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BACKGROUND: The presence of skeletal metastases significantly influences the therapeutic strategy adopted for soft tissue sarcoma. However, literature on the prevalence of skeletal metastases in soft tissue sarcoma is limited and none of the available data is based on the Indian patient population. AIM: To determine the prevalence of skeletal metastases at presentation in patients of soft tissue sarcoma and to rationalise the use of preoperative skeletal scintigraphy in such patients. METHODS AND MATERIAL: Preoperative bone scans were evaluated in 122 patients with soft tissue sarcoma (median age, 34 years; range, 4-83). The scans were classified into 3 grades: Grade 1: metastases very likely; Grade 2: equivocal; Grade 3: normal or benign lesion. In all the patients studied, the ability of the patient to localize the site or sites of pain was recorded and that was correlated with the site of metastases in scintigraphy. RESULT: Seventeen (13.9%) patients had Grade 1 scan; 16 of them had bony pain that was not readily explainable by trauma or other local factors. Ten ( 8.1%) patients had Grade 2 scan, five of them had bony pain which was not readily explainable by trauma or other local factors. Ninety-five patients (77.8%) had Grade 3 scan. Of these, 9 had localised bone pain which could be definitely associated with trauma or joint degeneration. CONCLUSION: The prevalence of skeletal metastases at presentation in patients with soft tissue sarcoma is low (13.9%). The low rates of skeletal metastases in bone pain-free patients (0.9%) versus the high rate in symptomatic patients (76.1%) supports the use of bone scanning in symptomatic patients only. [ABSTRACT FROM AUTHOR]

A diverse set of 4,7-dihydro-[1,2,3]thiadiazolo[5,4-b]pyridine-6-carboxamides 4(a-o) was synthesized via a one-pot reaction of 5-amino-[1,2,3]thiadiazole, various aromatic aldehydes, and different acetoacetanilides, using glacial acetic acid. The resulting compounds were obtained in moderate to good yields. All the newly synthesized compounds were evaluated for their antimicrobial activity. Among them, compound 4 e demonstrated superior efficacy against the Salinivibrio proteolyticus strain of Gram-negative bacteria compared to ciprofloxacin. Compound 4 d exhibited the highest potency against the fungal strain Candida albicans, surpassing amphotericin B. The physicochemical characteristics of 4 d and 4 e were assessed. According to docking analysis, DHTDAPy 4 e shows a higher binding affinity of -7.2 kcal/mol in the binding cavity of the receptor. These findings illustrate the safety, tolerability, and potency of the newly synthesized DHTDAPy compounds against fungal and bacterial infections., (© 2024 Wiley-VCH GmbH.)

We report a case of pulmonary hypertension in association with right heart thrombus and mediastinal lymphadenopathy leading to the diagnostic dilemma of chronic thromboembolic pulmonary hypertension vs fibrosing mediastinitis despite of extensive noninvasive workup, considering different treatment strategies and therapeutic implications. Surgical findings provided a conclusive diagnosis and excellent prognosis., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

There is a continuous and pressing need to establish new brain-penetrant bioactive compounds with anti-cancer properties. To this end, a new series of 4'-((4-substituted-4,5-dihydro-1H-1,2,3-triazol-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile (OTBN-1,2,3-triazole) derivatives were synthesized by click chemistry. The series of bioactive compounds were designed and synthesized from diverse alkynes and N 3 -OTBN, using copper (II) acetate monohydrate in aqueous dimethylformamide at room temperature. Besides being highly cost-effective and significantly reducing synthesis, the reaction yielded 91-98 % of the target products without the need of any additional steps or chromatographic techniques. Two analogues exhibit promising anti-cancer biological activities. Analogue 4l shows highly specific cytostatic activity against lung cancer cells, while analogue 4k exhibits pan-cancer anti-growth activity. A kinase screen suggests compound 4k has single-digit micromolar activity against kinase STK33. High STK33 RNA expression correlates strongly with poorer patient outcomes in both adult and pediatric glioma. Compound 4k potently inhibits cell proliferation, invasion, and 3D neurosphere formation in primary patient-derived glioma cell lines. The observed anti-cancer activity is enhanced in combination with specific clinically relevant small molecule inhibitors. Herein we establish a novel biochemical kinase inhibitory function for click-chemistry-derived OTBN-1,2,3-triazole analogues and further report their anti-cancer activity in vitro for the first time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In this communication, we explored the synthesis of novel alkoxy-functionalised dihydropyrimido[4,5- b ]quinolinones using a microwave-assisted multicomponent reaction. All the synthesized molecules were screened for anti-proliferative and anti-invasive activity against glioblastoma cells. 5c shows the most potent anti-proliferative activity with a half maximal effective concentration of less than 3 μM against primary patient-derived glioblastoma cells. 5c effectively inhibited invasion and tumor growth of 3D primary glioma cultures in a basement membrane matrix. This suggests that the novel compounds could inhibit both the proliferation and invasive spread of glioma and they were selected for further study.

