Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disorder of older adults char... more Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disorder of older adults characterized by the clonal expansion of cytotoxic T/natural killer cells due to constitutive pro-survival signaling. In recent years, it has become clear that cytokines and their receptors are aberrantly expressed in LGLL cells. The exact initiation process of LGLL is unknown, although several cytokine-driven mechanisms have emerged. Elevated levels of several cytokines, including interleukin-15 (IL-15) and platelet-derived growth factor (PDGF), have been described in LGLL patients. Evidence from humans and animal models has shown that cytokines may also contribute to the co-occurrence of a wide range of autoimmune diseases seen in patients with LGLL. The goal of this review is to provide a comprehensive analysis of the link between cytokines and pro-survival signaling in LGLL and to discuss the various strategies and research approaches that are being utilized to study this link. This revi...
Background: To avoid cervical scar in thyroid surgery, various approaches have been proposed. The... more Background: To avoid cervical scar in thyroid surgery, various approaches have been proposed. The commonly used approach is combined axillo-breast approach (ABA). However, trans-orovestibular approach (TOVA) is getting popular. The aim of this study is to compare surgical outcomes of patients who underwent endoscopic hemithyroidectomy (EHT) by either ABA or TOVA. Patients and Methods: This was a retrospective analysis of clinical data of patients who underwent EHT from January 2013 to December 2018. Patients were divided into two groups: Group A – through ABA and Group B – through TOVA. Results: A total of eighty patients underwent EHT in Group A and 25 in Group B. In both groups, most patients were female (male: female = 1:4.7 in Group A and 1:7.33 in Group B, P = 0.515). In both groups, there was no difference in age (the mean age was 33.44 ± 10.44 years in Group A and 33.04 ± 14.01 years in Group B, P = 0.391) and in size of the nodule (Group A – 3.91 ± 1.17 cm and Group B – 3.6 ± 1.39 cm, P = 0.228). The operating time was significantly less in Group B (Group A – 152.25 ± 30.19 mins and Group B – 126.80 ± 22.94 mins, P ≤ 0.01). The post-operative hospital stay was significantly less in Group B (mean 3.17 ± 0.97 days in Group A and 2.24 ± 0.60 days in Group B, P ≤ 0.01). Conclusion: TOVA is associated with shorter operating time and hospital stay with comparable outcomes. Cosmetic outcome is excellent in TOVA, however requires further subjective evaluation.
Higher mobilization of the loans by the Banks indicate the higher level of facilitation and suppo... more Higher mobilization of the loans by the Banks indicate the higher level of facilitation and support. However higher levels of default indicates the opposite. This study after the review of over 20 empirical articles, attempts to use the Reserve Bank of India information to assess the credit portfolio service levels of different types of banks in India. The study attempts to examine the case using the 1996-2012 RBI data set to understand the credit portfolio choice using the secondary data. The study finds the shifting stance of the credit portfolio preferences over the years from the old PSU banks to the PSU banks. Despite the lower start the new generation PSU banks are able to contain the risks.
Objective: The relationship of thyroid dysfunction and autoimmunity with breast cancer (BC) conti... more Objective: The relationship of thyroid dysfunction and autoimmunity with breast cancer (BC) continues to be contentious. The primary aim of this study was to estimate the prevalence of thyroid dysfunctions and autoimmunity in BC patients, and the secondary aims were to investigate the relationship of thyroid dysfunction with the clinicopathological profile of and therapy received by BC patients. Materials and methods: This was a single-center prospective case-control study (March 2015-May 2017). Women with BC (n = 191), age-matched healthy controls (n = 166) and malignant controls (patients with cervical cancer, n = 87) were enrolled. Basal serum free thyroxin (fT4), thyrotropin (TSH) and anti-thyroid peroxidase (TPO) antibody levels were measured in all three groups; fT4, TSH and TPO measures were repeated after chemotherapy and at the 1-year follow-up (one year after diagnosis) in the BC patients. Results: The prevalence of overall hypothyroidism and autoimmunity (p = 0.106) did not differ significantly between the three groups, but the rate of clinical hypothyroidism was significantly higher in the BC group than in the healthy control group and the malignant control group (12.2% vs. 3.0% vs. 4.6%, respectively; p = 0.001). BC patients had significantly lower mean basal TSH concentrations than the healthy controls (p = 0.017). The postchemotherapy TSH concentrations were significantly lower (p = 0.001), and the fT4 concentrations were higher, albeit not significantly (p = 1.00), than the respective basal concentrations. The reverse was true for the follow-up values, in which the TSH (p = 1.00) values were higher and the fT4 (p = 0.03) concentrations were lower than the respective basal concentrations. An additional 6% of the BC patients developed clinical hypothyroidism during follow-up. Hypothyroid (p = 0.02) and TPO-positive (p = 0.004) patients had significantly smaller tumors, but their other clinicopathological features were comparable to those without thyroid dysfunction. Conclusions: The prevalence of clinical hypothyroidism requiring thyroxine replacement was significantly high in BC patients and increased further during follow-up. Hence, BC patients should be considered a high-risk group that should receive routine screening for hypothyroidism.
