Prevalence and clinicopathological features of driver gene mutations profile in BCR: ABL1 negative classical myeloproliferative neoplasm-A single-center study from North India.

BACKGROUND: Recurrent somatic mutations in the JAK2, CALR, and the MPL genes are noted in BCR: ABL1 negative classic myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). MATERIALS AND METHODS: Mutation profile and clinical features of MPN cases diagnosed at a tertiary care center in North India are being described. JAK2V617F mutation was screened using ARMS PCR, and CALR mutation was screened using allele-specific PCR followed by fragment analysis. MPL and JAK2 Exon 12 mutations were screened by Sanger sequencing. Some of the samples were also screened using commercial kits based on single-plex RT PCR. RESULTS: A total of 378 cases (including 124 PV, 121 ET, and 133 PMF cases) were screened over 6.5 years. JAK2V617F mutation was noted in 90.3%, 61.1%, and 69.2% of cases of PV, ET, and PMF, respectively. In PV, JAK2V617F wild-type cases were associated with a significantly lower age (44 yrs vs 54 yrs; P = 0.001), lower TLC (6.3 vs 16.9; P = 0.001), and a lower platelet count (188 × 109/L vs 435 × 109/L; P = 0.009) as compared to the JAK2V617F mutated cases. CALR and MPL mutations were noted in 17.4% and 12% and 0.8% and 5.3% of ET and PMF cases, respectively. Type 1 CALR mutations were commoner in both ET and PMF. The triple negative cases constituted 20.7% and 13.5% cases of ET and PMF, respectively. In ET, the triple negative cases were found to have a significantly lower median age of presentation (42 yrs vs 52 yrs; P = 0.001), lower median TLC (10.2 × 109/L vs 13.2 × 109/L; P = 0.024), and a higher median platelet count (1238 × 109/L vs 906 × 109/L; P = 0.001) as compared to driver genes mutated cases. In PMF, the triple negative cases were found to have a significantly lower hemoglobin level (7.9 g/dl vs 11.0 gl/dl; P = 0.001) and a significant female preponderance (P = 0.05) as compared to the mutated cases. CALR mutations were found to have a significantly lower median age (43 yrs vs 56 yrs; P = 0.001) and lower hemoglobin (9.6 g/dl vs 11.3 g/dl) as compared to the JAK2 mutations. CONCLUSION: Our data on the driver gene mutational profile of BCR: ABL1 negative MPN is one of the largest patient cohorts. The prevalence and clinicopathological features corroborate with that of other Asian studies.

Seroprevalence with epidemiological determinants of hepatitis C virus and Treponema pallidum infection in blood donors of a teaching hospital in southwest Punjab, India: A 5-year study.

Background: A high seroprevalence of various transfusion-transmitted infections (TTIs) in donated blood is the main safety concern, especially in low- and middle-income countries. As per the World Health Organization (WHO) recommendation, all blood donations must be tested for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum infection, and malaria, which mainly comprises the major bulk of TTIs. Aims: The purpose of this study is to observe the seroprevalence of hepatitis C virus and Treponema pallidum infection over the period of 5 years in blood donors of our blood center along with their epidemiological determinants with respect to age, sex, residence, occupation, and type of donors. Materials and Methods: Retrospective study was conducted for the period of 5 years, from 1st January 2017 to December 2021, estimating the seroprevalence of hepatitis C and Treponema pallidum infection in the blood donors along with their epidemiological determinants. Results: Out of 19,689 donations in 5 years, 690 (3.50%) units were positive for transfusion-transmissible infections with 1.67% donors seropositive for HCV, 1.23% for Treponema pallidum infection, 0.42% for HBV, and 0.18% for HIV. The prevalence of TTIs was found to be highest in 2020 (4.52%) and least in 2017 (2.57%). Out of a total of 330 HCV cases detected in 5 years, 84.85% of cases were seen in voluntary donors. Rural donors constituted 71.21% of cases. The majority of cases were seen in the age group of 18-30 years, i.e., 61.82%, and a maximum number of cases were seen in the farmers (31.21%), followed by laborers and construction workers (21.21%). Out of a total of 242 cases of Treponema pallidum infection, 84.29% were seen in voluntary blood donors. Demographic data showed 70.24% of cases in rural donors. Occupational data revealed a maximum number of cases in farmers (34.29%), followed by laborers (21.90%). Conclusion: Higher seroprevalence of HCV and Treponema pallidum infection in our region as compared with other areas is a matter of great concern about the growing infection rate of these in our area. Stringent use of donor selection criteria and more vigorous donor screening is utmost need of the hour for reducing the burden of TTIs in blood transfusion services.