Owing to the massive importance of dihydropyrimidine (DHPMs) scaffolds in the pharmaceutical industry and other areas, we developed an effective and sustainable one-pot reaction protocol for the synthesis of ( R / S )-2-thioxo-DHPM-5-carboxanilides via the Biginelli-type cyclo-condensation reaction of aryl aldehydes, thiourea and various acetoacetanilide derivatives in ethanol at 100 °C. In this protocol, taurine was used as a green and reusable bio-organic catalyst. Twenty-three novel derivatives of ( R / S )-TDHPM-5-carboxanilides and their structures were confirmed by various spectroscopy techniques. The aforementioned compounds were synthesized via the formation of one asymmetric centre, one new C-C bond, and two new C-N bonds in the final product. All the newly synthesized compounds were obtained in their racemic form with up to 99% yield. In addition, the separation of the racemic mixture of all the newly synthesized compounds was carried out by chiral HPLC (Prep LC), which provided up to 99.99% purity. The absolute configuration of all the enantiomerically pure isomers was determined using a circular dichroism study and validated by a computational approach. With up to 99% yield of 4d, this one-pot synthetic approach can also be useful for large-scale industrial production. One of the separated isomers (4 R )-(+)-4 S developed as a single crystal, and it was found that this crystal structure was orthorhombic., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Somatostatin receptor (SSTR) imaging is a useful method in the diagnosis of acute myocarditis. We present a case of a 54-year-old male with a clinical diagnosis of acute myocarditis in whom, 68Ga-DOTANOC positron emission tomography/computed tomography PET/CT showed diffuse left ventricular myocardial uptake. SSTR imaging can act as a surrogate marker of active inflammation. SSTR imaging is useful in deciding site of biopsy, assessing response to therapy and for prognostication., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Nuclear Medicine.)

Neonatal herpes simplex virus (nHSV) infections often result in significant mortality and neurological morbidity despite antiviral drug therapy. Maternally transferred herpes simplex virus (HSV)-specific antibodies reduce the risk of clinically overt nHSV, but this observation has not been translationally applied. Using a neonatal mouse model, we tested the hypothesis that passive transfer of HSV-specific human mAbs can prevent mortality and morbidity associated with nHSV. The mAbs were expressed in vivo via vectored immunoprophylaxis or recombinantly. Through these maternally derived routes or through direct administration to pups, diverse mAbs to HSV glycoprotein D protected against neonatal HSV-1 and HSV-2 infection. Using in vivo bioluminescent imaging, both pre- and post-exposure mAb treatment significantly reduced viral load in mouse pups. Together these studies support the notion that HSV-specific mAb-based therapies could prevent or improve HSV infection outcomes in neonates., (© 2022 Backes et al.)

The availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing of vaccination in pregnancy impact maternal and neonatal immunity. Here, we characterize the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals and evaluate transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads. These analyses reveal lower vaccine-induced functions and Fc receptor-binding after Ad26.COV2.S compared to mRNA vaccination and subtle advantages in titer and function with mRNA-1273 versus BN162b2. mRNA vaccines have higher titers and functions against SARS-CoV-2 variants of concern. First and third trimester vaccination results in enhanced maternal antibody-dependent NK-cell activation, cellular and neutrophil phagocytosis, and complement deposition relative to second trimester. Higher transplacental transfer ratios following first and second trimester vaccination may reflect placental compensation for waning maternal titers. These results provide novel insight into the impact of platform and trimester of vaccination on maternal humoral immune response and transplacental antibody transfer., (© 2022. The Author(s).)

The severe acute respiratory syndrome coronavirus 2 pandemic has resulted in the development of various therapeutics to treat and prevent major complications related to the virus; pregnant patients are vulnerable to acquiring severe acute respiratory syndrome coronavirus 2 because of frequent contact with the healthcare setting. Despite the publication of a plethora of case series and randomized control trials of severe acute respiratory syndrome coronavirus 2 therapeutics, few have addressed treatment in the pregnant population. To date, there has been no published review of therapeutic options in the treatment of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection. Here, we provide a review of available treatments for severe acute respiratory syndrome coronavirus 2, various trials with inclusion and exclusion of the pregnant patients, and potential side effects of each treatment in the pregnant patient., (© 2020 Elsevier Inc. All rights reserved.)

Herpes simplex virus (HSV) can cause severe infection in neonates leading to mortality and lifelong morbidity. Prophylactic approaches, such as maternal immunization, could prevent neonatal HSV (nHSV) infection by providing protective immunity and preventing perinatal transmission. We previously showed that maternal immunization with a replication-defective HSV vaccine candidate, dl 5-29, leads to transfer of virus-specific antibodies into the neonatal circulation and protects against nHSV neurological sequela and mortality (C. D. Patel, I. M. Backes, S. A. Taylor, Y. Jiang, et al., Sci Transl Med, 11:eaau6039, 2019, https://doi.org/10.1126/scitranslmed.aau6039). In this study, we evaluated the efficacy of maternal immunization with an experimental trivalent (gC2, gD2, and gE2) subunit vaccine to protect against nHSV. Using a murine model of nHSV, we demonstrated that maternal immunization with the trivalent vaccine protected offspring against nHSV-disseminated disease and mortality. In addition, offspring of immunized dams were substantially protected from behavioral pathology following HSV infection. This study supports the idea that maternal immunization is a viable strategy for the prevention of neonatal infections. IMPORTANCE Herpes simplex virus is among the most serious infections of newborns. Current antiviral therapies can prevent mortality if infection is recognized early and treated promptly. Most children who survive nHSV develop lifelong neurological and behavioral deficits, despite aggressive antiviral treatment. We propose that maternal immunization could provide protection against HSV for both mother and baby. To this end, we used a trivalent glycoprotein vaccine candidate to demonstrate that offspring are protected from nHSV following maternal immunization. Significantly, this approach protected offspring from long-term behavioral morbidity. Our results emphasize the importance of providing protective immunity to neonates during this window of vulnerability., (Copyright © 2020 American Society for Microbiology.)