Purpose. The primary aim of this study was to determine the incidence of estrogen receptor α (ERα... more Purpose. The primary aim of this study was to determine the incidence of estrogen receptor α (ERα), estrogen receptor β (ERβ), and human epidermal growth factor receptor 2 (HER-2) expression in various subtypes of thyroid carcinoma (TC) of follicular origin and the secondary aim was to correlate the expression with various clinicopathologic prognostic factors. Methods. Immunohistochemistry analysis was performed on archival paraffin-embedded tissue sections (1991–2016). ERα, ERβ, and HER-2 expressions were correlated with clinicopathologic prognostic factors, disease recurrence, and overall survival (OS). Results. A total of 264 TC patients were included in the study. Incidences of ERα, ERβ, and HER-2 were 8.1 vs 16.3 vs 13.9% p=0.15, 26.6 vs 11.5 vs 36.1% p=0.002, and 12.9 vs 2.9 vs 0% p=0.003 in papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and poorly differentiated thyroid carcinoma (PDTC), respectively. Overall ERα had significant correlation with distan...
Thrombosis of the dural sinus and/or cerebral veins (cerebral venous thrombosis [CVT]) is an unco... more Thrombosis of the dural sinus and/or cerebral veins (cerebral venous thrombosis [CVT]) is an uncommon form of stroke, usually affecting young individuals. Early diagnosis and timely institution of appropriate treatment is usually associated with a good outcome. However, its non-specific and extremely varied clinical presentation makes it difficult to diagnose. In this article, we review the etiology, clinical features, diagnostic tools, and mainstay therapy of CVT with recent advancements to help clinicians keep a high degree of suspicion for this disease in appropriate clinical scenarios. We also provide two clinical case scenarios from our hospital as an example of its diverse presentation.
International Journal of Telemedicine and Clinical Practices, 2019
This study was conducted to analyse if in a resource constraint country, social media can provide... more This study was conducted to analyse if in a resource constraint country, social media can provide a feasible, acceptable and cost effective mode of surgical care in post-operative period? This was a prospective study conducted at
Purpose Poorly differentiated thyroid carcinoma (PDTC) patients have worse outcomes than patients... more Purpose Poorly differentiated thyroid carcinoma (PDTC) patients have worse outcomes than patients with differentiated thyroid carcinoma (DTC), but the implication of poorly differentiated areas (PDAs) noted in DTC is not very well understood. The aim of the present study was to compare the clinicopathologic profiles and outcomes of PDTC and DTC with PDA. Methods A total of 142 patients, managed at out center between September 1989 and June 2016, were enrolled in this retrospective study. Histology was reviewed, and the patients were divided in the following three groups: poorly differentiated carcinoma [PDTC; group 1 (n = 27)]; papillary thyroid carcinoma with PDA [PTC with PDA; group 2 (n = 27)]; and follicular thyroid carcinoma with PDA [FTC with PDA; group 3 (n = 88)]. Clinico-pathologic profiles and outcomes were compared between the three groups. The Kaplan-Meier method was used for survival analysis. The log-rank test and Cox regression model were used to perform univariate and multivariate analyses of the factors affecting the overall survival (OS). Results The clinical profiles of the three groups were comparable except for significantly less incidence of lymph node involvement (p = 0.002) and extra-thyroidal invasion (p = 0.002) and higher incidence of distant metastases (p = 0.01) in group 3. Median follow-up period was 47.5 months, and 5-and 10-year OS were 57 and 14%, respectively. There was no difference between OS of PDTC and DTC (group 2 + 3), but group 3 patients had significantly better OS than group 2 patients. Univariate analysis revealed that tumor size (p = 0.04), extra-thyroidal invasion (p = 0.05), lateral compartment lymphadenopathy (p = 0.002), distant metastases (p = < 0.001), absence of encapsulation (p = 0.03), and > 75% PDA (p = 0.001) were associated with worse OS. Multivariate analysis revealed tumor size (p = 0.005), distant metastases (p = 0.012), lymphadenopathy (p = 0.017), TNM staging (p = < 0.001), and PDA > 75% (p = < 0.001) to be significantly associated with OS. Conclusion There is no difference in the outcomes of PDTC and DTC with PDA. However, PTC patients with PDA have worse outcomes than FTC patients with PDA. Irrespective of tumor type, the presence of more than 75% PDA in DTC is associated with adverse outcomes.