A Rapid Method for Determination of Serum Methotrexate Using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application in Therapeutic Drug Monitoring.

Objectives Methotrexate (MTX) has anticancer therapeutic potential with multiple doses-related adverse effects and toxicities. Immunoassays for therapeutic monitoring of serum MTX have their own limitations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is considered as the reference method; however, commercially availability of them is limited. We aimed to adapt/develop an in-house LC-MS/MS method for therapeutic monitoring of serum MTX. Materials and Methods Serum protein precipitation was performed using acetonitrile-water containing 250 µM solution of aminoacetophenone as internal standard (IS). Chromatographic separation was achieved on a C18 column with mobile phase of 0.1% solution of formic acid (solvent A) and acetonitrile (solvent B) at a flow rate of 0.4 mL/min. MS was performed under positive ion mode with mass transition for MTX and IS as m/z 455.1→308.1 and 136.2→94.1, respectively. The method was validated by following Bioanalytical Method Validation Guidance for Industry, 2018 and applied on leukemia patients' samples on MTX therapy. Results The correlation coefficient of eight serially diluted calibration standards of 0.09 to 12.5 µM was >0.99 and had linearity with > 95% precision and accuracy at analytical quality control levels. The lower limit of MTX quantification achieved was 0.09 µM with good intensity and sharp peak as compared with blank sample. The total run time of the assay was 5 minutes. The serum MTX levels obtained by this method in leukemia patients exhibited clinical correlation and an excellent agreement with commercial immunoassay used in parallel. Conclusion We were able to develop a rapid, sensitive, and cost-effective LC-MS/MS method suitable for therapeutic drug monitoring of MTX in routine clinical diagnostic laboratories.

Potential of Rhodosporidium toruloides for Fatty Acids Production Using Lignocellulose Biomass.

Microbial lipids are ideal for developing liquid biofuels because of their sustainability and no dependence on food crops. Especially the bioprocess for microbial lipids may be made economical by using sustainable approaches, e.g., lignocellulose-based carbon sources. This demand led to a search for ideal microorganisms with the ability to utilize efficiently biomass into value-added products. Rhodosporidium toruloides species belongs to the family of oleaginous (OG) yeast, which aggregates up to 70% of its biomass to produce fatty acids which can be converted to a variety of biofuels. R. toruloides is extremely adaptable to different types of feedstocks. Among all feedstock, a lot of effort is going on to develop a bioprocess of fatty acid production from lignocellulose biomass. The lignocellulose biomass is pretreated using harsh conditions of acid, alkali, and other which leads to the generation of a variety of sugars and toxic compounds. Thus, so obtained lignocellulose hydrolysate may have conditions of different pH, variable carbon and nitrogen ratios, and other non-optimum conditions. Accordingly, a detailed investigation is required for molecular level metabolism of R. toruloides in response to the hydrolysate for producing desired biochemicals like fatty acids. The present review focuses on numerous elements and obstacles, including metabolism, biofuel production, cultivation parameters, and genetic alteration of mutants in extracting fatty acids from lignocellulosic materials utilizing Rhodosporidium spp. This review provides useful information on the research working to develop processes for lignocellulose biomass using oleaginous yeast.