Purpose of the Study: Well-differentiated thyroid carcinomas have good prognosis, but as it de-differentiates, the survival rates go down. Early identification of such patients needs a marker which indicates the dedifferentiation process. CYFRA 21.1 has also shown to be increased in patients with 131 I refractory thyroid cancer. We tested whether CYFRA 21.1 can differentiate between 131 I avid and refractory tumors., Methodology: Well-differentiated thyroid cancer patients with known distant metastases were accrued and tested for stimulated and unstimulated thyroglobulin and CYFRA 21.1. All patients underwent 131 I whole-body scan, 131 I post therapy scan, and 18 F-Fluorodeoxyglucose positron emission tomography-computed tomography. Those with even a single 131 I nonavid lesion were considered 131 I refractory disease. CYFRA 21.1 of both 131 I avid and nonavid was compared, and CYFRA 21.1 levels against disease extent were analyzed., Results: CYFRA 21.1 levels were significantly elevated in 131 I refractory group. A cutoff value of 2.07 ng/ml distinguished between 131 I avid and refractory disease with high sensitivity and specificity (88% and 89. 7%, respectively). However, CYFRA 21.1 levels were similar in patients when analyzed based on disease sites., Conclusion: CYFRA 21.1 can be utilized to differentiate between 131 I avid and refractory diseases. Further long-term studies are required to use it as a predictive and prognostic marker., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Nuclear Medicine.)

3D printing enables on-demand solutions for a wide spectrum of needs ranging from personal protection equipment to medical devices and isolation wards. This versatile technology is suited to address supply-demand imbalances caused by socio-economic trends and disruptions in supply chains., Competing Interests: Competing interestsThe authors declare no competing interests., (© Springer Nature Limited 2020.)

Dandruff is one of the most common clinically manifested and studied scalp disorders. It has been associated with both bacteria and fungi. Bacteria and fungi inhabiting the scalp are known to influence each other and manifestation of dandruff. Fungal and bacterial isolates from scalp epithelial flakes (dandruff) were identified by rDNA sequencing. Local oils were tested for fungal and bacterial inhibition, interaction and biofilm formation, cell-cell interactions were studied by auto aggregation and surface thermodynamics studies. The isolates Bacillus sp.C2b1 (MK036745) and Malassezia sp. C2y1 (MK036746) were inhibited by Mahabhrungraj oil. The fungal morphological switch was evident and dependent on nutrition. Cell aggregation studies suggested the interaction of bacteria with yeast (non-pathogenic) phase of the fungus. Bacterial and yeast cells were found to be compatible for biofilm formation. The fungal mycelial surfaces were found to be conducive for interaction with both bacterial cells and yeast forms. The results here indicate the significance of mycelial phase of scalp-isolated fungus in interaction with the bacterial surfaces and also with self-yeast phase surface. This is the first report of the interaction between scalp-isolated microorganisms with respect to their surface interaction capabilities., Competing Interests: Conflict of interestThe authors declare no conflict of interest in publishing this manuscript.