C-cell hyperplasia (CCH) is characterized by increased mass of C-cells and has been identified as... more C-cell hyperplasia (CCH) is characterized by increased mass of C-cells and has been identified as a precursor condition for medullary thyroid carcinoma (MTC). Varying proportion of MTCs is associated with CCH in different studies. This could be due to the lack of uniformity of the definitions and techniques used to identify CCH in these studies. This study aims to study the occurrence, clinicopathological, and immunohistochemical features of CCH in MTC diagnosed during a 22-year period at a tertiary care center in North India and to review the available literature on CCH. Eighty-seven consecutive cases of MTC were included in the study. Histological evaluation for the presence of CCH and neoplastic CCH was performed. Confirmation of CCH was done by immunohistochemistry for calcitonin and chromogranin. The presence of neoplastic CCH was correlated with clinical factors and prognostic factors. Of 87 cases of MTC included in the study, 71 (82%) patients were sporadic and 16 (18%) had f...
The concept of short stay thyroidectomy has been tested and in practice in the developed world; t... more The concept of short stay thyroidectomy has been tested and in practice in the developed world; the same has not been replicated in countries with limited resources due to lack of organized healthcare system. So, in this study, we tried to analyze if short stay thyroid surgery can be performed in a cost-effective way in developing countries and also if the endocrine surgical trainee can deliver these services safely. The study was conducted prospectively from January 2013 to July 2014, at Department of Endocrine Surgery, SGPGIMS, Lucknow, India. Study group included patients undergoing short stay hemithyroidectomy whereas matched patients who qualified for inclusion criteria but did not undergo short stay surgery due to various reasons constituted control group. Outcome in both the groups was compared in terms of complication rates, cost benefit, and patient satisfaction. Subgroup analysis was also done for trainee versus consultant performed short stay thyroid surgery. A total of 4...
Acute myeloid leukemia (AML) can evade the mouse and human innate immune system by suppressing na... more Acute myeloid leukemia (AML) can evade the mouse and human innate immune system by suppressing natural killer (NK) cell development and NK cell function. This is driven in part by the overexpression of microRNA (miR)-29b in the NK cells of AML patients, but how this occurs is unknown. In the current study, we demonstrate that the transcription factor aryl hydrocarbon receptor (AHR) directly regulates miR-29b expression. We show that human AML blasts activate the AHR pathway and induce miR-29b expression in NK cells, thereby impairing NK cell maturation and NK cell function, which can be reversed by treating NK cells with an AHR antagonist. Finally, we show that inhibition of constitutive AHR activation in AML blasts lowers their threshold for apoptosis and decreases their resistance to NK cell cytotoxicity. Together, these results identify the AHR pathway as one molecular mechanism by which AML impairs NK cell development and function. The results lay the groundwork in establishing ...
Total thyroidectomy (TT) with a uniform technique of capsular dissection (CD) is the preferred te... more Total thyroidectomy (TT) with a uniform technique of capsular dissection (CD) is the preferred technique worldwide. The aim of study is to analyze the impact of uniform technique of CD for done as primary surgery at an endocrine surgery training centre. Retrospective review from 1995 to 2009. Data collected from hospital records and follow-up. One thousand and thirty-eight cases were included, with mean age 42.91 ± 13.48 years; male:female - 1:2.2; mean duration of goiter - 99.83 ± 105.1 months; 67.8% were euthyroid and 30.7% - hyperthyroid at initial presentation; 35.5% were malignant. Surgery includes TT alone - 77.7% and TT with lymph nodes dissection - 22.3%; sternotomy required in 1.2% and thoracotomy in 0.1%; tracheomalacia present in 3.9%; however, tracheostomy required in 4.5% and parathyroid autotransplantation in 21%; Peroperative mean gross gland weight was 124.34 ± 129.85 g. Complications include hypocalcemia (temporary - 35.9%; permanent - 1.3%); recurrent laryngeal ner...
• Paradoxically higher NK-cell activity in CTCL patients is associated with increased expression ... more • Paradoxically higher NK-cell activity in CTCL patients is associated with increased expression of phosphorylated STAT5. • These highly effective NK cells are associated with poor prognosis in patients with leukemic CTCL.
Naunyn-Schmiedeberg's archives of pharmacology, Jan 6, 2018
The present study was designed to investigate the oral bioavailability, metabolism, tissue dispos... more The present study was designed to investigate the oral bioavailability, metabolism, tissue disposition and excretion of 16α-hydroxycleroda-3, 13(14) Z -dien-15, 16-olide (4655K-09), a novel HMG-CoA reductase inhibitor in male Sprague Dawley (SD) rats. Tissue distribution, oral bioavailability and excretion studies of 4655K-09 were carried out in male SD rats through oral administration at active dose of 25 mg/kg. In vitro metabolism studies were carried out in different rat tissues S9 fractions to evaluate primary organs responsible for conversion of parent 4655K-09 to its major active metabolite K-9T. The quantification of both parent and metabolite in different biological matrices was performed using LC-MS/MS method. The oral bioavailability of 4655K-09 was found to be 30% in male SD rats. The biodistribution study was illustrated in terms of tissue to plasma area under curve (AUC) ratio (K) revealed the preferential distribution of 4655K-09 and K-9T to target site, i.e. liver. In...