Neoadjuvant chemotherapy with or without anthracyclines in combination with single HER2-targeted therapy in HER2-positive breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with human epidermal growth factor receptor 2 (HER2) blockade is the preferred approach for treating early and locally advanced HER2-positive breast cancer. There is a lack of robust data comparing pathological complete response (pCR) and survival outcomes in anthracycline-free and anthracycline-containing regimens with single HER2-targeted therapy. OBJECTIVES: The present study retrospectively evaluated pCR between two groups: Single HER2-targeted therapy with and without anthracycline. METHODS: A total of 215 HER2-positive female breast cancer patients were analyzed who received eitheranthracycline-containing EC-TH (epirubicin and cyclophosphamide, followed by docetaxel and trastuzumab)oranthracycline-free TCH [docetaxel, carboplatin and trastuzumab]. Univariate and multivariate analyses identified prognostic factors for survival and pCR.Kaplan Meier survival curvesdetermined disease-free survival(DFS) and overall survival (OS). RESULTS: Baseline characteristics were comparable in both treatment groups. The pCR rate was 30.8% in the anthracycline-containing EC-TH group and 40.9% in the anthracycline-free TCH group; p = 0.140. Disease-free survival at 3 years (65.8% vs. 58.4%) and 5 years (49.2% vs. 55.2%) was similar between EC-TH and TCH groups, respectively (log-rank p = 0.550). Three-year (95.5% vs. 92.5%) and five-year (84.4% vs. 80.8%) OSwere also comparable between both groups (log-rank p = 0.485). The anthracycline-containing EC-TH group had a higher incidence of febrile neutropenia (6.4%. vs. 3.6%) and cardiac adverse events (7.7% vs. 4.4%) than the anthracycline-free TCH group. CONCLUSION: Neoadjuvant anthracycline-free chemotherapy has similar pCR and survival outcomeswith favourable cardiac and non-cardiac adverse effect profiles compared with anthracycline-containing chemotherapy.

COVID-19 infected ST-Elevation myocardial infarction in India (COSTA INDIA).

OBJECTIVE: To find out differences in the presentation, management and outcomes of COVID-19 infected STEMI patients compared to age and sex-matched non-infected STEMI patients treated during the same period. METHODS: This was a retrospective multicentre observational registry in which we collected data of COVID-19 positive STEMI patients from selected tertiary care hospitals across India. For every COVID-19 positive STEMI patient, two age and sex-matched COVID-19 negative STEMI patients were enrolled as control. The primary endpoint was a composite of in-hospital mortality, re-infarction, heart failure, and stroke. RESULTS: 410 COVID-19 positive STEMI cases were compared with 799 COVID-19 negative STEMI cases. The composite of death/reinfarction/stroke/heart failure was significantly higher among the COVID-19 positive STEMI patients compared with COVID-19 negative STEMI cases (27.1% vs 20.7% p value = 0.01); though mortality rate did not differ significantly (8.0% vs 5.8% p value = 0.13). Significantly lower proportion of COVID-19 positive STEMI patients received reperfusion treatment and primary PCI (60.7% vs 71.1% p value=< 0.001 and 15.4% vs 23.4% p value = 0.001 respectively). Rate of systematic early PCI (pharmaco-invasive treatment) was significantly lower in the COVID-19 positive group compared with COVID-19 negative group. There was no difference in the prevalence of high thrombus burden (14.5% and 12.0% p value = 0.55 among COVID-19 positive and negative patients respectively) CONCLUSIONS: In this large registry of STEMI patients, we did not find significant excess in in-hospital mortality among COVID-19 co-infected patients compared with non-infected patients despite lower rate of primary PCI and reperfusion treatment, though composite of in-hospital mortality, re-infarction, stroke and heart failure was higher.

Amelioration of the physio-biochemical responses to salinity stress and computing the primary germination index components in cauliflower on seed priming.