Neonatal herpes simplex virus (nHSV) infections cause devastating morbidity and mortality in infants. Most nHSV cases are associated with primary maternal infection, consistent with the hypothesis that maternal immunity is protective. In humans, we found HSV-specific neutralizing antibodies in newborns of immune mothers, indicating that placentally transferred HSV-specific antibody is protective. Using a murine model, we showed that passive administration of HSV-specific antibody to dams prevented disseminated infection and mortality in pups. Maternal immunization with an HSV-2 replication-defective vaccine candidate, dl 5-29, led to transfer of HSV-specific antibodies into neonatal circulation that protected against nHSV neurological disease and death. Furthermore, we observed considerable anxiety-like behavior in adult mice that had been infected with low doses of HSV as neonates, despite a notable lack of signs of infection. This phenotype suggests that nHSV infection can have an unsuspected and permanent impact on behavior. These behavioral sequelae of nHSV were prevented by maternal immunization with dl 5-29, demonstrating an unexpected benefit of immunization. These findings also support the general concept that maternal immunization can prevent neurotropic neonatal infections and associated morbidity and mortality., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Coronary artery disease (CAD) is the leading cause of death in patients with type 2 diabetes mellitus (T2DM) and may be asymptomatic., Objective: The objective of this study was to assess the prevalence of asymptomatic myocardial ischemia in patients with T2DM using stress myocardial perfusion imaging., Methods: We evaluated 97 consecutive patients with T2DM without clinical evidence of CAD presenting to Cardiology and Endocrinology clinics using Tc-99m MIBI gated single-photon emission-computed tomography (SPECT) myocardial perfusion imaging for the presence of asymptomatic CAD., Results: Abnormal myocardial perfusion was observed in 10 patients (10.3%). Of these, one half of patients had reversible myocardial perfusion defects suggestive of inducible myocardial ischemia. The other half had fixed perfusion defects suggestive of previous silent myocardial infarctions. Small and moderate reversible perfusion defects were observed in 3 and 2 patients, respectively. The fixed perfusion defects observed in 5 patients were medium sized. The presence of asymptomatic ischemia was significantly associated with age and smoking but not with other traditional cardiac risk factors., Conclusion: Ten percent of patients with T2DM with no clinical evidence of CAD were found to have evidence of asymptomatic ischemia or infarction., (Copyright © 2018 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: Manual thrombus aspiration during primary percutaneous intervention provides us with aspirated thrombus sample, that may contain material from the disrupted plaque. Immunohistopathological analysis of thrombus can yield valuable information about the clinical and cardiovascular outcomes and possible mechanisms of myocardial infarction., Material and Methods: We studied and analysed the immunohistopathological features of coronary thrombus aspirated from patients undergoing primary percutaneous coronary angioplasty. Immunohistological staining included markers namely CD68, SMA and CD34 for macrophages, smooth muscle actin and endothelium, respectively. Major adverse cardiac events, angiographic outcome and infarct size were also noted., Results: Fifty-three patients (Mean age - 51.3±13years; males-47) who underwent primary percutaneous coronary intervention with aspiration thrombectomy were enrolled. Thrombus was successfully aspirated in 40 of 53 patients (75.4%). Patients with successful thrombus aspiration had higher ST-segment resolution (≥50%) as compared to patients with failed thrombus aspiration. Presence of RBC-rich thrombus on microscopy was more commonly associated with post-procedure TIMI flow of <2 as compared to patients with fibrin-rich thrombus and a trend towards lower myocardial blush grade<2 (P=0.10), and a significantly higher final infarct size (37.5±5% vs 25±15%; P=0.04 of myocardium) on nuclear scan. Immunohistology revealed presence of plaque material in 72% (26/36) of the samples., Conclusions: Immunohistopathological evaluation of intracoronary thrombus may be of prognostic importance. High prevalence of plaque material in the aspirated intracoronary thrombus suggests plaque rupture as a possible etiology for vessel occlusion in these patients., Short Summary: Immunohistopathological evaluation of intracoronary thrombus reveals high prevalence of plaque material in the aspirated intracoronary thrombus suggesting plaque rupture as a possible etiology for vessel occlusion in Indian STEMI patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to prospectively evaluate the role of various quantitative and semiquantitative metabolic parameters derived from dynamic and static baseline F-FDG PET/CT in prediction of overall survival (OS) in non-small cell lung cancer (NSCLC) patients who were planned to undergo platinum-based chemotherapy., Methods: Sixty patients (51 male and 9 female patients) with biopsy-proven NSCLC and mean age 59.55 ± 10.06 years who were planned to undergo platinum-based chemotherapy were enrolled in the study. Each patient underwent a baseline regional dynamic and a static whole-body F-FDG PET/CT after injecting 0.21 mCi/kg (5.18-7.77 MBq/kg) of F-FDG intravenously. Two dynamic PET/CT parameters, that is, net influx rate constant and glucose metabolic rate at 30 and 60 minutes, were evaluated. In addition, whole-body PET/CT parameters, that is, SUVmax, average SUV, tumor-to-background ratio, metabolic tumor volume (MTV), total lesion glycolysis (TLG) of the primary tumor, and MTV and TLG of whole-body tumor lesions, were evaluated. Best possible cutoffs for all parameters were calculated using receiver operating characteristic curve analysis. Survival analysis was performed using log-rank test, Kaplan-Meier curves, and Cox proportional hazards model to determine the prognostic markers for OS., Results: The median follow-up period was 4.4 months (range, 8 days to 15.9 months). In univariate analysis, the 4 static whole-body PET/CT parameters, that is, MTV, TLG, and MTV and TLG of whole-body tumor lesions, were found to be significantly associated with OS with cutoff values of 120, 800, 160, and 1350 cm and hazard ratios of 3.64 (P = 0.001), 3.35 (P = 0.002), 2.51 (P = 0.019), and 2.69 (P = 0.008), respectively. In multivariate survival analysis, MTV was found to be an independent prognostic marker for OS., Conclusions: Baseline MTV and TLG evaluated from primary tumor as well as the whole-body tumor lesions are reliable prognostic markers of OS in NSCLC patients undergoing platinum-based chemotherapy. However, other baseline whole-body PET/CT parameters (SUVmax, average SUV, and tumor-to-background ratio) and dynamic PET/CT parameters (net influx rate constant, glucose metabolic rate) have no prognostic value in these patients.

While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization. IMPORTANCE Herpes simplex virus 1 is a common infection of the nervous system that causes devastating neonatal disease. Using mouse and human tissue, we discovered that antiviral antibodies accumulate in neural tissue after HSV-1 infection in adults. Similarly, these antibodies pass to the offspring during pregnancy. We found that antiviral maternal antibodies can readily access neural tissue of the fetus and neonate. These maternal antibodies then protect neonatal mice against HSV-1 neurological infection and death. These results underscore the previously unappreciated role of maternal antibodies in protecting fetal and newborn nervous systems against infection. These data suggest that maternal immunization would be efficacious at preventing fetal/neonatal neurological infections., (Copyright © 2017 Jiang et al.)

Troponin elevation is required to diagnose acute myocardial infarction (AMI), yet elevated values are often encountered in noncardiac disease states. We evaluated inpatient (IP) and outpatient (OP) encounters at 14 hospitals in calendar year 2014 and found that troponin assays were performed during 12% of all OP visits and 29% of all IP visits: 82,853 encounters in all. We employed an expert panel to estimate the likelihood of AMI based on primary International Statistical Classification of Diseases and Related Health Problems, 9th edition diagnoses. We compared IP and OP testing, finding that AMI would not be expected in most IP encounters. Sepsis was the most common diagnosis associated with IP troponin testing. We found an association between troponin testing in patients with sepsis and utilization of electrocardiography, echocardiography, and cardiac catheterization. Our data indicate that troponin testing has expanded beyond patient populations in whom AMI might be expected., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Although thymoma is a rare tumor, it is the most common anterior mediastinal tumor, usually affecting the adults in their fifth and sixth decade. We present a case of 68-year-old man with history of myocardial infarction, who presented to the cardiology OPD with recent onset of exertional dyspnea. On 99mTc MIBI myocardial perfusion SPECT, there was an extra cardiac accumulation of radiotracer in the anterior mediastinum just above the heart, which later was diagnosed as thymoma on histopathology., Competing Interests: There are no conflicts of interest.