KMT2A partial tandem duplication occurs in approximately 5-10% of patients with acute myeloid leu... more KMT2A partial tandem duplication occurs in approximately 5-10% of patients with acute myeloid leukemia and is associated with adverse prognosis. KMT2A wild type is epigenetically silenced in KMT2A partial tandem duplication; re-expression can be induced with DNA methyltransferase and/or histone deacetylase inhibitors in vitro, sensitizing myeloid blasts to chemotherapy. We hypothesized that epigenetic silencing of KMT2A wildtype contributes to KMT2A partial tandem duplication-associated leukemogenesis and pharmacologic re-expression activates apoptotic mechanisms important for chemo-response. We developed a regimen for this unique molecular subset but due to relatively low frequency of KMT2A partial tandem duplication, this dose finding study was conducted in relapsed/refractory disease regardless of molecular subtype. Seventeen adults (< age 60) with relapsed/refractory acute myeloid leukemia were treated on study. Patients received decitabine 20 milligrams/meter2 daily on days ...
Occult follicular thyroid carcinoma (FTC) presenting as distant metastases is a rare occurrence. ... more Occult follicular thyroid carcinoma (FTC) presenting as distant metastases is a rare occurrence. However, despite being occult in majority of these cases, primary tumor can be detected on thyroid imaging or during surgery. Here, we present an extremely rare case of an occult FTC with overt skeletal metastases in which primary tumor was discernible only on microscopic examination.
Xenobiotica; the fate of foreign compounds in biological systems, Jan 22, 2018
1) 16α-hydroxycleroda-3, 13(14) Z -dien-15, 16-olide (4655K-09 or K-09) is a novel clerodane dite... more 1) 16α-hydroxycleroda-3, 13(14) Z -dien-15, 16-olide (4655K-09 or K-09) is a novel clerodane diterpene lactone reported for its anti hyperlipidemic efficacy. The objective of the present study was to investigate the probable reversible metabolism of 4655K-09 and evaluate its effects on pharmacokinetic (PK) properties. 2) The PK studies were carried out through intravenous (IV) bolus administration of 4655K-09 and K-9T in mice at a dose of 3, 6, and 12 mg/kg separately. The oral PK study of 4655K-09 were carried out at therapeutic dose of 25 mg/kg. 3) The % AUC of metabolite converted to parent upon its administration [Formula: see text] was found to be 27.28 ± 2.67. The multi-compartmental interconversion model defined reversible and irreversible clearances along with volumes of distribution for parent and metabolite. The results emphasized that hydrolysis of lactone to acid was more efficient than back conversion to parent due to greater extent of irreversible elimination of acid. ...
Most of the cases of PHPT in developing countries present in symptomatic stage, some even in very... more Most of the cases of PHPT in developing countries present in symptomatic stage, some even in very advanced stage but in recent years the trend seems to be changing. This has been corroborated from few recently published literature from developing countries. The scope of this study is to further carry out an in-depth analysis of various clinical and biochemical parameters of PHPT patients at a tertiary care center of northern India. In this retrospective analysis, a total of 333 patients with PHPT from the year 1990 to 2016 were studied. The study population was divided into three subgroups based on the time span; 1990-1999 (n = 34), 2000-2009 (n = 112), 2010-2016 (n = 187), and clinical and biochemical parameters were compared. The clinical presentation has evolved progressively with increase in older age group (35 vs 39 vs 43.85, p < 0.001), less patients with musculoskeletal symptoms (85.3 vs 76.8 vs 61%, p = 0.002) and less patients with severe bone disease (29.4 vs 10.7 vs 10...
The current standard-of-care for surgical staging of the axilla in clinically node-negative (N0) ... more The current standard-of-care for surgical staging of the axilla in clinically node-negative (N0) early breast cancers is sentinel lymph node biopsy (SLNB), which requires expensive radiopharmaceuticals for efficacious results. In-house produced low-cost radiopharmaceuticals may be the solution and have shown efficacy in earlier observational/pilot studies. We compared SLNB using in-house prepared radiopharmaceutical (Tc-Antimony-colloid) versus commercially marketed radiopharmaceutical (Tc-Sulphur-colloid) in this prospective randomized study. 78 clinically N0 early breast cancer patients (T1/2, N0 stages), undergoing primary surgery were prospectively randomized 1:1 into two groups; to receive SLNB using methylene blue, and eitherTc-Antimony colloid (Group-1) or Tc-Sulphur colloid (Group-2). Completion axillary dissection was done in all (validation SLNB). SLNB indices were compared between the groups. The groups were comparable with regard to age, stage, tumour size, hormone rece...
Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disorder of older adults char... more Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disorder of older adults characterized by the clonal expansion of cytotoxic T/natural killer cells due to constitutive pro-survival signaling. In recent years, it has become clear that cytokines and their receptors are aberrantly expressed in LGLL cells. The exact initiation process of LGLL is unknown, although several cytokine-driven mechanisms have emerged. Elevated levels of several cytokines, including interleukin-15 (IL-15) and platelet-derived growth factor (PDGF), have been described in LGLL patients. Evidence from humans and animal models has shown that cytokines may also contribute to the co-occurrence of a wide range of autoimmune diseases seen in patients with LGLL. The goal of this review is to provide a comprehensive analysis of the link between cytokines and pro-survival signaling in LGLL and to discuss the various strategies and research approaches that are being utilized to study this link. This revi...
Background: To avoid cervical scar in thyroid surgery, various approaches have been proposed. The... more Background: To avoid cervical scar in thyroid surgery, various approaches have been proposed. The commonly used approach is combined axillo-breast approach (ABA). However, trans-orovestibular approach (TOVA) is getting popular. The aim of this study is to compare surgical outcomes of patients who underwent endoscopic hemithyroidectomy (EHT) by either ABA or TOVA. Patients and Methods: This was a retrospective analysis of clinical data of patients who underwent EHT from January 2013 to December 2018. Patients were divided into two groups: Group A – through ABA and Group B – through TOVA. Results: A total of eighty patients underwent EHT in Group A and 25 in Group B. In both groups, most patients were female (male: female = 1:4.7 in Group A and 1:7.33 in Group B, P = 0.515). In both groups, there was no difference in age (the mean age was 33.44 ± 10.44 years in Group A and 33.04 ± 14.01 years in Group B, P = 0.391) and in size of the nodule (Group A – 3.91 ± 1.17 cm and Group B – 3.6 ± 1.39 cm, P = 0.228). The operating time was significantly less in Group B (Group A – 152.25 ± 30.19 mins and Group B – 126.80 ± 22.94 mins, P ≤ 0.01). The post-operative hospital stay was significantly less in Group B (mean 3.17 ± 0.97 days in Group A and 2.24 ± 0.60 days in Group B, P ≤ 0.01). Conclusion: TOVA is associated with shorter operating time and hospital stay with comparable outcomes. Cosmetic outcome is excellent in TOVA, however requires further subjective evaluation.
Higher mobilization of the loans by the Banks indicate the higher level of facilitation and suppo... more Higher mobilization of the loans by the Banks indicate the higher level of facilitation and support. However higher levels of default indicates the opposite. This study after the review of over 20 empirical articles, attempts to use the Reserve Bank of India information to assess the credit portfolio service levels of different types of banks in India. The study attempts to examine the case using the 1996-2012 RBI data set to understand the credit portfolio choice using the secondary data. The study finds the shifting stance of the credit portfolio preferences over the years from the old PSU banks to the PSU banks. Despite the lower start the new generation PSU banks are able to contain the risks.
Objective: The relationship of thyroid dysfunction and autoimmunity with breast cancer (BC) conti... more Objective: The relationship of thyroid dysfunction and autoimmunity with breast cancer (BC) continues to be contentious. The primary aim of this study was to estimate the prevalence of thyroid dysfunctions and autoimmunity in BC patients, and the secondary aims were to investigate the relationship of thyroid dysfunction with the clinicopathological profile of and therapy received by BC patients. Materials and methods: This was a single-center prospective case-control study (March 2015-May 2017). Women with BC (n = 191), age-matched healthy controls (n = 166) and malignant controls (patients with cervical cancer, n = 87) were enrolled. Basal serum free thyroxin (fT4), thyrotropin (TSH) and anti-thyroid peroxidase (TPO) antibody levels were measured in all three groups; fT4, TSH and TPO measures were repeated after chemotherapy and at the 1-year follow-up (one year after diagnosis) in the BC patients. Results: The prevalence of overall hypothyroidism and autoimmunity (p = 0.106) did not differ significantly between the three groups, but the rate of clinical hypothyroidism was significantly higher in the BC group than in the healthy control group and the malignant control group (12.2% vs. 3.0% vs. 4.6%, respectively; p = 0.001). BC patients had significantly lower mean basal TSH concentrations than the healthy controls (p = 0.017). The postchemotherapy TSH concentrations were significantly lower (p = 0.001), and the fT4 concentrations were higher, albeit not significantly (p = 1.00), than the respective basal concentrations. The reverse was true for the follow-up values, in which the TSH (p = 1.00) values were higher and the fT4 (p = 0.03) concentrations were lower than the respective basal concentrations. An additional 6% of the BC patients developed clinical hypothyroidism during follow-up. Hypothyroid (p = 0.02) and TPO-positive (p = 0.004) patients had significantly smaller tumors, but their other clinicopathological features were comparable to those without thyroid dysfunction. Conclusions: The prevalence of clinical hypothyroidism requiring thyroxine replacement was significantly high in BC patients and increased further during follow-up. Hence, BC patients should be considered a high-risk group that should receive routine screening for hypothyroidism.