The significant horticultural crop, cauliflower (Brassica oleracea L. var. botrytis) is vulnerable to the excessive salt concentration in the soil, which contributes to its scaled-down growth and productivity, among other indices. The current study examines the efficacy of hydropriming, halopriming, and osmopriming on the physio-biochemical attributes and tolerance to salinity (100 mM NaCl) in cauliflower under controlled conditions. The results showed that the salinity (100 mM NaCl) has significant deleterious impacts on cauliflower seed germination, seedling growth, and photosynthetic attributes, and provoked the production of reactive oxygen species. In contrast, different priming approaches proved beneficial in mitigating the negative effects of salinity and boosted the germination, vigor indices, seedling growth, and physio-biochemical attributes like photosynthetic pigments, protein, and proline content while suppressing oxidative damage and MDA content in cauliflower seedlings in treatment- and dose-dependent manner. PCA revealed 61% (PC1) and 15% (PC2) of the total variance with substantial positive relationships and high loading conditions on all germination attributes on PC1 with greater PC1 scores for PEG treatments showing the increased germination indices in PEG-treated seeds among all the priming treatments tested. All 13 distinct priming treatments tried clustered into three groups as per Ward's approach of systematic categorization, clustering the third group showing relatively poor germination performances. Most germination traits exhibited statistically significant associations at the p < 0.01 level. Overall, the results established the usefulness of the different priming approaches facilitating better germination, survival, and resistance against salinity in the cauliflower to be used further before sowing in the salt-affected agro-ecosystems.

Role of T Lymphocyte Activation Profile in Predicting SARS-CoV-2 Severity: Experience from Tertiary Care Centre of North India.

Background: Immune dysregulation plays a key role in determining COVID-19 disease severity. We aimed to analyze the T cell activation profile in COVID - 19 cases and its predictive role in disease severity and outcome. Material & methods: This was a prospective observational pilot study from a tertiary care COVID-19 hospital. Peripheral blood samples obtained between the fifth and seventh day of COVID-19 illness, were subjected to lymphocyte subset analysis using multicolor flowcytometry using a single tube, 8 antibodies (CD45, CD19, CD3, CD4, CD8, CD38, HLADR, and CD56) analysis. Correlation between lymphocyte subset analysis and clinical profile was determined. Results: 26 patients including 11 with mild disease and 15 with severe disease were enrolled. The median age was 58 years (range: 33-81), with a male: female ratio of 1.36:1. Significant lymphopenia was observed in the severe group compared to the mild group (p < 0.02). The absolute numbers of CD3+, CD4+, CD8 + T cells, B cells, and NK cells were significantly reduced in the severe group as compared to the mild group (p < 0.05). In patients with severe disease, the proportion of CD8 + and CD4 + T cells were significantly higher than those in patients with mild disease (p = 0.0372). Using ROC analysis, a CD4:8 T cell ratio of ≥ 2.63 and an activated (CD38 + HLA-DR+) CD8 T cell proportion of > 15.85% of the total CD8 T cell population, significantly determined the severe disease category. Conclusions: Severe COVID-19 is associated with severe lymphopenia, altered CD4/CD8 ratio and markedly increased CD8 T cell activation profile. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01558-6.

Upfront Screening by Quantitative Real-Time PCR Assay Identifies NUP98::NSD1 Fusion Transcript in Indian AML Patients.

NUP98::NSD1 fusion, a cryptic translocation of t(5;11)(q35;p15.5), occurs predominantly in pediatric AML, having a poor prognostic outcome. There are limited studies on the diagnosis of NUP98::NSD1 fusion in a clinical setting, and most of the data are from Western countries. No study on the detection of this translocation has been reported from the Indian subcontinent to date. One possible reason could be the lack of availability of a potential tool to detect the fusion transcript. We have developed a real-time quantitative PCR (qRT-PCR)-based assay to detect NUP98::NSD1 fusion transcript with high sensitivity and specificity. Screening 150 AML patients (38 pediatric and 112 adults) using the assay showed the presence of fusion transcript in six patients including 03 pediatric, and 03 adult patients. We observed a prevalence rate of 7.89% (3/38) and 2.67% (3/112) fusion transcript in pediatric and adult patients, respectively. Sanger sequencing further validated the occurrence of NUP98::NSD1 fusion in all six patients. Molecular characterization of these patients revealed a co-occurrence of FLT3-ITD mutation, accompanied by altered expression of the HOX and other genes associated with AML. All six patients responded poorly to induction therapy. Overall, this is the first study to show the presence of the NUP98::NSD1 fusion transcript in Indian AML patients. Further, we demonstrate that our in-house developed qRT-PCR assay can be used to screen NUP98::NSD1 fusion in clinical settings.

