomib in MM cell lines. Thus, this study demonstrates that combining bortezomib with zoledronate could have a significant impact on reducing MM cell growth and can be an alternative strategy for treating MM.

Scope and Significance: Pressure ulcers are very difficult to treat and pose an economic burden, just below cancer and cardiovascular illness, at 4.82 billion US dollars. It is important to understand the pathophysiology of the condition, risk stratification, and ways of preventing it. Prevention forms the most important aspect of their management. The authors systematically evaluated the existing risk prediction scales and explored the evidence from literature regarding the role of additional factors including body mass index, obesity, subcutaneous tissue thickness and skin integrity in pressure ulcers. With this review it is hoped that the future management of pressure ulcers will concentrate on the preventable as well as alterable factors in its pathophysiology.The review focuses on how adipose tissue thickness can predict the occurrence of pressure ulcer. If adequately proved that a definite thickness of peripheral adipose tissue is efficient in prevention of pressure ulcers, then methods of maintaining the thickness of this tissue will be the next effective strategy in the management of this chronic issue.The review addresses the management of pressure ulcers to wound care providers and emphasize on confounding parameters of obesity, subcutaneous tissue thickness, and skin integrity during the treatment regimen.The main objective of this review is to draw a consensus concerning the role of adipose tissue in pressure ulcers, based on the published research. A review of the various preexisting predictive scales for pressure ulcers is a secondary objective in order to highlight the shortcomings in the ulcer management. This review finally aims in the future at paving a way to refine our prognosticating scales for pressure sores based on these results. Accurate preventative injury risk scales are needed so that preventative resources can be directed to the patients for whom they are the most appropriate.

Next-generation sequencing (NGS) elucidates the diffuse large B-cell lymphoma (DLBCL) genetic characteristics by finding recurrent and novel somatic mutations. This observational study attempted to create an NGS panel with a focus on identifying novel somatic mutations which could have potential clinical and therapeutic implications. This panel was created to look for mutations in 133 genes chosen on basis of a literature review and it was used to sequence the tumor DNA of 20 DLBCL patients after a centralized histopathologic review.The study included 20 patients having DLBCL. The quality and quantity of tumor cells were accessed by HE staining and correlated with histopathology and Immunohistochemistry (IHC) status. Patients were grouped as ABC (activated B-cell), PMBL (primary mediastinal large B-cell lymphoma), and other or unclassified subtypes. The lymphoma panel of 133 was designed on targeted sequencing of multiple genes for the coding regions through NGS. The libraries were prepared and sequenced using the Illumina platform. The alignment of obtained sequences was performed using Burrows-Wheeler Aligner and identification of somatic mutations was done using LoFreq (version 2) variant caller. The mutations were annotated using an annotation pipeline (VariMAT). Previously published literature and databases were used for the annotation of clinically relevant mutations. The common variants were filtered for reporting based on the presence in various population databases (1000G, ExAC, EVS, 1000Japanese, dbSNP, UK10K, MedVarDb). A custom read-depth-based algorithm was used to determine CNV (Copy Number Variants) from targeted sequencing experiments. Rare CNVs were detected using a comparison of the test data read-depths with the matched reference dataset. Reportable mutations were prioritized and prepared based on AMP-ASCO-CAP (Association for Molecular Pathology-American Society of Clinical Oncology-College of American Pathologists), WHO guidelines, and also based on annotation metrics from OncoMD (a knowledge base of genomic alterations).The informativity of the panel was 95 percent.This study demonstrates the high yield of information in DLBCL using the NGS Lymphoma panel. Results also highlight the molecular heterogeneity of DLBCL subtypes which indicates the need for further studies to make the results of the NGS more clinically relevant.

Aims: To study whether there is any correlation between baseline blood basophil count and serum tryptase levels in newly diagnosed chronic phase chronic myeloid leukemia (CML-CP) patients. Settings and Design: 40 newly diagnosed CML-CP patients were enrolled from Medical Oncology Hematology OPD based on their baseline BCR-ABL status (done in department of Biochemistry). Methods and Materials: Serum tryptase level was measured using Sandwich ELISA and peripheral blood basophil count was estimated using automated cell counter & peripheral blood film examination. BCR-ABL quantification was done using real time PCR after conversion of RNA (extracted from whole blood) to cDNA. Statistical Analysis Used: SPSS Version 23. Results: Baseline peripheral blood basophil levels showed a significant correlation with baseline serum tryptase levels (p