Purpose. The primary aim of this study was to determine the incidence of estrogen receptor α (ERα... more Purpose. The primary aim of this study was to determine the incidence of estrogen receptor α (ERα), estrogen receptor β (ERβ), and human epidermal growth factor receptor 2 (HER-2) expression in various subtypes of thyroid carcinoma (TC) of follicular origin and the secondary aim was to correlate the expression with various clinicopathologic prognostic factors. Methods. Immunohistochemistry analysis was performed on archival paraffin-embedded tissue sections (1991–2016). ERα, ERβ, and HER-2 expressions were correlated with clinicopathologic prognostic factors, disease recurrence, and overall survival (OS). Results. A total of 264 TC patients were included in the study. Incidences of ERα, ERβ, and HER-2 were 8.1 vs 16.3 vs 13.9% p=0.15, 26.6 vs 11.5 vs 36.1% p=0.002, and 12.9 vs 2.9 vs 0% p=0.003 in papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and poorly differentiated thyroid carcinoma (PDTC), respectively. Overall ERα had significant correlation with distan...
Thrombosis of the dural sinus and/or cerebral veins (cerebral venous thrombosis [CVT]) is an unco... more Thrombosis of the dural sinus and/or cerebral veins (cerebral venous thrombosis [CVT]) is an uncommon form of stroke, usually affecting young individuals. Early diagnosis and timely institution of appropriate treatment is usually associated with a good outcome. However, its non-specific and extremely varied clinical presentation makes it difficult to diagnose. In this article, we review the etiology, clinical features, diagnostic tools, and mainstay therapy of CVT with recent advancements to help clinicians keep a high degree of suspicion for this disease in appropriate clinical scenarios. We also provide two clinical case scenarios from our hospital as an example of its diverse presentation.
International Journal of Telemedicine and Clinical Practices, 2019
This study was conducted to analyse if in a resource constraint country, social media can provide... more This study was conducted to analyse if in a resource constraint country, social media can provide a feasible, acceptable and cost effective mode of surgical care in post-operative period? This was a prospective study conducted at
Purpose Poorly differentiated thyroid carcinoma (PDTC) patients have worse outcomes than patients... more Purpose Poorly differentiated thyroid carcinoma (PDTC) patients have worse outcomes than patients with differentiated thyroid carcinoma (DTC), but the implication of poorly differentiated areas (PDAs) noted in DTC is not very well understood. The aim of the present study was to compare the clinicopathologic profiles and outcomes of PDTC and DTC with PDA. Methods A total of 142 patients, managed at out center between September 1989 and June 2016, were enrolled in this retrospective study. Histology was reviewed, and the patients were divided in the following three groups: poorly differentiated carcinoma [PDTC; group 1 (n = 27)]; papillary thyroid carcinoma with PDA [PTC with PDA; group 2 (n = 27)]; and follicular thyroid carcinoma with PDA [FTC with PDA; group 3 (n = 88)]. Clinico-pathologic profiles and outcomes were compared between the three groups. The Kaplan-Meier method was used for survival analysis. The log-rank test and Cox regression model were used to perform univariate and multivariate analyses of the factors affecting the overall survival (OS). Results The clinical profiles of the three groups were comparable except for significantly less incidence of lymph node involvement (p = 0.002) and extra-thyroidal invasion (p = 0.002) and higher incidence of distant metastases (p = 0.01) in group 3. Median follow-up period was 47.5 months, and 5-and 10-year OS were 57 and 14%, respectively. There was no difference between OS of PDTC and DTC (group 2 + 3), but group 3 patients had significantly better OS than group 2 patients. Univariate analysis revealed that tumor size (p = 0.04), extra-thyroidal invasion (p = 0.05), lateral compartment lymphadenopathy (p = 0.002), distant metastases (p = < 0.001), absence of encapsulation (p = 0.03), and > 75% PDA (p = 0.001) were associated with worse OS. Multivariate analysis revealed tumor size (p = 0.005), distant metastases (p = 0.012), lymphadenopathy (p = 0.017), TNM staging (p = < 0.001), and PDA > 75% (p = < 0.001) to be significantly associated with OS. Conclusion There is no difference in the outcomes of PDTC and DTC with PDA. However, PTC patients with PDA have worse outcomes than FTC patients with PDA. Irrespective of tumor type, the presence of more than 75% PDA in DTC is associated with adverse outcomes.
