Amine-decorated Zirconium Based Metal Organic Framework for Ultrafast Detection of 2,4,6-Trinitrophenol in Aqueous Samples.

An amine-decorated zirconium based metal organic framework (MOF) UiO-66-NH2 with rod shape morphology was synthesized by solvothermal process using 2-aminoterephthalic acid as an organic linker. Crystallinity of synthesized MOF material was confirmed with PXRD technique. MOF was employed as selective and sensitive sensor for ultra-trace detection of 2,4,6-trinitrophenol (TNP) in aqueous matrix, even in coexistence with other competitive nitroaromatic analytes. High value of Stern-Volmer quenching constant Ksv (1.106 × 105 M- 1), plausible photoluminescent quenching efficiency (97.8%) and lower detection limit (0.95 µM/217ng mL- 1) ascertained extraordinary sensitivity of developed MOF for TNP. Density functional theory calculations and electrostatic interactions (i.e. ionic interaction, H-bonding and π-π interaction) indicated that electron and energy transfer processes play a key role in turn-off quenching response of UiO-66-NH2 sensor. Spiked real samples were analysed to validate the developed method, which satisfactorily established the developed MOF sensor as an efficient tool for analysis.

Efficient Turn-On Zr Based Metal Organic Framework Fluorescent Sensor for Ultrafast Detection of Danofloxacin in Milk Samples.

Metal organic framework, UiO-67 was synthesized by coordinating Zr(IV) with 4,4'-biphenyldicarboxylic acid (BPDC) ligand. Morphology and crystallinity of MOF was confirmed with FE-SEM and PXRD procedure. Danofloxacin (DANO), a veterinary fluoroquinolone antibiotic, was detected in milk by employing UiO-67 as "turn-on" fluorescent sensor. Original photoluminescent (PL) efficiency of UiO-67 sensor was enhanced on its electronic interaction with DANO molecule. Significant PL efficiency enhancement, lower detection limit 0.49 ng/mL (1.37 nM), swift detection (time < 1 min), and excellent linear correlation (R2 = 0.9988) indicated extraordinary sensitivity of developed UiO-67 sensor for DANO. Selectivity and performance of sensor was unaltered in presence of interfering species and detection results were obtained under permissible variation limits. Method applied successfully for ultra-trace detection of DANO residues in milk samples.

COVID 19 infection associated with thrombotic thrombocytopenic purpura.

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.

Evaluation of multiparametric flow cytometry in diagnosis & prognosis of myelodysplastic syndrome in India.

Background & objectives: Diagnosis of myelodysplastic syndromes (MDS) is subjective in low-grade cases with <5 per cent blasts or <15 per cent ring sideroblasts. Flow cytometry (FCM) has been used to diagnose MDS; but, it still has only an adjunctive role. This study was conducted to evaluate the role of FCM to diagnose MDS and correlate the number of aberrancies with revised international prognostic scoring system (R-IPSS). Methods: This study included 44 consecutive clinically suspected cases of MDS with refractory cytopenia(s) and 10 controls. Patients were divided into two groups: (i) proven MDS cases (n=26), and (ii) suspected MDS (n=18). Ogata quantitative approach, pattern analysis and aberrant antigen expression were studied. Results: Ogata score ≥2 correctly diagnosed 80.7 per cent (21/26) while aberrant antigen and pattern analysis with flow score of ≥3 could diagnose 92.3 per cent (24/26) patients with proven MDS. Combination of both with flow score ≥3 could diagnose 100 per cent patients. Eight patients in suspected MDS group with persistent cytopenia on follow up were labelled as probable MDS. Ogata score ≥2 was present in 5 of 8 and pattern analysis score ≥3 was present in six probable MDS patients. Combination of both with flow score ≥3 was present in seven of eight patients. Spearman's correlation between Ogata score and R-IPSS, pattern analysis and R-IPSS and combination of both scores and R-IPSS showed significant positive correlation in proven MDS as well as when proven and probable MDS patients were combined. Interpretation & conclusions: Our results showed that combined Ogata approach and pattern analysis, demonstration of ≥3 aberrancies in >1 cell compartment could diagnose most MDS patients. Patients with high flow scores had high R-IPSS scores. Patient with flow score ≥3 and borderline cytomorphology should be observed closely for the development of MDS.

