Vickram Tandon - Academia.edu (original) (raw)

Papers by Vickram Tandon

Plastic and reconstructive surgery, 2016

Plastic surgeons are frequently consulted for hand and facial injuries, and patients are often tr... more Plastic surgeons are frequently consulted for hand and facial injuries, and patients are often transferred to trauma centers for evaluation of these problems. The authors sought to identify the frequency and impact of "unnecessary" transfers for emergency evaluation by a plastic surgeon at a Level I trauma center. The authors reviewed more than 32,000 consecutive emergency department encounters at their institution between April of 2009 and April of 2013 and found 1181 patients transferred for evaluation by plastic surgery. Using a retrospective chart review, necessity of transfer was determined based on the intervention performed at the authors' institution and the availability of resources at the transferring site. Of all the patients referred for "emergency" evaluation, 860 (74.1 percent) were unnecessary. Transfers for hand-related issues were more likely to be coded as unnecessary compared with referrals for facial trauma and infection (76 percent versus...

Plos One, 2011

Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to ben... more Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease.

Plastic and reconstructive surgery, 2015

PLoS ONE, 2013

Tumor associated macrophages (TAMs) are recruited from the circulation to the tumor site, and can... more Tumor associated macrophages (TAMs) are recruited from the circulation to the tumor site, and can undergo a spectrum of phenotypic changes, with two contrasting activation states described in the literature: the M1 and M2 phenotypes. We previously identified a population of TAMs that express proliferating cell nuclear antigen (PCNA) and are associated with high grade, hormone receptor negative breast cancers and poor outcomes. In the present exploratory study we again found that high PCNA + TAM counts in pre-treatment tumor biopsies (102 invasive breast cancer cases from the I-SPY 1 Trial, a prospective neoadjuvant trial with serial core biopsies and gene array data) were associated with high grade, hormone receptor negativity, and decreased recurrence free survival. We explored the association of these PCNA + TAMs with the expression of M1 and M2 related genes and, contrary to expectation, observed that high PCNA + TAM levels were associated with more M1-than M2-related genes. An immune gene signature, derived from cytotoxic T cell and MHC Class II genes (Tc/ClassII), was developed and we found that high PCNA + TAM counts, in the context of a low Tc/ClassII signature score, were associated with significantly worse recurrence free survival in all cases and in hormone receptor negative only cases. We observed similar results using a gene signature-proxy for PCNA + TAMs in a larger independent set of 425 neoadjuvant-treated breast cancer cases. The results of this exploratory study indicate that high numbers of PCNA + TAMs, in the absence of an anti-tumor immune microenvironment (as indicated by a low Tc/ClassII signature score), are associated with poor outcomes in breast cancer patients treated with neoadjuvant chemotherapy. This, along with the observation that PCNA + TAMs were associated predominantly with M1-related genes, may provide new insights into the role of the immune microenvironment in breast cancer.

Plastic and reconstructive surgery, 2014

ABSTRACT Introduction: Hand and facial injuries represent greater than one quarter of all traumat... more ABSTRACT Introduction: Hand and facial injuries represent greater than one quarter of all traumatic injuries presenting to emergency departments (EDs) in the United States each year. Plastic surgeons are frequently consulted for these injuries, and patients are often transferred to trauma centers for evaluation by a specialist. We sought to identify the frequency and impact of “unnecessary” transfers for emergency evaluation by a plastic surgeon at Rhode Island’s only Level I trauma center. Methods: We reviewed more than 30,000 consecutive ED referrals to our institution. Of 1256 transferred for hand or facial emergencies, 76 were excluded from because they had poly-trauma or requested a specialty consultation not primarily by a plastic surgeon. Using a retrospective chart review, each referral was coded as either appropriate or inappropriate based both on the intervention performed at our institution and the availability of these resources at the transferring site. Results: A total of 1180 patients were transferred for “specialist” evaluation of hand or facial emergency. The mean age was 36 years old and the majority were males (71%). Most were transferred from another ED (73%). Of all the patients referred for ‘emergency’ evaluation, 321 (27.1%) were necessary. Transfers for hand trauma were more likely to be coded as unnecessary more often than for facial traumas (76% vs. 66%, p < 0.001). The average time from referral to discharge from the ED was 592 minutes, including transit time and ED evaluation time. From available hospital charges, the expense for these unnecessary transfers exceeded 3 million. Conclusions: This is the first intervention-based study evaluating the frequency and impact of unnecessary transfer for evaluation of hand and facial “emergencies.” Using a classification system based on EMTALA regulations, we found that less than one third of patients required emergent transfer. Over half of patients who were transferred did not receive an intervention from a plastic surgeon. Based on patient time and financial expenses for these unnecessary evaluations, significant improvements could be made in both quality and cost of care by limiting inappropriate ED referrals. There already exists a framework for patient transfer from the community ED to tertiary care center according to the American College of Surgeon Advance Trauma Life Support guideline. We present similar guidelines for patients who need emergent face and hand consultation.