Background: An adverse drug reaction (ADR) is defined by the World Health Organization (WHO) as “Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or therapy”. Cancer chemotherapy is associated with the occurrence of ADRs, which is a worldwide problem. Monitoring and reporting of these ADRs are essential to safeguard the patient and to manage it accordingly. The outcome would create alertness and prevent their recurrence. Hence, we have undertaken a hospital-based study to study the frequency and nature of ADRs due to chemotherapeutic agents. Methods: A total of 500 patients developed ADRs due to cancer chemotherapy from 13th April 2018 to 18th September 2019. Demographics of the patient, drugs taken, and ADRs encountered were recorded in a predesigned form. Results: A total of 665 ADRs were recorded from 500 patients. Anemia was the most common ADR encountered followed by nausea/vomiting and leucopenia. Leukemia (s) were common cancer observed followed by lung and breast cancers. The most common drugs implicated were cisplatin, paclitaxel, carboplatin, and doxorubicin. Naranjo's scale showed 92% of ADRs as probable and 7% as possible. Severity scale showed 80.2% of ADRs were of moderate (level 3 and 4) severity, 11.6% of mild (level 1 and 2) severity, and 8.2% of level 5 severity. A total of 26.8% of ADRs were deemed preventable and 73.2% were not preventable. Conclusions: Our study provides safety data regarding the usage of anti-cancer drugs. Hence, it creates alertness among the treating doctors to prevent its recurrence.

IntroductionChildhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.MethodsProspective cohort study in 109 institutions in 41 countries. Inclusion criteria: children ResultsAll-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3–11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); pConclusionsChildren with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer.

Hb E-β thalassemia is the most common form of hemoglobinopathy in Southeast Asia and eastern India. Iron overload resulting from blood transfusion and increased intestinal iron absorption promotes the formation of reactive oxygen species (ROS), leading to oxidative stress, organ dysfunction, and tissue damage. Of these, cardiovascular complications are the leading cause of mortality. Impaired endothelial function is a biomarker of vascular health in patients with cardiovascular risks. Therefore, assessment of endothelial function is a useful prognostic tool. In the present study, 60 E- β thalassemia patients and 60 healthy, age, sex matched control subjects were taken. The mean hemoglobin and ferritin of thalassemic patients were 7.43gm/dl and 1032 mcg/dl respectively. The vascular health was compared by measuring flow-mediated vasodialation (FMD), arterial elastic parameters, and carotid intima-medial thickness (CIMT). There was lower FMD (7.49%) and higher CIMT (0.46mm) in thalassemic group than control (10.52 % and 0.36mm respectively) (p valuelt; 0.05). Also arterial stiffness is elevated and arterial distensibility is lower in thalassemic patients than control. Among the thalassemic patients FMD or CIMT did not correlate with serum ferritin value. So, the E- β thalassemia patients had poor vascular health and are at a higher risk of developing atherosclerosis and cardio-vascular complication than normal population. The vascular dysfunction does not correlate with serum ferritin value, so regular monitoring with Doppler study is required for early diagnosis of subclinical atherosclerosis in this group of patients. However the effects of chelation therapy, Hydroxyurea, or other targeted therapies needs to be validated by further study.

Human body harbours enormous numbers of microbial organisms, including bacteria, viruses, and fungi which have a momentous role in well-being and illness in humans. Immune system shelters us from pathogenic bacteria, microorganisms found in human tissues have many benefits related to the functional movement of the host by regulating important procedures such as immunity, signalling, and breakdown. Lymphocytes assume a significant part in the reaction to bacterial colonization, primarily by prompting a safe reaction to obstruction or initiation. Most immunologically occupant cells have a place with the mucosal invulnerable framework and are continually motioned by dendritic cells or other Antigen introducing cells that gather intestinal samples. Thus, Microbiome is a key contributor to developing lymphoma and specific alterations to microbiome composition could attenuate the risk. There is an indication that microbial morphology can affect and control humanoids. The difference in the composition of these microorganisms is associated with tumour development. With the increased knowledge of the connection among the human microbiome and carcinogenesis, the use of these findings to prevent, predict or diagnose of lymphomas has attracted a great attention. In this article, we explored current knowledge of various microbial ecosystems, their connection with carcinogens and the potential for useful microorganisms to control and prevent B and T cell lymphoma.