Development of a microextraction by packed sorbent with gas chromatography-mass spectrometry method for quantification of nitroexplosives in aqueous and fluidic biological samples.

A new method for quantification of 12 nitroaromatic compounds including 2,4,6-trinitrotoluene, its metabolites and 2,4,6-trinitrophenyl-N-methylnitramine with microextraction by packed sorbent followed by gas chromatography and mass spectrometric detection in environmental and biological samples is developed. The microextraction device employs 4 mg of C18 silica sorbent inserted into a microvolume syringe for sample preparation. Several parameters capable of influencing the microextraction procedure, namely, number of extraction cycles, washing solvent, volume of washing solvent, elution solvent, volume of eluting solvent and pH of matrix, were optimized. The developed method produced satisfactory results with excellent values of coefficient of determination (R2  > 0.9804) within the established calibration range. The extraction yields were satisfactory for all analytes (> 89.32%) for aqueous samples and (> 87.45%) for fluidic biological samples. The limits of detection values lie in the range 14-828 pg/mL.

A Single-Centre Experience of First-Line Romiplostim and Immunosuppressive Therapy in Patients With Aplastic Anemia.

Background Romiplostim, a thrombopoietin (TPO) receptor antagonist, promotes tri-lineage hematopoiesis in patients with acquired aplastic anemia (AA). However, its efficacy as a first-line treatment in combination with an immunosuppressant, i.e., anti-thymocyte globulin (ATG) and cyclosporine (CSA), remains unexplored. Objective To assess the efficacy and safety of romiplostim in combination with ATG and CSA as first-line treatment in patients with AA. Method A single-center, retrospective study of AA patients, where data of patients administered with ATG + CSA + romiplostim as a first-line treatment was included. Romiplostim 5 µg/kg weekly for one month; post that, the dose was increased to 10 µg/kg weekly for the next five months. The primary outcome involves the overall response rate and hematological response at baseline, three months, and six months. Result Data from 12 patients with a median age of 18 years was evaluated. At a median follow-up of six months, 25% achieved a complete response, 41.6% achieved a partial response, and 16.7% had no response. Improvement in tri-lineage hematopoietic response had been seen at six months from baseline, with improvement in absolute neutrophil count (ANC) and platelet count (PC) being the most significant, with an increase of >100% from baseline, followed by total leukocyte count (TLC) (75.13%) and hemoglobin (Hb) (66.07%) from baseline. Two deaths were reported during the treatment. Conclusion Romiplostim, in combination with ATG plus CSA, demonstrated clinically significant outcomes as a first-line treatment in patients with AA. Further studies are required to confirm these findings in larger populations to assess long-term outcomes.

A Comprehensive Review on Metal Organic Framework Based Preconcentration Strategies for Chromatographic Analysis of Organic Pollutants.

Organic pollutants (OPs) are of worldwide concern for being hazardous to human existence and natural flora and fauna in view of their contaminating nature, bio-aggregation properties and long range movement abilities in environment. Metal organic frameworks (MOFs) are a new kind of crystalline porous material, composed of metal ions and multi dentate organic ligands with well-defined co-ordination geometry exhibiting promising application respect to adsorptive evacuation of OPs for chromatographic analysis. Applications of MOFs as preconcentration material and column packing material are reviewed. Key analytical characteristics of MOF based preconcentration techniques and coupled chromatographic procedures are summarized in detail. MOF based preconcentration strategies are compared with conventional sorbent based extraction techniques for thorough evaluation of performance of MOF materials.

Hepatic Plasmacytoma With DEL13q14 Positive on Fluorescent In Situ Hybridization (FISH) on Tissue Biopsy.

A 40-year-old male presented with abdominal distension and dyspnea. On evaluation found to have hepatic plasmacytoma without marrow clonal plasma cells. Fluorescent in situ hybridization (FISH) on tissue biopsy revealed myeloma-defining cytogenetics. After treating with novel agents, the patient had a complete response to therapy.

