A novel indirect ELISA for diagnosis of dengue fever.

BACKGROUND & OBJECTIVES: Dengue fever (DF) is associated with significant morbidity and mortality in the tropical and sub-tropical regions of the world. Since there are no effective antiviral drugs for treatment, clinicians often rely on the accurate diagnosis of dengue fever to begin supportive therapy at early stages of the illness. The objective of this study was to develop an in-house dengue virus serotype 2 (DENV-2) non-structural protein- 5 (NS5) based indirect ELISA. METHODS: DENV-2 was raised in Vero cells and the viral proteins were separated and subsequently the NS5 protein was eluted. Serum samples from primary and secondary dengue fever patients; and acute and convalescent samples from Japanese encephalitis (JE) and West Nile virus (WNV) cases were used to validate the ELISA. RESULTS: The assay was found to be 100 per cent specific in detecting DENV-2 specific antibodies from patient's serum. However, in terms of sensitivity, the assay could detect IgM antibodies only from 90 per cent of the primary dengue samples. The IgM/IgG ratio of the primary and secondary samples was 7.24 and 0.64, respectively. INTERPRETATION & CONCLUSIONS: The results indicate that the DENV-2 NS5 ELISA is dengue group specific and can be used to differentiate dengue infection from other circulating Flavivirus infections. This NS5 ELISA can also be used to distinguish between primary and secondary dengue fever on the basis of IgM/IgG ratios. Further studies with larger sample sizes and different DENV serotypes are required to validate the ELISA.

Role of neoadjuvant peptide receptor radionuclide therapy in unresectable and metastatic gastro-entero-pancreatic neuroendocrine neoplasms: A scoping review.

Peptide receptor radionuclide therapy (PRRT) is an established therapy for metastatic neuroendocrine neoplasms (NEN). The role of PRRT as a neoadjuvant treatment prior to surgery or other local therapies is uncertain. This scoping review aimed to define the landscape of evidence available detailing the utility of PRRT in the neo-adjuvant setting, including the clinical contexts, efficacy, and levels of evidence. A comprehensive literature search of PUBMED, SCOPUS, and EMBASE through to December 2022 was performed to identify reports of PRRT use as neoadjuvant therapy prior to local therapies. Observational studies and clinical trials were included. A total of 369 records were identified by the initial search, and 17 were included in the final analysis, comprising 179 patients treated with neoadjuvant PRRT. Publications included case reports, retrospective cohort series and a phase 2 trial. Definitions of unresectable disease were variable. Radioisotopes used included 177Lu (n = 142) and 90Y (n = 36), used separately (n = 178) or in combination (n = 1). A combination of PRRT with chemotherapy was also explored (n = 2). Toxicity data was reported in 11/17 studies. Survival analysis was reported in 3/17 studies. Surgical resection following PRRT was reported for both the primary tumor (n = 71) and metastases (n = 12). Resection rates could not be calculated as not all publications reported whether resection was completed. Published literature exploring the use of PRRT in the neoadjuvant setting is mostly limited to case reports and retrospective cohort studies. From these limited data there is reported to be a role of PRRT in neoadjuvant setting in the literature. However, the low quality of evidence precludes any definite conclusion on the grade of disease, site of primary, isotope used or use of concomitant chemotherapy that can benefit from this application. Further prospective studies will require collaboration between multiple centers to gain sufficient high-quality evidence.

Pharmacological assessment of Ru(II) complex with GidA protein- A novel topoisomerase II inhibitor towards cancer therapeutics.

The interactions of ruthenium(II) complex with Glucose inhibited division protein A (GidA protein) was studied through various spectroscopic techniques with the ultimate goal of preparing adducts with good selectivity for cancer cells. In all the cases, formation of a tight metal-protein conjugate was observed. The influence of pH, reducing agents and chelators on the formation of adduct was analysed by UV- visible spectroscopy. While there was no effect on the addition of sodium ascorbate, some alterations on some selected bands were seen on the UV-visible spectra on the addition of EDTA. The adduct was stable in the pH range of 5-8. Addition of ruthenium(II) complex effectively quenched the intrinsic fluorescence of GidA and it occurred through static quenching. The effect of ruthenium(II) complex on the conformation of GidA has been examined by analyzing CD spectrum. Though, there was some conformational changes observed in the presence of ruthenium(II) complex, α- helix in the secondary structure of GidA retained its identity. Molecular docking of ruthenium(II) complex with GidA also indicated that GidA docks through hydrophobic interaction. The stable semisynthetic complex (ruthenium(II) complex with GidA) was checked for topoisomerase II inhibition. Relaxation and decatenation assay proved topoisomerase II inhibition of semisynthetic complex.Communicated by Ramaswamy H. Sarma.