Cryptosporidium infection is usually self-limiting but can be life-threatening in immunocompromised patients. It has emerged as an important cause of diarrhea in such patients worldwide. In this report, we describe a case of Cryptosporidium diarrhea in a child on induction therapy for acute lymphoblastic leukemia (ALL); timely diagnosis using multiplex polymerase chain reaction (PCR) led to definitive treatment and a favorable outcome in our patient.

Thrombotic thrombocytopenic purpura (TTP) which can cause significant mortality is a thrombotic microangiopathy due to deficiency of VWF cleaving protease ADAMTS13 and as per medical literature there are examples that TTP can be caused by COVID 19 infection. A 35 years old female after admission with right sided weakness and slurring of speech was found to be COVID positive and diagnosed as a case of TTP. Patient had absent ADAMTS13 level on day 1. Treatment was started with therapeutic plasma exchange (TPE) later injection Vincristine and Rituximab was given after 4th TPE as it was suspected as refractory case. Finally patient received 16 TPE procedures with cryo poor plasma as exchange fluid and gradually her platelet count started to maintain normal and she was discharged. Specific management and such association of this type of cases need to be studied more judiciously.

While lymphopenia has been a common finding in COVID-19 infection, particularly in severe cases, febrile neutropenia has been very rarely reported in immunocompetent patients with COVID-19. Herein, we report the case of a 76-year-old hypertensive and diabetic man who was hospitalised with severe COVID-19 infection and developed delayed-onset severe neutropenia with neutropenic fever, which responded to treatment with antibiotics and granulocyte colony-stimulating factor. This case highlights the importance of identifying a rare complication (febrile neutropenia on the fifth week) of COVID-19 infection in hospitalised patients by intensive monitoring and aggressive management for favourable outcomes.

Visceral leishmaniasis (VL), also known as kala-azar (black fever in Hindi), is a disease primarily caused by Leishmania donovani. The most important clinical manifestation of visceral leishmaniasis is fever. Nonspecific laboratory findings of visceral leishmaniasis include anemia, neutropenia, eosinopenia, and thrombocytopenia. Definitive diagnosis of visceral leishmaniasis requires the demonstration of either parasite by smear or tissue by culture (usually bone marrow or spleen). Myasthenia gravis is an autoimmune disease caused by antibodies to acetylcholine receptors in the post-junctional membrane of the neuromuscular junction. It typically presents with fatigable muscle weakness without any sensory or brain involvement. It is usually treated with corticosteroids and immunosuppressants like azathioprine. Here we encountered a confirmed case of myasthenia gravis on azathioprine with pancytopenia. While working up to evaluate pancytopenia, bone marrow examination revealed presence of Donovan bodies and the patient showed good response to liposomal amphotericin-B. In retrospect, a case of myasthenia gravis, who presented with pancytopenia presumably drug-induced, was found to have visceral leishmaniasis.

Background Cancer is the second most common cause of deaths worldwide. Likewise, in India, it is a major health problem, and disease burden is escalating every year. Cancer chemotherapy produces unfavorable effects on the well‐being of an individual. Since the past few years, quality of life (QoL) is considered as the main goal of cancer treatment in the survival of a patient. Aim This current study aimed to assess the QoL and factors affecting it in adult cancer patients undergoing chemotherapy treatment. Methods and Results An analytical, cross‐sectional study was conducted to achieve the objectives, employing the consecutive sampling method. A total of 120 adult (>19 years) patients were recruited from daycare chemotherapy unit of a tertiary care hospital. The data were collected using patient record form and Functional Assessment of Cancer Therapy‐General (FACT‐G), a quality of life (QoL) questionnaire. The overall mean score of quality of life (QoL) was 61.933 ± 5.85502. The domains of functional well‐being and emotional well‐being were most negatively affected after cancer chemotherapy. Education (illiteracy) and occupation (unemployment) were negatively associated with overall quality of life (QoL) of cancer patients on chemotherapy. Adverse drug reactions due to cancer chemotherapy negatively affect the quality of life (QoL) of cancer patients. Education (illiteracy) affects social well‐being domain of cancer patients. Working in the government/private sector has a positive impact on functional well‐being domain of quality of life (QoL). Conclusion The study findings suggest an overall low quality of life (QoL) among adult cancer patients undergoing chemotherapy at our setup. It has been identified as a stressful therapy, also affecting both psychological and physical well‐being. Poor infrastructure, illiteracy, poverty, and lack of proper treatment facilities at most centres often lead to poor survival outcomes and hence focus has always been on achieving quantity of life rather than quality of life (QoL). This is further complicated due to nonavailability of validated tools in local vernacular, apathy of the treating physicians in the context of QoL aspects and social and cultural factors that are unique to this society. Psycho‐oncology needs to become an integral entity of comprehensive cancer care.