An Analysis of M-protein in Plasma cell Dyscrasia Patients Identifies that IgG Lambda Subtype is More Commonly Associated with Normal Serum Free Light Chain (SFLC) Ratio.

The determination of monoclonal protein (M-protein) by SPE, IFE and SFLC assay is fundamental in the diagnosis of Plasma cell proliferative disorder (PCPD). In the present study, we seek to assess the diagnostic performance and concordance of these three techniques in un-treated PCPD patients. All new patients with dysproteinemia and/or suspected PCPD were included in this retrospective observational study. The baseline parameters were retrieved from electronic medical records. SPE was performed on gel electrophoresis system; monoclonal component was identified by IFE. SFLC assays were performed by nephelometry using a latex-enhanced immunoassay. Total 402 patients of PCPD were included (10.9% of MGUS/SMM and 89.1% of multiple myeloma). The combination of SPE + rSFLC (ratio of kappa/lambda light chain) and SPE + IFE + rSFLC was able to detect M-protein across all subgroups of patients. In 61 patients, rSFLC values were within normal range (54.5% of MGUS/SMM and 10.3% of MM) and was more commonly seen with IgG lambda M-protein (57.4% vs. all-others). The median dFLC value, among these patients, was higher for MM than MGUS/SMM patients (23.8 vs. 14.4 mg/L, respectively). The combination of SPE and rSFLC can be reliably used to detect M-protein in PCPD patients. In a small subgroup of MM patients, despite the presence of an intact immunoglobulin (M-protein), the rSFLC is not abnormal. Historically, these patients should respond better to treatment. However, a further follow-up analysis with more number of such patients would be advantageous for better understanding.

Cytochrome C as a potential clinical marker for diagnosis and treatment of glioma.

Gliomas are the most prevalent kind of malignant and severe brain cancer. Apoptosis regulating mechanisms are disturbed in malignant gliomas, as they are in added forms of malignancy. Understanding apoptosis and other associated processes are thought to be critical for understanding the origins of malignant tumors and designing anti-cancerous drugs for the treatment. The purpose of this study was to evaluate the variation in the expression level of several apoptotic proteins that are responsible for apoptosis in low to high-grade glioma. This suggests a significant change in the expression of five apoptotic proteins: Clusterin, HSP27, Catalase, Cytochrome C, and SMAC. Cytochrome C, one of the five substantially altered proteins, is a crucial component of the apoptotic cascade. The complex enzyme Cytochrome C is involved in metabolic pathways such as respiration and cell death. The results demonstrated that Cytochrome C expression levels are lower in glioma tissues than in normal tissues. What's more intriguing is that the expression level decreases with an increase in glioma grades. As a result, the discovery shows that Cytochrome C may be a target for glioma prognostic biomarkers.

Acute lymphoblastic leukemia masquerading as hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a condition characterized by immunological imbalance due to inappropriate activation of macrophage, T/NK cells resulting in hypercytokinemia and subsequent tissue damage. We present an interesting case of acute lymphoblastic leukemia (ALL) who presented to us with clinical and laboratory features of HLH. High index of suspicion for malignancy based on clinical history and bone marrow examination led us to reach at definitive diagnosis of ALL.

New insights into development and mortality of COVID-19-associated pulmonary aspergillosis in a homogenous cohort of 1161 intensive care patients.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real-world insights about the disease. METHODS: We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non-CAPA and deceased/survived CAPA patients using univariable and multivariable models. RESULTS: The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non-CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1-2.8]). Diabetes (odds ratio [OR] 1.92 [1.15-3.21]); persistent fever (2.54 [1.17-5.53]); hemoptysis (7.91 [4.45-14.06]); and lung lesions of cavitation (8.78 [2.27-34.03]), consolidation (9.06 [2.03-40.39]), and nodules (8.26 [2.39-28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09-6.55]), a high computed tomography score index (OR 1.18 [1.08-1.29]; p < .001), and pulse glucocorticoid treatment (HR 4.0 [1.3-9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03-1.15] and mortality: 1.17 [1.08-1.28]) and lymphopenia (development: 0.68 [0.51-0.91] and mortality: 0.40 [0.20-0.83]) were associated with the development as well as mortality of CAPA. CONCLUSION: We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality.

