Publications by authors named "T S Nagaraj"

16 Publications

Maternal and Fetal Vascular Lesions of Malperfusion in the Placentas Associated with Fetal and Neonatal Death: Results of a Prospective Observational Study.

Am J Obstet Gynecol 2021 Jun 7. Epub 2021 Jun 7.

Columbia University, New York NY USA.

Background: Fetal death, one of the major adverse pregnancy outcomes, is especially common in low and middle-income countries. Placental lesions may play an important role in the etiology of fetal and possibly neonatal death. Prior research relating placental lesions to fetal death causation was often hindered by the lack of agreement on a placental classification scheme. The Amsterdam Consensus statement, published in 2016, focused attention on malperfusions in the maternal and fetal placental circulations.

Objectives: Our purpose was to investigate the relationships of placental maternal vascular (MVM) and fetal vascular malperfusion (FVM) to fetal and neonatal death with a focus on the most important maternal clinical conditions in the pathway to fetal and neonatal death; maternal hypertension, antepartum haemorrhage and decreased fetal growth.

Study Design: This was a prospective, observational cohort study conducted at two Asian sites. Data collected included clinical history, gross and histologic evaluation of the placenta, and a number of other investigations to determine cause of death. The placenta was evaluated at both sites using the Amsterdam Consensus framework. We estimated the risk of placental MVM and FVM among fetal and neonatal deaths.

Results: Between July 2018 and January 2020 in India and Pakistan, 814 women with a fetal death, 618 with a preterm live birth and subsequent neonatal death, and 201 term live births, all with a placenta available for study, provided consent. The prevalence of MVM was higher in placentas of fetal deaths (58.4%) and preterm neonatal deaths (31.1%) compared to the term live births (15.4%). Adjusting for site, MVM had a RR of 3.88 (95% CI 2.70-5.59) among fetal deaths vs. term live births and a RR of 2.07 (95% CI 1.41-3.02) for preterm neonatal deaths vs. term live births. Infarcts and distal villous hypoplasia were the most common histological components of MVM. FVM was found less frequently in the placentas of fetal deaths (19.0%) than was MVM (58.4%). However, there were higher frequencies of FVM in fetal death placentas (19.0%) than in placentas from neonatal deaths (8.3%) or in the term live birth placentas (5.0%). Adjusting for site, FVM had a RR of 4.09 (95% CI 2.15-7.75) among fetal deaths vs. term live births and RR 1.77 (95% CI 0.90-3.49) for preterm neonatal deaths vs. term live births. There was a higher incidence of MVM in cases of maternal hypertension (71.4%), SGA (69.9%) and antepartum hemorrhage (59.1%) compared to the incidence of MVM in fetal deaths with none of these conditions (43.3%). There were no significant differences in the occurrence of FVM among the four clinical categories.

Conclusion(s): Histological examination of the placenta, especially for malperfusion disorders, is crucial in elucidating pathways to fetal death and likely for neonatal death in preterm infants. Possibly more important is the potential to focus on placental MVM and FVM during pregnancy as a means to identify fetuses at risk and to reduce the risk of fetal death by early delivery. It is our additional hope that the increased risk of fetal and neonatal death in these pregnancies can be reduced by development of an intervention to reduce the likelihood of developing MVM and/or FVM in the first place.
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June 2021

Atypical Teratoid/Rhabdoid Tumor: Revisiting Histomorphology and Immunohistochemistry With Analysis of Cyclin D1 Overexpression and Amplification.

Int J Surg Pathol 2021 Apr 24;29(2):155-164. Epub 2020 Jul 24.

29436Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.

. Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignant pediatric brain tumor, characterized by inactivation of INI1/hSNF5 gene and loss of its protein. We studied the histomorphological and immunohistochemical spectrum of this tumor including cyclin D1 expression and gene amplification. . Cases with INI1 loss by immunohistochemistry (IHC; from 2005 to 2018) were retrieved, reviewed, and evaluated for cyclin D1 expression by additional IHC and fluorescence in situ hybridization for genes. . A total of 66 cases were identified. Age ranged from 1 to 20 years (≤3 years, 44 cases; >3 years, 22). Male to female ratio was 1.7:1. Tumor locations were as follows: posterior fossa: 30; supratentorial: 31; spinal: 5. AT/RT in patient ≤3 years was frequently located in the posterior fossa, composed of primitive embryonal morphology ( = .02), rarely had ample rhabdoid cells ( = .05), and had a negative impact on overall survival ( = .04). The rhabdoid cells was a conspicuous component of posterior fossa tumors compared with the supratentorial ones ( = .06). The supratentorial tumors ( = .06), absence of rhabdoid cells ( = .06), and the presence of immunological divergent differentiation ( = .11) had a comparatively better outcome. Cyclin D1 overexpression (n = 46) was noted in 32 cases and was frequently seen in the posterior fossa tumors ( = .02). (n = 42) amplification was seen in 1 case and the (n = 42) amplification in none. . AT/RT can occur in the noninfantile age group, at nonconventional sites and frequently overexpress cyclin D1. The alterations are almost nonexistent in AT/RT.
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April 2021

Intra-observer and inter-observer variability in two grading systems for oral epithelial dysplasia: A multi-centre study in India.

J Oral Pathol Med 2020 Oct 9;49(9):948-955. Epub 2020 Jul 9.

Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, WHO Collaborating Centre for Oral Cancer, London, UK.

Background: The presence and grading of oral epithelial dysplasia (OED) are considered the gold standard for predicting the malignant risk of oral potentially malignant disorders. However, inter-observer and intra-observer agreement in the context of reporting on OED grading has been reputedly considered unreliable.

Methods: We undertook a multi-centre study of six Indian oral pathologists to assess variations in reporting OED using the World Health Organization (WHO; 2005) system and also the recently introduced binary system. The observer variability was assessed with the use of kappa statistics.

Results: The weighted kappa intra-observer agreement scores improved (κ  = 0.5012) on grouping by two grades as no and mild dysplasia versus moderate and severe dysplasia compared to binary grading system (κ = 0.1563) and WHO grading system (κ  = 0.4297). Poor to fair inter-observer agreement scores were seen between the principal investigator (PI) and the other five observers using the WHO grading system (κ = 0.051-0.231; κ  = 0.145 to 0.361; 35% to 46%) and binary grading system (κ = 0.049 to 0.326; 50 to 65%).

Conclusions: There is considerable room for improvement in the assessment of OED using either system to help in standardised reporting. The professional pathology organisations in India should take steps to provide external quality assessment in reporting OED among oral and general pathologists who are engaged in routine reporting of head and neck specimens.
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October 2020

Risk Versus Benefit of Combined Aspirin and Warfarin Therapy in Patients With Atrial Fibrillation.

J Pharm Pract 2020 Apr 15:897190020916638. Epub 2020 Apr 15.

Ohio State University Wexner Medical Center, Columbus, OH, USA.

Purpose: Guidelines have differing recommendations for aspirin use in patients with an indication for anticoagulation. The purpose of this study was to evaluate the incidence of major bleeding and thromboembolic events (TEs) in patients with atrial fibrillation (AF) receiving warfarin alone (monotherapy group) versus warfarin plus aspirin (combination therapy group).

Methods: This was a retrospective, cohort study including patients from a pharmacist-run anticoagulation clinic. Inclusion criteria were patients with AF receiving anticoagulation between January 2013 and January 2014 observed over 5 years.

Results: One hundred forty-two patients were included in the combination group versus 89 in monotherapy group. In the combination group, 60 (42.3%) patients were on aspirin for no apparent indication, 19 (13.4%) had stable coronary artery disease and diabetes, and 26 (18.3%) had diabetes alone. Major bleeding occurred in 21 (14.9%) patients in the combination group versus 7 (7.9%) patients in the monotherapy group (odds ratio [OR] = 2.02, 95% confidence interval [CI]: 0.78-5.91; = .17). TE occurred in 10 (7%) patients in the combination group versus 4 (4.5%) in the monotherapy group (OR = 1.61, 95% CI: 0.44-7.24; = .57). There was no significant difference in bleeding ( = .85) or TE ( = .37) rates between aspirin indications in the combination group.

Conclusion: Combination therapy versus monotherapy may increase bleeding risk with little benefit in decreasing AF-related stroke or cardiovascular events.
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April 2020

Comparison and Clinical Evaluation of Two Pit and Fissure Sealants on Permanent Mandibular First Molars: An Study.

J Contemp Dent Pract 2019 Oct 1;20(10):1151-1158. Epub 2019 Oct 1.

Department of Paedodontics and Preventive Dentistry, Government Dental College, Alappuzha, Kerala, India.

Aim: The aim of the study was to compare and evaluate the clinical efficacy of a microfilled pit and fissure sealant and a nanofilled pit and fissure sealant at 3, 6, and 12 months of interval.

Materials And Methods: Samples consisting of 55 healthy 8- to 12-year-old children with deep pits and fissures in mandibular first permanent molars were selected for the study. It was a split mouth design and randomized clinical trial. A total of 110 mandibular first molars were divided into two groups of 55 each: group I Fissurit FX sealant and group II Grandioseal nanofilled fissure sealant. The sealed teeth were clinically evaluated at 3, 6, and 12 months of interval to assess marginal adaptation, sealant retention, fissure caries development, roughness of sealant surface, and change of color around the sealant.

Results: The results showed that both Fissurit FX and Grandioseal pit and fissure sealants were effective in preventing dental caries. Marginal adaptation was significantly better with Fissurit FX when compared to Grandioseal pit and fissure sealant. There was no difference in sealant retention between the two groups. The surface roughness of Fissurit FX was high when compared to that of Grandioseal. Statistical analysis was done using the Chi-squared test for intra-group comparison and Fisher's exact test for inter-group comparison. Results were considered statistically significant if ≤ 0.05.

Conclusion: Fissurit FX and Grandioseal pit and fissure sealants provided similar caries preventive effects and there was no difference in retention of sealants over a period of 1 year. However, surface roughness was better with Grandioseal fissure sealants.

Clinical Significance: This study is significant because there is limited evidence about the efficacy of nanofilled pit and fissure sealants . It will also provide dental practitioners an insight into the clinical efficacy of nanofilled pits and fissure sealant when compared to micro-filled sealant enabling them to make the right choice for the betterment of their dental practice. How to cite this article: Smitha M, Paul ST, Nagaraj T, Comparison and Clinical Evaluation of Two Pit and Fissure Sealants on Permanent Mandibular First Molars: An Study. J Contemp Dent Pract 2019;20(10):1151-1158.
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October 2019