Comparison of nitrate augmented Tc-99m tetrofosmin gated SPECT imaging with FDG PET imaging for the assessment of myocardial viability in patients with severe left ventricular dysfunction.

BACKGROUND: Of various nuclear medicine techniques, F-18/flourodeoxyglucose (FDG) positron emission tomography (PET) is considered as the best modality for the assessment of viable myocardium (VM). In this study, we compared the diagnostic accuracy of nitrate augmented Tc-99m tetrofosmin gated G-single-photon emission computed tomography (SPECT) with FDG PET. METHODS: 54 consecutive cases of angiographically proven CAD with severe LV dysfunction were enrolled in the study. The patients underwent Tc-99m tetrofosmin G-SPECT and FDG PET as per the standard protocols and were compared. RESULTS: SPECT data analysis indicated functional abnormalities in 661/918 myocardial segments. F-18 FDG PET revealed VM in 496/661 segments. The diagnostic accuracy of baseline NAC, postnitrate NAC, baseline AC, and postnitrate AC Tc-99m tetrofosmin SPECT was 84%, 87%, 90%, and 94%, respectively. κ values for NAC baseline, NAC postnitrate, AC baseline, and AC postnitrate Tc-99m tetrofosmin G-SPECT were 0.65, 0.70, 0.77, and 0.85, respectively. Attenuation correction revealed viability additionally in 46 segments which were non-viable on NAC postnitrate study (P < .001). Nitrate augmentation showed viability additionally in 25 segments which were non-viable on AC baseline scan (P = .004). On patient-based analysis FDG PET changes the management only in 13% (7/54) of patients. CONCLUSIONS: Nitrate augmented AC Tc-99m tetrofosmin G-SPECT shows excellent (κ = .85) agreement with FDG PET. FDG PET changes management only in 13% of the patients. Tc-99m tetrofosmin G-SPECT being more widely available and cheaper imaging modality can be reliably used to detect VM where FDG PET is not available.

Radiological Features of Zollinger-Ellison Syndrome: A Report of Two Cases.

Hypersecretion of gastrin from duodenal or pancreatic gastrinomas results in a rare clinical entity called Zollinger-Ellison syndrome (ZES). It mostly presents with abdominal pain and diarrhea. ZES may be sporadic or occur in association with multiple endocrine neoplasia type 1. Usually, ZES manifests between 20 and 50 years. We report two cases of patients who presented with abdominal pain, vomiting, watery diarrhea, and significant weight loss.

Role of Imaging in a Case of Toxoplasmosis Presenting as Generalized Lymphadenopathy.

Toxoplasmosis is caused by Toxoplasma gondii an obligate protozoan intracellular parasite. The disease has variable prevalence globally and is usually asymptomatic. Pregnant and immunocompromised people are at risk of getting infected. Enlarged lymph nodes are the most frequently observed clinical form of Toxoplasma in humans, mostly affecting posterior cervical nodes. Other organs usually affected are the brain and eyes. We present a case of toxoplasmosis with generalized lymphadenopathy mimicking metastasis in a lady with a previous history of operated pancreatic neoplasm.

Comparison of LVEF assessed by 2D echocardiography, gated blood pool SPECT, 99mTc tetrofosmin gated SPECT, and 18F-FDG gated PET with ERNV in patients with CAD and severe LV dysfunction.