Prognostic Role of Interim 18-Fluorodeoxyglucose-PET in Diffuse Large B Cell Lymphoma: Experience from a Tertiary Care Centre in North India.

This study was done to investigate the role of Interim 18-FDG-PET/CT (i-PET) in predicting the outcome of Diffuse Large B Cell Lymphoma (DLBCL) patients. The Lymphoma registry data base of the Department of Haematology was reviewed for all newly diagnosed DLBCL patients treated with R-CHOP-21 (n = 63). The PET-CT data of these patients at pre-defined time points (baseline, interim and end of treatment) was systematically collected. The predictive accuracy of i-PET-CT (done after 4 cycles R-CHOP-21 chemotherapy) was analysed to define their prognostic importance. 47 patients were eligible for final analysis in this study. According to Deauville's criteria 15 patients (31%) were positive on i-PET. The positive predictive value (PPV) of i-PET by DS was 73.3%. At a median follow up of 21 months, DS based i-PET negative and positive cases showed significant differences in 2-year OS (81.2% vs 46.7%, p = 0.007) and PFS (75% vs 26.7%, p = 0.005). Combined analysis of i-PET (by DS) and IPI showed negative predictive value (NPV) of 92.3% in Low IPI while PPV of 76.9% in high IPI subgroup of DLBCL. On a multivariate analysis of all prognostic variables, i-PET was found to be independent prognostic marker predicting outcome in DLBCL patients. i-PET is an independent prognostic marker for outcome in DLBCL patients. Combined analysis of Interim PET along with IPI score at diagnosis improves the predictive accuracy of i-PET (both PPV & NPV) and may guide tailoring of therapy in these patients.

Nano Matrix Soft Confectionary for Oral Supplementation of Vitamin D: Stability and Sensory Analysis.

Vitamin D deficiency distresses nearly 50% of the population globally and multiple studies have highlighted the association of Vitamin D with a number of clinical manifestations, including musculoskeletal, cardiovascular, cerebrovascular, and neurological disorders. In the current study, vitamin D oil-in-water (O/W) nanoemulsions were developed and incorporated in edible gummies to enhance bioavailability, stability, and patient compliance. The spontaneous emulsification method was employed to produce a nano-emulsion using corn oil with tween 20 and lecithin as emulsifiers. Optimization was carried out using pseudo-ternary phase diagrams and the average particle size and polydispersity index (PDI) of the optimized nanoemulsion were found to be 118.6 ± 4.3 nm and 0.11 ± 0.30, respectively. HPLC stability analysis demonstrated that the nano-emulsion prevented the degradation and it retained more than 97% of active vitamin D over 15 days compared to 94.5% in oil solution. Similar results were obtained over further storage analysis. Vitamin D gummies based on emulsion-based gelled matrices were then developed using gelatin as hydrocolloid and varying quantities of corn oil. Texture analysis revealed that gummies formulated with 10% corn oil had the optimum hardness of 3095.6 ± 201.7 g on the first day which remained consistent on day 45 with similar values of 3594.4 ± 210.6 g. Sensory evaluation by 19 judges using the nine-point hedonic scale highlighted that the taste and overall acceptance of formulated gummies did not change significantly (p > 0.05) over 45 days storage. This study suggested that nanoemulsions consistently prevent the environmental degradation of vitamin D, already known to offer protection in GI by providing sustained intestinal release and enhancing overall bioavailability. Soft chewable matrices were easy to chew and swallow, and they provided greater patient compliance.

Intranasal Cerium Oxide Nanoparticles Ameliorate Cognitive Function in Rats with Alzheimer's via Anti-Oxidative Pathway.