Audit of In-Hospital Mortality from a Medical Oncology and Hemato-Oncology Center with the Emphasis on Best Supportive Care.

Deepak SundriyalBackground and Objectives The newly established medical oncology and hemato-oncology center at the All India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand, India, provided us an opportunity to audit in-hospital mortalities with a vision that the audit will serve as a standard for ceaseless improvement. Aim of the study was to initiate a vigorous process for the evaluation of all-cause mortality in patients suffering from cancer. Methods An audit of all in-hospital deaths that occurred during the year 2019 was performed, and comprehensive scrutiny of various parameters (demographic, clinico-pathological, therapeutic, causes of death) was done. Reviews from two independent observers sharpened the infallibility of the audit. The lacunae in the existing practices and the scope for further improvement were noted. Results Forty-five in-hospital deaths were registered during the study period (January-December 2019). The majority of the deaths occurred in patients with advanced stage of malignancy ([ n = 31] 68.8%). Most common causes of death were progressive disease, neutropenic, and non-neutropenic sepsis. Chemotherapeutic agents, growth factors, blood components, and antibiotics were found to be used judiciously as per institutional policy. The reviewers emphasized on the use of comorbidity indexes in the treatment planning and avoiding intensive care unit referrals for patients receiving best supportive care (BSC). Emphasis was put on providing only BSC to the patients with a very limited life expectancy. Emphasis was also laid down on record of out of the hospital deaths. Interpretation and Conclusion The audit disclosed areas of care which require further improvement. The mortality audit exercise should become a regular part of evaluation and training for the ongoing and future quality commitment. This should impact the clinical decision making in an oncology center providing quality care to the terminally ill patients.

Next-Generation Sequencing Highlights of Diffuse Large B-cell Lymphoma in a Tertiary Care Hospital in North India.

INTRODUCTION: 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. METHODS: The study included 20 patients having DLBCL. The quality and quantity of tumor cells were accessed by H&E 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). RESULTS: The informativity of the panel was 95 percent. NOTCH 1 was the most frequently mutated gene in 16.1% of patients followed by 12.9% who had ARID1A mutations. MYD88 and TP53 mutations were detected in 9.6% of the patient while 6.4% of patients had CSF3R mutations. NOTCH 1 and TP 53 are the most frequently reported gene in the middle age group (40-60). Mutation in MYD88 is reported in every age group. MYD88 (51%) is the most common mutation in ABC subtypes of DLBCL, followed by NOTCH 1 (44%) and SOCS 1 (33%) according to our findings. NOTCH 1 mutations are frequent in ABC and PMBL subtypes. Closer investigation reveals missense mutation is the most frequent mutation observed in the total cohort targeting 68.4% followed by frameshift deletion reported in 26.3%. Six novel variants have been discovered in this study. CONCLUSIONS: 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.

Visceral leishmaniasis masquerading as drug-induced pancytopenia in myasthenia gravis.

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.

Determination of norfloxacin and enrofloxacin by solid-phase microextraction/high-performance liquid chromatography.

A solid-phase microextraction (SPME) method followed by separation with high-performance liquid chromatography and subsequent UV detection was developed for the determination of norfloxacin and enrofloxacin. The simple and sensitive preconcentration technique uses 280 nm wavelength in mobile phase of citrate buffer (0.01 M), pH 3.8, prepared in water (A) and acetonitrile (B), with composition of the mobile phase A:B, 40:60, at a flow rate of 1.0 mL/min. A C18 reversed-phase analytical column (5 microm) was selected as separation medium for the technique. To obtain optimum extraction efficiency, several parameters relating to SPME were investigated. The method was linear over the range of 10-100 ng/mL for norfloxacin and enrofloxacin with a correlation coefficient (R2) value of 0.9972 and 0.9980 for norfloxacin and enrofloxacin, respectively. Using the SPME method, the detection limits (signal-to-noise ratio = 3) are 0.17 and 0.12 ng/mL for norfloxacin and enrofloxacin, respectively.