Objective: The effect of cardiac resynchronization therapy (CRT) on right ventricular ejection fraction (RVEF) and intraright ventricular dyssynchrony (IRVD) is questionable. Furthermore, it is unclear whether baseline IRVD and RVEF influences response to CRT. The aim of this study is to evaluate the effects of CRT on RVEF and IRVD and to investigate whether baseline IRVD and RVEF impacts response to CRT., Patients and Methods: Equilibrium radionuclide angiography and clinical evaluation were performed in 32 nonischemic dilated cardiomyopathy patients before and 3 months after CRT implantation. SD of the right ventricle mean phase angle expressed in degrees was used to quantify right intraventricular synchrony. RVEF was also evaluated., Results: There was no significant change in the RVEF and IRVD between the baseline and at 3 months after CRT equilibrium radionuclide angiography studies (RVEF: 40.5±10.6 vs. 40.4±10.4%, P=0.75; IRVD: 36.6±13.7 vs. 36.3±13.3°, P=0.35). Of 32 patients, 6/14 (43%) patients with baseline IRVD responded compared with 16/18 (89%) without baseline IRVD (P=0.02)., Conclusion: CRT did not cause any significant change in RVEF and IRVD. Patients with IRVD are less likely to respond to CRT.

Aims: The aim of this study was to evaluate equilibrium radionuclide angiography (ERNA) in prediction of response to cardiac resynchronization therapy (CRT) in non-ischaemic dilated cardiomyopathy (DCM) patients., Methods and Results: Thirty-two patients (23 males, 57.5 ± 12.1 years) were prospectively included. Equilibrium radionuclide angiography and clinical evaluation were performed before and 3 months after CRT implantation. Standard deviation of left ventricle mean phase angle (SD LVmPA) and difference between LV and right ventricle mPA (LV-RVmPA) expressed in degrees (°) were used to quantify left intraventricular synchrony and interventricular synchrony, respectively. Left ventricular ejection fraction (LVEF) was also evaluated. At the baseline, mean NYHA class was 3.3 ± 0.5, LVEF 22.5 ± 5.6%, mean QRS duration 150.3 ± 18.2 ms, SD LVmPA 43.5 ± 18°, and LV-RVmPA 30.4 ± 15.6°. At 3-month follow-up, 22 patients responded to CRT with improvement in NYHA class ≥1 and EF >5%. Responders had significantly larger SD LVmPA (51.2 ± 13.9 vs. 26.5 ± 14°) and LV-RVmPA (35.8 ± 13.7 vs. 18.4 ± 13°) than non-responders. Receiver-operating characteristic curve analysis demonstrated 95% sensitivity and 80% specificity at a cut-off value of 30° for SD LVmPA, and 81% sensitivity and 80% specificity at a cut-off value of 23° for LV-RVmPA in prediction of response to CRT., Conclusion: Baseline SD LVmPA and LV-RVmPA derived from ERNA are useful for prediction of response to CRT in non-ischaemic DCM patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Objective: The aim of the study was to compare the myocardial perfusion defects in patients with right ventricular outflow tract (RVOT) and right ventricular apex (RVA) pacing on stress-rest Tc-tetrofosmin myocardial perfusion single-photon emission computed tomography., Patients and Methods: A total of 31 patients with permanent pacemakers (RVOT: 16 and RVA: 15) underwent stress-rest Tc-tetrofosmin involving a 1-day protocol. All patients underwent 1-day low-dose stress-gated and high-dose rest-gated Tc-tetrofosmin myocardial perfusion single-photon emission computed tomography imaging., Results: Fixed perfusion defects were noted in 13 (42%) of 31 patients. Two (13%) patients of the RVOT group and 11 (69%) patients of the RVA group showed fixed perfusion defects (P=0.003). The fixed perfusion defects were located in the anteroapical, anteroseptal, and apical in the RVOT pacing group and in the apical, distal anteroseptal, inferoapical, distal anterior, and distal inferoseptal in the RVA pacing group. On univariate analysis, the incidence of perfusion defects was significantly associated with apical pacing, longer pQRS duration, and higher percentage of ventricular pacing. On multivariate analysis, the site of pacemaker insertion was found to be the most important pacemaker parameter determining the incidence of perfusion defects. Importantly, the duration of postpacemaker implantation did not show any significant relation to the incidence of perfusion defects., Conclusion: Fixed perfusion abnormalities are observed in patients with pacemakers and are independent of duration of time since implantation. RVOT pacing is associated with fewer incidences of myocardial perfusion abnormalities compared with RVA pacing.