Cerium oxide nanoparticles (CNPs), owing to their antioxidant property, have recently emerged as therapeutic candidate for Alzheimer's disease (AD). However, intravenous CNPs are limited due to their poor physicochemical properties, rapid blood clearance and poor blood-brain penetration. Thus, we developed intranasal CNPs and evaluated its potential in experimental AD. CNPs were synthesized using homogenous precipitation method and optimized through Box-Behnken Design. The formation of CNPs was confirmed by UV spectroscopy and FTIR. The optimized CNP were spherical, small (134.0 ± 3.35 nm), uniform (PDI, 0.158 ± 0.0019) and stable (ZP, -21.8 ± 4.94 mV). The presence of Ce in CNPs was confirmed by energy-dispersive X-ray analysis. Further, the X-ray diffraction spectra revealed that the CNPs were nano-crystalline. The DPPH assay showed that at concentration of 50 µg/mL, the percentage radical scavenging was 95.40 ± 0.006%. Results of the in vivo behavioral studies in the scopolamine-induced Alzheimer rat model showed that intranasal CNPs dose dependently reversed cognitive ability. At dose of 6 mg/kg the morris water maze results (escape latency, path length and dwell time) and passive avoidance results (retention latency) were significantly different from untreated group but not significantly different from positive control group (rivastigmine patch, 13.3 mg/24 h). Further, biochemical estimation showed that intranasal CNP upregulated the levels of SOD and GSH in brain. In conclusion, intranasal CNPs, through its antioxidant effect, could be a prospective therapeutics for the treatment of cognitive impairment in AD.

Transient left ventricular dysfunction after therapeutic pericardiocentesis - Takotsubo cardiomyopathy or pericardial decompression syndrome.

We present a case of reversible left ventricular (LV) dysfunction with characteristic stress or "Takotsubo" cardiomyopathy (SCM) after therapeutic pericardiocentesis in a patient with tubercular pericardial effusion. SCM following pericardiocentesis is uncommon, as opposed to the well-defined entity, pericardial decompression syndrome (PDS). PDS is defined as a paradoxical deterioration of hemodynamics and development of severe biventricular dysfunction, cardiogenic shock, and pulmonary edema after uneventful, often large volume pericardiocentesis in patients of pericardial effusion.

Real-world challenges in the management of acute myeloid leukemia: a single-center experience from North India.

BACKGROUND: The outcome of acute myeloid leukemia (AML) in low-middle-income countries (LMIC) is dismal due to delayed clinical presentation and infection-related complications. We aimed to analyze the outcome of patients with AML and the factors associated with its prognosis. METHODS: A retrospective observational study was conducted at a tertiary care university hospital in North India from January 2015 to December 2019. RESULTS: A total of 137 AML patients (median age 32 year (3-66 years) received intensive chemotherapy during study period. The median delay from diagnosis to treatment was 45 days (6-177 days). Among the 352 febrile neutropenia (FN) episodes analyzed, 175 (49.7%) were culture positive; Gram-negative multi-drug resistant organism (MDRO) sepsis during induction being 57.4% with 34.5% infections due to carbapenem-resistant Enterobacteriaceae (CRE) leading to a mortality rate of 14.6%. The median EFS and OS were 12.0 ± 1.57 (95% CI 8.91-15.08) and 15.0 ± 2.44 (95% CI 10.21-19.78) months respectively. Multivariable analysis revealed significant difference in median OS between favorable vs high risk AML groups (20.0 (95% CI: 12.50-27.49) vs 9.0 (95% CI: 2.99-15.01) months; p = 0.002); time from diagnosis to treatment (< 30 days vs ≥ 30 days; not reached vs 9.0 (95% CI: 6.81-11.18) months; p = 0.001), performance status (1 vs 2 vs 3; not reached vs 12.0 (95% CI: 10.32-13.67) vs 4.0 (95% CI:2.77-5.22); p = 0.001), and attainment of complete remission vs induction failure (not reached vs 6.0 (95% CI: 3.78-8.21); p = 0.002). CONCLUSION: Patient-related factors like delayed treatment initiation and high incidence of MDRO-associated sepsis are critical determinants of AML outcome in LMIC.