C-cell hyperplasia (CCH) is characterized by increased mass of C-cells and has been identified as... more C-cell hyperplasia (CCH) is characterized by increased mass of C-cells and has been identified as a precursor condition for medullary thyroid carcinoma (MTC). Varying proportion of MTCs is associated with CCH in different studies. This could be due to the lack of uniformity of the definitions and techniques used to identify CCH in these studies. This study aims to study the occurrence, clinicopathological, and immunohistochemical features of CCH in MTC diagnosed during a 22-year period at a tertiary care center in North India and to review the available literature on CCH. Eighty-seven consecutive cases of MTC were included in the study. Histological evaluation for the presence of CCH and neoplastic CCH was performed. Confirmation of CCH was done by immunohistochemistry for calcitonin and chromogranin. The presence of neoplastic CCH was correlated with clinical factors and prognostic factors. Of 87 cases of MTC included in the study, 71 (82%) patients were sporadic and 16 (18%) had f...
The concept of short stay thyroidectomy has been tested and in practice in the developed world; t... more The concept of short stay thyroidectomy has been tested and in practice in the developed world; the same has not been replicated in countries with limited resources due to lack of organized healthcare system. So, in this study, we tried to analyze if short stay thyroid surgery can be performed in a cost-effective way in developing countries and also if the endocrine surgical trainee can deliver these services safely. The study was conducted prospectively from January 2013 to July 2014, at Department of Endocrine Surgery, SGPGIMS, Lucknow, India. Study group included patients undergoing short stay hemithyroidectomy whereas matched patients who qualified for inclusion criteria but did not undergo short stay surgery due to various reasons constituted control group. Outcome in both the groups was compared in terms of complication rates, cost benefit, and patient satisfaction. Subgroup analysis was also done for trainee versus consultant performed short stay thyroid surgery. A total of 4...
Acute myeloid leukemia (AML) can evade the mouse and human innate immune system by suppressing na... more Acute myeloid leukemia (AML) can evade the mouse and human innate immune system by suppressing natural killer (NK) cell development and NK cell function. This is driven in part by the overexpression of microRNA (miR)-29b in the NK cells of AML patients, but how this occurs is unknown. In the current study, we demonstrate that the transcription factor aryl hydrocarbon receptor (AHR) directly regulates miR-29b expression. We show that human AML blasts activate the AHR pathway and induce miR-29b expression in NK cells, thereby impairing NK cell maturation and NK cell function, which can be reversed by treating NK cells with an AHR antagonist. Finally, we show that inhibition of constitutive AHR activation in AML blasts lowers their threshold for apoptosis and decreases their resistance to NK cell cytotoxicity. Together, these results identify the AHR pathway as one molecular mechanism by which AML impairs NK cell development and function. The results lay the groundwork in establishing ...
Total thyroidectomy (TT) with a uniform technique of capsular dissection (CD) is the preferred te... more Total thyroidectomy (TT) with a uniform technique of capsular dissection (CD) is the preferred technique worldwide. The aim of study is to analyze the impact of uniform technique of CD for done as primary surgery at an endocrine surgery training centre. Retrospective review from 1995 to 2009. Data collected from hospital records and follow-up. One thousand and thirty-eight cases were included, with mean age 42.91 ± 13.48 years; male:female - 1:2.2; mean duration of goiter - 99.83 ± 105.1 months; 67.8% were euthyroid and 30.7% - hyperthyroid at initial presentation; 35.5% were malignant. Surgery includes TT alone - 77.7% and TT with lymph nodes dissection - 22.3%; sternotomy required in 1.2% and thoracotomy in 0.1%; tracheomalacia present in 3.9%; however, tracheostomy required in 4.5% and parathyroid autotransplantation in 21%; Peroperative mean gross gland weight was 124.34 ± 129.85 g. Complications include hypocalcemia (temporary - 35.9%; permanent - 1.3%); recurrent laryngeal ner...
• Paradoxically higher NK-cell activity in CTCL patients is associated with increased expression ... more • Paradoxically higher NK-cell activity in CTCL patients is associated with increased expression of phosphorylated STAT5. • These highly effective NK cells are associated with poor prognosis in patients with leukemic CTCL.
Naunyn-Schmiedeberg's archives of pharmacology, Jan 6, 2018
The present study was designed to investigate the oral bioavailability, metabolism, tissue dispos... more The present study was designed to investigate the oral bioavailability, metabolism, tissue disposition and excretion of 16α-hydroxycleroda-3, 13(14) Z -dien-15, 16-olide (4655K-09), a novel HMG-CoA reductase inhibitor in male Sprague Dawley (SD) rats. Tissue distribution, oral bioavailability and excretion studies of 4655K-09 were carried out in male SD rats through oral administration at active dose of 25 mg/kg. In vitro metabolism studies were carried out in different rat tissues S9 fractions to evaluate primary organs responsible for conversion of parent 4655K-09 to its major active metabolite K-9T. The quantification of both parent and metabolite in different biological matrices was performed using LC-MS/MS method. The oral bioavailability of 4655K-09 was found to be 30% in male SD rats. The biodistribution study was illustrated in terms of tissue to plasma area under curve (AUC) ratio (K) revealed the preferential distribution of 4655K-09 and K-9T to target site, i.e. liver. In...