Background: Chronic ventricular pacing is known to adversely affect left ventricular (LV) function. Studies comparing right ventricular outflow tract (RVOT) pacing with RV apical (RVA) pacing have shown heterogeneous outcomes. Our aim was to objectively assess LV function and mechanical dyssynchrony in patients with RVOT and RVA pacing using equilibrium radionuclide angiography (ERNA)., Methods: Fifty-one patients who underwent permanent pacemaker implantation and had normal LV function were prospectively included. Twenty-nine patients had pacemaker lead implanted in the RVOT and 22 at the RVA site. All patients underwent ERNA within 5 days post-pacemaker implantation and follow-up studies at 6 and 12 months. Standard deviation of LV mean phase angle (SD LV mPA) expressed in degrees, which was derived by Fourier first harmonic analysis of phase images, was used to quantify left intraventricular dyssynchrony., Results: No significant difference was observed between the two groups with respect to indication (P = .894), Type/mode (P = .985), and percentage of ventricular pacing (P = .352). Paced QRS duration was significantly longer in RVA group than RVOT group (P = .05). There was no statistically significant difference between the RVA and RVOT groups at baseline with respect to LVEF (P = .596) and SD LV mPA (P = .327). Within the RVA group, a significant decline in LVEF was observed over 12-month follow-up (from 57.3% ± 5.32% to 55.6% ± 6.25%; P = .012). In the RVOT group, the change in LVEF was not statistically significant (from 56.7% ± 4.08% to 54.3% ± 6.63%; P = .159). No significant change in SD LV mPA was observed over 12-month follow-up within the RVA group (from 10.5 ± 2.58° to 10.4 ± 3.54°; P = 1.000) as well as in the RVOT group (from 9.7 ± 3.28° to 9.4 ± 2.85°; P = .769). However, between the RVA and RVOT groups, no significant difference was observed at 12-month follow-up in terms of LVEF and dyssynchrony (LVEF P = .488; SD LV mPA P = .296)., Conclusion: No significant difference was observed between RVOT and RVA groups with regard to LV function and synchrony over a 12-month follow-up. RVOT pacing offers may lead to better preservation of LV function on longer follow-up.

Background & Objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy., Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI)., Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study., Interpretation & Conclusions: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Permanent pacing, being non physiological, often results in ventricular dysfunction over time. Narrower paced QRS duration from pacing the right ventricular outflow tract septum, might result in relatively preserved ventricular function over long term follow up.

Objective: The aim of the study was to evaluate gated myocardial perfusion SPECT (GMPS) in the prediction of response to cardiac resynchronization therapy (CRT) in nonischaemic dilated cardiomyopathy patients., Patients and Methods: Thirty-two patients (23 men, mean age 57.5±12.1 years) with severe heart failure, who were selected for CRT implantation, were prospectively included in this study. Patients with coronary heart disease and structural heart diseases were excluded. ⁹⁹mTc-MIBI GMPS and clinical evaluation were performed at baseline and 3 months after CRT implantation. In GMPS, first-harmonic fast Fourier transform was used to extract a phase array using commercially available software. Phase standard deviation (PSD) and phase histogram bandwidth (PHB) were used to quantify cardiac mechanical dyssynchrony (CMD). Left ventricular ejection fraction was evaluated., Results: At baseline evaluation the mean NYHA class was 3.3±0.5, left ventricular ejection fraction was 23.2±5.3% and mean QRS duration was 150.3±18.2 ms. PSD was 55.8±19.2° and PHB was 182.1±75.8°. At 3-month follow-up, 22 patients responded to CRT with improvement in NYHA class by more than 1 grade and in ejection fraction by more than 5%. Responders had significantly larger PSD (63.6±16.6 vs. 38.7±12.7°) and PHB (214.8±63.9 vs. 110.2±43.5°) compared with nonresponders. Receiver-operating characteristic curve analysis demonstrated 86% sensitivity and 80% specificity at a cutoff value of 43° for PSD and 86% sensitivity and 80% specificity at a cutoff value of 128° for PHB in the prediction of response to CRT., Conclusion: Baseline PSD and PHB derived from GMPS are useful for prediction of response to CRT in nonischaemic dilated cardiomyopathy patients.

Background: The relationship between perfusion pattern and stress-induced changes in left ventricular mechanical dyssynchrony (LVMD) on stress-rest thallium-201-gated SPECT myocardial perfusion imaging (Tl-201 SPECT MPI) is not clear. The aim of the study is to assess the relation of perfusion pattern with stress-induced changes in LVMD on Tl-201 MPI., Methods: Data of 194 patients who underwent exercise-rest Tl-201 MPI between January to December 2012 at our institute was retrospectively evaluated. Institute Ethical committee approval was obtained. Fifty patients who underwent Tl-201 MPI for suspected CAD and had normal LV perfusion and function on MPI were taken as normal group. Patients with perfusion abnormalities (n = 144) were divided into three groups: ischemia (n = 66), infarct (n = 32), and mixed group (n = 46; ischemia and infarct both). Summed stress score, summed rest score, summed difference score (SDS), and LV ejection fraction (EF) were evaluated. Two LVMD parameters, phase standard deviation (PSD) and phase histogram bandwidth (PHB), were assessed in post-stress and rest MPI images. ΔPSD (post-stress PSD - rest PSD) and ΔPHB (post-stress PHB - rest PHB) were calculated to measure stress-induced changes in LVMD., Results: In all the groups, mean post-stress LVMD parameters were lower as compared to LVMD parameters at rest. Post-stress PSD was significantly lower than rest PSD in all groups. Similar trend was noted with PHB values also, but it was statistically significant in the normal and ischemia group only. Post-stress worsening of at least one of the LVMD parameters was noted in 28 patients and all these patients had perfusion abnormalities. But on subgroup analysis, no difference was found in proportion of patients showing post-stress worsening of LVMD between ischemia (13.6%), infarct (25%), and mixed (23.6%) groups. No significant correlation was found between ΔPSD/ΔPHB and ΔLVEF/SDS in any group., Conclusion: LV mechanical dyssynchrony parameters are smaller in post-exercise stress as compared to rest on Tl-201 MPI, regardless of perfusion pattern. Stress-induced worsening of LV dyssynchrony was observed only in patients with perfusion abnormalities, but this is not related to the type of perfusion abnormality.