INTRODUCTION: Left ventricular ejection fraction (LVEF) is the single most important predictor of prognosis in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. Equilibrium radionuclide ventriculography (ERNV) is considered the most reliable technique for assessing LVEF. Most of these patients undergo two dimensional (2D) echocardiography and myocardial viability study using gated myocardial perfusion imaging (MPI) or gated F-fluorodeoxyglucose (F-FDG) PET. However, the accuracy of LVEF assessed by these methods is not clear. This study has been designed to assess the correlation and agreement between the LVEF measured by 2D echocardiography, gated blood pool single photon emission computed tomography (SPECT), Tc tetrofosmin gated SPECT, and F-FDG gated PET with ERNV in CAD patients with severe LV dysfunction. PATIENTS AND METHODS: Patients with CAD and severe LV dysfunction [ejection fraction (EF) <35 assessed by 2D echocardiography] were prospectively included in the study. These patients underwent ERNV along with gated blood pool SPECT, Tc tetrofosmin gated SPECT, and F-FDG gated PET as per the standard protocol for myocardial viability assessment and LVEF calculation. Spearman's coefficient of correlation (r) was calculated for the different sets of values with significance level kept at a P-value less than 0.05. Bland-Altman plots were inspected to visually assess the between-agreement measurements from different methods. RESULTS: Forty-one patients were prospectively included. LVEF calculated by various radionuclide methods showed good correlation with ERNV as follows: gated blood pool SPECT, r=0.92; MPI gated SPECT, r=0.85; and F-FDG gated PET, r=0.76. However, the correlation between 2D echocardiography and ERNV was poor (r=0.520). The Bland-Altman plot for LVEF measured by all radionuclide methods showed good agreement with ERNV. However, agreement between 2D echocardiography and ERNV is poor, as most of the values in this plot gave a negative difference for low EF and a positive difference for high EF. The mean difference between various techniques [2D echocardiography (a), gated blood pool SPECT (b), MPI gated SPECT (c), F-FDG gated PET (d)] and ERNV (e) was as follows: (a)-(e), 3.3; (b)-(e), 5; (c)-(e), 1.1; and (d)-(e), 2.9. The best possible correlation and agreement was found between MPI gated SPECT and ERNV. CONCLUSION: This study showed good correlation and agreement between MPI gated SPECT and F-FDG gated PET with ERNV for LVEF calculation in CAD patients with severe LV dysfunction. Thus, subjecting patients who undergo viability assessment by MPI gated SPECT or F-FDG gated PET to a separate procedure like ERNV for LVEF assessment may not be warranted. As the gated blood pool SPECT also showed good correlation and agreement with ERNV for LVEF assessment in CAD patients with severe LV dysfunction, with better characteristics than ERNV, it can be routinely used whenever accurate LVEF assessment is needed.

Comparison of various criteria in interpreting end of therapy F-18 labeled fluorodeoxyglucose positron emission tomography/computed tomography in patients with aggressive non-Hodgkin lymphoma.

Various interpretation criteria exist to assess end of therapy F-18 labeled fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in lymphoma. This study was carried out to compare these criteria. Data of 69 patients with aggressive non-Hodgkin lymphoma (AGR-NHL) who underwent FDG PET/CT at the end of therapy and were followed up for a minimum period of 1 year (median follow-up period 17 months) were evaluated. Twenty-eight of the 69 patients were found to have residual/recurrent disease during follow-up. The accuracy for predicting residual disease of International Harmonization Project (IHP) criteria, London criteria and Gallamini criteria was 71.0%, 84.0% and 88.4%, respectively. Gallamini and London criteria had greater accuracies in predicting residual disease than IHP criteria (p = 0.0001). The major difference in accuracy was due to the low positive predictive value of IHP criteria. Positive predictive values (PPVs) of both London and Gallamini criteria (79.3% and 88.5%, respectively) were high when compared with that of IHP criteria (60.5%) (p = 0.001). Negative predictive values (NPVs) were similar for all the criteria. In conclusion, Gallamini and London criteria had higher accuracy when interpreting end of therapy FDG PET/CT studies in AGR-NHL. London criteria can be used preferentially over Gallamini criteria because of simplicity in interpretation and reproducibility.

A novel indirect ELISA for diagnosis of dengue fever.

Background & objectives: Dengue fever (DF) is associated with significant morbidity and mortality in the tropical and sub-tropical regions of the world. Since there are no effective antiviral drugs for treatment, clinicians often rely on the accurate diagnosis of dengue fever to begin supportive therapy at early stages of the illness. The objective of this study was to develop an in-house dengue virus serotype 2 (DENV-2) non-structural protein- 5 (NS5) based indirect ELISA. Methods: DENV-2 was raised in Vero cells and the viral proteins were separated and subsequently the NS5 protein was eluted. Serum samples from primary and secondary dengue fever patients; and acute and convalescent samples from Japanese encephalitis (JE) and West Nile virus (WNV) cases were used to validate the ELISA. Results: The assay was found to be 100 per cent specific in detecting DENV-2 specific antibodies from patient’s serum. However, in terms of sensitivity, the assay could detect IgM antibodies only from 90 per cent of the primary dengue samples. The IgM/IgG ratio of the primary and secondary samples was 7.24 and 0.64, respectively. Interpretation & conclusions: The results indicate that the DENV-2 NS5 ELISA is dengue group specific and can be used to differentiate dengue infection from other circulating Flavivirus infections. This NS5 ELISA can also be used to distinguish between primary and secondary dengue fever on the basis of IgM/IgG ratios. Further studies with larger sample sizes and different DENV serotypes are required to validate the ELISA.