Background: An anaplastic large cell lymphoma (ALCL) involving the cervical spine and leading to quadriplegia is very rare. Case Description: A 48-year-old immunocompetent male presented with quadriplegia that warranted an anterior cervical corpectomy/fusion. He was previously being presumptively treated for cervical disease attributed to tuberculosis. The histopathology and immunohistochemistry revealed an ALCL that was anaplastic lymphoma kinase (ALK) negative. The patient had a favorable response to surgery followed by CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone) chemotherapy. Conclusion: ALK-negative ALCL presenting with quadriplegia due to primary involvement of cervical spine is extremely rare, but must be diagnosed and appropriately managed.

Dermatology consultation was sought for a 55-year-old man with asymptomatic generalised skin nodules, admitted under haematology for suspected multiple myeloma (MM). On examination, multiple skin-coloured to erythematous to violaceous, shiny, discrete papules and dome-shaped nodules with a firm consistency and waxy smooth feel, measuring 1–5 cm, were seen on the limbs and trunk (figure 1A–G). Dermoscopy revealed a central homogeneous pink area studded with linear and serpiginous vessel network which was accentuated at the periphery forming a rim of vessel network (figure 2A). A 4 mm punch biopsy of cutaneous nodule over the trunk showed diffuse infiltration of the dermis by sheets of plasma cells, including immature, mature and binucleate forms (figure 2B). On immunohistochemistry, the plasma cells were positive for CD138 (figure …

Although Candida albicans remains the predominant species causing Blood Stream Infection (BSI), recent studies have demonstrated an emergence of Non-albicans Candida spp (NAC), such as C. glabrata, C. papapsilosis and C. krusei. Candida krusei are yeast-like microorganisms which may colonise the human skin, respiratory or gastrointestinal tract but can cause lethal infections especially in immunocompromised patients. Hereby, author’s report a case of 10-year-old male with T-cell Acute Lymphocytic Leukaemia (ALL) who reported with fever and non-productive cough caused by Candida krusei. Direct gram stain from blood culture and germ tube test was performed. Further, the isolate was initially misidentified by Matrix Assisted Laser Desorption/Ionisation Time of Flight Mass Spectrometry (MALDI-TOF MS) as Trichosporon ovoides which was later identified by molecular sequencing as Candida krusei.

Chronic activation of B-cell receptor (BCR) signaling via Bruton tyrosine kinase (BTK) is largely considered to be one of the primary mechanisms driving disease progression in B–Cell lymphomas. Although the BTK-targeting agent ibrutinib has shown promising clinical responses, the presence of primary or acquired resistance is common and often leads to dismal clinical outcomes. Resistance to ibrutinib therapy can be mediated through genetic mutations, up-regulation of alternative survival pathways, or other unknown factors that are not targeted by ibrutinib therapy. Understanding the key determinants, including tumor heterogeneity and rewiring of the molecular networks during disease progression and therapy, will assist exploration of alternative therapeutic strategies. Towards the goal of overcoming ibrutinib resistance, multiple alternative therapeutic agents, including second- and third-generation BTK inhibitors and immunomodulatory drugs, have been discovered and tested in both pre-clinical and clinical settings. Although these agents have shown high response rates alone or in combination with ibrutinib in ibrutinib-treated relapsed/refractory(R/R) lymphoma patients, overall clinical outcomes have not been satisfactory due to drug-associated toxicities and incomplete remission. In this review, we discuss the mechanisms of ibrutinib resistance development in B-cell lymphoma including complexities associated with genomic alterations, non-genetic acquired resistance, cancer stem cells, and the tumor microenvironment. Furthermore, we focus our discussion on more comprehensive views of recent developments in therapeutic strategies to overcome ibrutinib resistance, including novel BTK inhibitors, clinical therapeutic agents, proteolysis-targeting chimeras and immunotherapy regimens.