Bone marrow stem cells having myogenic potential are promising candidates for various cell-based therapies for myocardial disease. We present here images showing homing of technetium-99m (Tc-99m) hexamethylpropyleneamine oxime (HMPAO) labeled stem cells in the infarcted myocardium from a pilot study conducted to radio-label part of the stem cells in patients enrolled in a stem cell clinical trial for recent myocardial infarction.

Context: Patterns of myocardial fluoro-2-deoxyglucose (FDG) uptake with respect to duration of fasting and dietary modifications., Aim: We observed the effect of duration of fasting and diet on the myocardial uptake pattern of F-18 FDG in patients routinely referred for oncological evaluation and no previous history of Coronary Artery Disease (CAD)., Settings and Design: Prospective study., Subjects and Methods: A total of 153 patients (M: 81, F: 72; mean age: 47 ± 15 years; mean blood glucose level (mBG) 105 ± 23 mg/dl) were randomly divided in three groups. Group A: 4-6 h fasting; Group B: Overnight fasting (12-14 h); Group C: Low carbohydrate and fat rich diet for 2 days coupled with overnight fasting prior to the positron emission tomography (PET) scan. FDG uptake was classified as following: 1) homogeneous uptake, 2) heterogeneous uptake, and 3) 'no uptake' in the left ventricular (LV) myocardium. FDG PET study was performed as standard protocol for oncological conditions., Statistical Analysis Used: Descriptive statistics, Chi-square test or Fisher's exact test, and Spearman's rank correlation tests were applied., Results: We observed the 'no uptake' pattern in five (10%), 28 (55%), and 39 (77%), 'heterogeneous' pattern in 20 (39%), 14 (28%), and seven (14%), and 'homogeneous' pattern in 26 (51%), nine (18%), and five (10%) patients in Group A, B, and C, respectively. There was statistically significant difference of myocardial uptake pattern between group A and B (P < 0.0001), between group A and C (P < 0.0001), and between Group B and C (P = 0.023). The mBG was 102, 105, and 111 mg/dl in 'no uptake', heterogeneous, and homogeneous uptake pattern, respectively, (P = 0.103). Also, within each group the mBG was not related to the uptake pattern., Conclusion: Both restricted diet and duration of fasting play an important role in determining the pattern and suppression of myocardial F-18 FDG uptake. Overnight fasting and restricted diet together suppress myocardial FDG uptake more than overnight fasting alone, which suppresses uptake more than 4-h fasting.

Context: Arterial switch operation (ASO) has become the established treatment for correction of transposition of great arteries (TGA). Despite the immediate correction of abnormal hemodynamics, acute and delayed complications related to the coronaries may cause morbidity and mortality., Aims: We evaluated the incidence of perfusion abnormalities and safety of adenosine by stress-rest myocardial perfusion single-photon emission computed tomography (SPECT) [myocardial perfusion scintigraphy (MPS)] using Tc-99m Sestamibi (MIBI) in asymptomatic children post-ASO., Settings and Design: Prospective study., Materials and Methods: We conducted a prospective, single-institutional study where stress-rest MPS was performed on 10 children of age between 1.25 and 6 years. Two of the patients had additional ventricular septal defect, one patient had left ventricular outflow tract obstruction, and another had Taussig-Bing anomaly. All the patients underwent corrective surgery as a single-stage procedure at the age of 176 ± 212 days (range 9-560 days). Adenosine was administered at a rate of 140 μg/kg/min intravenously as continuous infusion for duration of 6 min., Statistical Analysis Used: All the continuous variables were summarized as mean ± standard deviation, or range and median. Mann-Whitney test for unpaired data and Wilcoxon Rank test for paired samples were used., Results: The average increase in heart rate over the basal heart rate after adenosine stress was 59.7 ± 17.0%. No acute or remote complications were observed in any case. None of the patients demonstrated myocardial perfusion defects, either at rest or after adenosine stress., Conclusions: MPS post-adenosine induced vasodilatation is safe and feasible in patients of ASO for transposition of great arteries. One-stage repair, implantation of excised coronary buttons within neo-aortic sinus, and minimal or no mobilization of proximal coronaries may eliminate the occurrence of perfusion defects in patients of corrected TGA.