KMT2A partial tandem duplication occurs in approximately 5-10% of patients with acute myeloid leu... more KMT2A partial tandem duplication occurs in approximately 5-10% of patients with acute myeloid leukemia and is associated with adverse prognosis. KMT2A wild type is epigenetically silenced in KMT2A partial tandem duplication; re-expression can be induced with DNA methyltransferase and/or histone deacetylase inhibitors in vitro, sensitizing myeloid blasts to chemotherapy. We hypothesized that epigenetic silencing of KMT2A wildtype contributes to KMT2A partial tandem duplication-associated leukemogenesis and pharmacologic re-expression activates apoptotic mechanisms important for chemo-response. We developed a regimen for this unique molecular subset but due to relatively low frequency of KMT2A partial tandem duplication, this dose finding study was conducted in relapsed/refractory disease regardless of molecular subtype. Seventeen adults (< age 60) with relapsed/refractory acute myeloid leukemia were treated on study. Patients received decitabine 20 milligrams/meter2 daily on days ...
Occult follicular thyroid carcinoma (FTC) presenting as distant metastases is a rare occurrence. ... more Occult follicular thyroid carcinoma (FTC) presenting as distant metastases is a rare occurrence. However, despite being occult in majority of these cases, primary tumor can be detected on thyroid imaging or during surgery. Here, we present an extremely rare case of an occult FTC with overt skeletal metastases in which primary tumor was discernible only on microscopic examination.
Xenobiotica; the fate of foreign compounds in biological systems, Jan 22, 2018
1) 16α-hydroxycleroda-3, 13(14) Z -dien-15, 16-olide (4655K-09 or K-09) is a novel clerodane dite... more 1) 16α-hydroxycleroda-3, 13(14) Z -dien-15, 16-olide (4655K-09 or K-09) is a novel clerodane diterpene lactone reported for its anti hyperlipidemic efficacy. The objective of the present study was to investigate the probable reversible metabolism of 4655K-09 and evaluate its effects on pharmacokinetic (PK) properties. 2) The PK studies were carried out through intravenous (IV) bolus administration of 4655K-09 and K-9T in mice at a dose of 3, 6, and 12 mg/kg separately. The oral PK study of 4655K-09 were carried out at therapeutic dose of 25 mg/kg. 3) The % AUC of metabolite converted to parent upon its administration [Formula: see text] was found to be 27.28 ± 2.67. The multi-compartmental interconversion model defined reversible and irreversible clearances along with volumes of distribution for parent and metabolite. The results emphasized that hydrolysis of lactone to acid was more efficient than back conversion to parent due to greater extent of irreversible elimination of acid. ...
Most of the cases of PHPT in developing countries present in symptomatic stage, some even in very... more Most of the cases of PHPT in developing countries present in symptomatic stage, some even in very advanced stage but in recent years the trend seems to be changing. This has been corroborated from few recently published literature from developing countries. The scope of this study is to further carry out an in-depth analysis of various clinical and biochemical parameters of PHPT patients at a tertiary care center of northern India. In this retrospective analysis, a total of 333 patients with PHPT from the year 1990 to 2016 were studied. The study population was divided into three subgroups based on the time span; 1990-1999 (n = 34), 2000-2009 (n = 112), 2010-2016 (n = 187), and clinical and biochemical parameters were compared. The clinical presentation has evolved progressively with increase in older age group (35 vs 39 vs 43.85, p < 0.001), less patients with musculoskeletal symptoms (85.3 vs 76.8 vs 61%, p = 0.002) and less patients with severe bone disease (29.4 vs 10.7 vs 10...
The current standard-of-care for surgical staging of the axilla in clinically node-negative (N0) ... more The current standard-of-care for surgical staging of the axilla in clinically node-negative (N0) early breast cancers is sentinel lymph node biopsy (SLNB), which requires expensive radiopharmaceuticals for efficacious results. In-house produced low-cost radiopharmaceuticals may be the solution and have shown efficacy in earlier observational/pilot studies. We compared SLNB using in-house prepared radiopharmaceutical (Tc-Antimony-colloid) versus commercially marketed radiopharmaceutical (Tc-Sulphur-colloid) in this prospective randomized study. 78 clinically N0 early breast cancer patients (T1/2, N0 stages), undergoing primary surgery were prospectively randomized 1:1 into two groups; to receive SLNB using methylene blue, and eitherTc-Antimony colloid (Group-1) or Tc-Sulphur colloid (Group-2). Completion axillary dissection was done in all (validation SLNB). SLNB indices were compared between the groups. The groups were comparable with regard to age, stage, tumour size, hormone rece...
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