Objective: The aim of this study was to evaluate the prognostic significance of qualitative and quantitative F-fluorodeoxyglucose (F-FDG) PET-computed tomography (PET-CT) parameters in patients with recurrent cervical carcinoma., Methods: Twenty-six patients (age: 44 ± 10.1 years) with histologically proven recurrent carcinoma of the cervix (squamous, 21; adenocarcinoma, five) were prospectively enrolled and they underwent F-FDG PET-CT before salvage therapy. The qualitative parameters included for analysis were vaginal involvement, regional nodal metastasis, and distant metastasis on PET-CT. The quantitative PET-CT parameters included were standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Cutoff values were determined using receiver operating characteristic curve analysis. A Kaplan-Meier analysis was carried out to compare survival among groups. Impact of PET-CT parameters on progression-free survival (PFS) and overall survival (OS) was evaluated using Cox proportional hazard regression., Results: On PET-CT, vaginal involvement was seen in 16 patients, regional nodal metastasis in 12 patients, and distant metastasis (node and lung) in 11 patients. The mean SUVmax was 6.8 ± 4, MTV was 8.2 ± 12.8 ml, and TLG was 49.6 ± 108.4 ml. On multivariate analysis, SUVmax of up to 4.9 [hazard ratio (HR): 0.026, confidence interval (CI): 0.002-0.268, P=0.002] and distant metastasis (HR: 18.88, CI: 2.14-166.24, P=0.008) were independent predictors of PFS. On multivariate analysis, SUVmax greater than 9 (HR: 19.25, CI: 2.15-172.17, P=0.008) and distant metastasis (HR: 33.88, CI: 2.17-526.61, P=0.012) were also independent predictors of OS. MTV, TLG, and regional node involvement evaluated using PET-CT were found to be significant on univariate analysis but not on multivariate analysis., Conclusion: SUVmax and the presence of distant metastasis on F-FDG PET-CT are independent predictors of PFS and OS in patients with recurrent cervical carcinoma.

Background: Data on normal parameters of cardiac mechanical synchrony is limited, variable and obtained from small cohorts till date. In most studies, software used for such assessment has not been mentioned. The aim of study is to establish normal values of mechanical synchrony with equilibrium radionuclide angiography (ERNA) in a larger population using commercially available software., Methods: We retrospectively analysed ERNA studies of 108 patients having low pretest likelihood of coronary artery disease, no known history of cardiac disease, normal electrocardiogram and whose ERNA studies were considered normal by experienced observers. In addition, ten patients diagnosed with dilated cardiomyopathy (DCM) and having LVEF ≤ 40% underwent ERNA. Fourier first harmonic analysis of phase images was used to quantify synchrony parameters using commercially available software (XT-ERNA). Intraventricular synchrony for each ventricle was measured as the standard deviation of the LV and RV mean phase angles (SD LVmPA and SD RVmPA, respectively). Interventricular synchrony was measured as LV-RVmPA. Absolute interventricular delay was calculated as absolute difference between LV and RVmPA (without considering ± sign). All variables were expressed in milliseconds (ms) and degree (°). Intra-observer and inter-observer variabilities were assessed. Cut-off values for parameters were calculated from the normal database, and validated against patient group., Results: On phase analysis, LVmPA was observed to be 343 ± 48.5 milliseconds (174.7° ± 18.5°), SD LVmPA was 16.3 ± 5.4 milliseconds (8.2° ± 2.5°), RVmPA was 339 ± 50.4 milliseconds (171.8° ± 18.5°) and SD RVmPA was 37.3 ± 15.7 milliseconds (18.7° ± 7.2°). LV-RVmPA was observed to be 3.9 ± 21.7 milliseconds (2.9° ± 9.6°) and absolute interventricular delay was 16.3 ± 14.8 milliseconds (7.9° ± 6.1°). The cut-off values for the presence of dyssynchrony were estimated as SD LVmPA > 27.1 milliseconds (>13.2°), SD RVmPA > 68.7 milliseconds (>33.1°) and LV-RVmPA > 47.3 milliseconds (>22.1°). There was no statistically significant intra-observer or inter-observer variability. Using these cut offs, 9 patients with DCM showed the presence of left intraventricular dyssynchrony, 5 had right intraventricular dyssynchrony and 2 had interventricular dyssynchrony., Conclusions: ERNA phase analysis offers an objective and reproducible tool to quantify cardiac mechanical synchrony using commercially available software and can be used in routine clinical practice to assess mechanical dyssynchrony.

Objective: The goal of this study was to compare Emory Cardiac Toolbox (ECTb), quantitative gated SPECT (QGS), four-dimensional single photon emission computed tomography (4D-MSPECT) and Myometrix cardiac software programs for the assessment of left ventricular ejection fraction (LVEF) using 99mTc-tetrofosmin-gated SPECT/CT [myocardial perfusion SPECT (MPS)] and correlate them with the LVEF values derived from equilibrium radionuclide ventriculography (ERNV) in patients with known/suspected coronary artery disease (CAD)., Materials and Methods: A total of 109 patients (80 men, 29 women) were recruited into the study. Fifty-five patients had known CAD and 54 were referred with suspicion of CAD. All the patients underwent ERNV and MPS as per the standard protocol. ERNV was processed using the vendor-provided 'EF analysis' and gated MPS was processed using individual software programs., Results: The mean LVEF on ERNV was 47.9 ± 15.5%. The mean LVEF values for ECTb, QGS, 4D-MSPECT and Myometrix were 51.5 ± 19.6, 51.0 ± 18.6, 57.1 ± 19.3 and 49.7 ± 19%, respectively. On correlation analysis, a very strong positive correlation was observed between LVEF values derived by ERNV and those derived by the MPS software programs: ECTb (r=0.842, P<0.0001), QGS (r=0.835, P<0.0001), 4D-MSPECT (r=0.830, P<0.0001) and Myometrix (r=0.875, P<0.0001). Significant correlation was also seen for LVEFs among the four software programs. Normal cutoff values for ejection fraction on ECTb, QGS, 4D-MSPECT and Myometrix were 56, 52, 54 and 51%, respectively, using a 50% or more cutoff value on ERNV., Conclusion: A strong correlation was observed among ECTb, QGS, 4D-MSPECT and Myometrix software programs when compared with ERNV and also between them for assessment of LVEF. However, there are subtle differences in the objective values of ejection fraction generated by individual software, which must be taken into account for clinical studies.