Toxicology Letters, 2009

S93 group were noted in the lipid soluble liver extract. Furthermore, alterations in the levels o... more S93 group were noted in the lipid soluble liver extract. Furthermore, alterations in the levels of lipoproteins, alanine, glutamine, glutamate, and glucose were noted in serum. The above-mentioned metabolic alterations have an impact on both metabolically relative systems affected by liver injury and neurotransmission Moreover, PCA of liver tissue extracts and serum samples revealed a distinct separation between experimental and control animals.

PLoS ONE, 2011

Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to ben... more Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease.

Plastic and Reconstructive Surgery, 2014

Breast Cancer Research and Treatment, 2011

Breast cancer has a long natural history. Established and emerging biologic markers address overa... more Breast cancer has a long natural history. Established and emerging biologic markers address overall risk but not necessarily timing of recurrence. 346 adjuvant naïve breast cancer cases from Guy's Hospital with 23 years minimum follow-up and archival blocks were recut and reassessed for hormone-receptors (HR), HER2-receptor and grade. Disease-specific survival (DSS) was analyzed by recursive partitioning. To validate insights from this analysis, gene-signatures (proliferative and HR-negative) were evaluated for their ability to predict early versus late metastatic risk in 683 node-negative, adjuvant naïve breast cancers annotated with expression microarray data. Risk partitioning showed that adjuvant naïve node-negative outcome risk was primarily partitioned by tumor receptor status and grade but not tumor size. HR-positive and HER2-negative (HRpos) risk was partitioned by tumor grade; low grade cases have very low early risk but a 20% fall-off in DSS 10 or more years after diagnosis. Higher grade HRpos cases have risk over >20 years. Triple-negative (Tneg) and HER2-positive (HER2pos) cases DSS events occurred primarily within the first 5 years. Among node-positive cases, only low grade conferred late risk, suggesting that proliferative gene signatures that identify proliferation would be important for predicting early but not late recurrence. Using pooled data from four publicly available data sets for node-negative tumors annotated with gene expression and outcome data, we evaluated four prognostic gene signatures: two proliferation-based and two immune function-based. Tumor proliferative capacity predicted early but not late metastatic risk for HRpos cases. The immune function or HRneg specific signatures predicted only early metastatic risk in Tneg and HER2pos cases. Breast cancer prognostic signatures need to inform both risk and timing of metastatic events and may best be applied within subsets. Current signatures predict for outcome risk within 5 years of diagnosis. Predictors of late risk for HR positive disease are needed.

Annals of Surgical Oncology, 2013

Purpose. This study was designed to determine (1) rates of clinically meaningful tumor reduction ... more Purpose. This study was designed to determine (1) rates of clinically meaningful tumor reduction in breast tumor size following neoadjuvant chemotherapy (NAC), (2) which receptor subtypes and MRI phenotypes are associated with clinically meaningful tumor reduction, and (3) whether MRI phenotype impacts concordance between pathologic and MRI size. Methods. We analyzed data from the I-SPY TRIAL, a multicenter, prospective NAC trial. Reduction in tumor size from [4 to B4 cm was considered clinically meaningful, as crossing this threshold was considered a reasonable cutoff for potential breast conservation therapy (BCT). MRI phenotypes were scored between one (welldefined) and five (diffuse) on pre-NAC MRIs. Results. Of 174 patients with tumors [4 cm, 141 (81 %) had clinically meaningful tumor reduction. Response to therapy varied by MRI phenotype (p = 0.003), with welldefined phenotypes more likely than diffuse phenotypes to have clinically meaningful tumor shrinkage (91 vs. 72 %, p = 0.037). Her2? and triple-negative (Tneg) tumors had the highest rate of clinically meaningful tumor reduction (p = 0.005). The concordance between tumor diameter on Nola Hylton, Laura J. Esserman-Co-last authors.

Annals of Surgical Oncology, 2012

Purpose. Macrophages play a major role in inflammatory processes and have been associated with po... more Purpose. Macrophages play a major role in inflammatory processes and have been associated with poor prognosis in a variety of cancers, including breast cancer. Previously, we investigated the relationship of a subset of tumorassociated macrophages (PCNA ? TAMs) with clinicopathologic characteristics of breast cancer. We reported that high PCNA ? TAM counts were associated with hormone receptor (HR)-negative, high-grade tumors and early recurrence. To further understand the significance of elevated PCNA ? TAMs and the functionality of TAMs, we examined the expression of S100A8/S100A9 with the antibody Mac387. The heterodimeric S100A8/S100A9 complex plays a role in inflammation and is increased in several cancer types. Methods. We performed immunohistochemistry using the Mac387 antibody on 367 invasive human breast cancer cases. Results were compared to previous PCNA ? TAM

Plastic and Reconstructive Surgery, 2015

Plastic and reconstructive surgery, 2016

Plastic surgeons are frequently consulted for hand and facial injuries, and patients are often tr... more Plastic surgeons are frequently consulted for hand and facial injuries, and patients are often transferred to trauma centers for evaluation of these problems. The authors sought to identify the frequency and impact of "unnecessary" transfers for emergency evaluation by a plastic surgeon at a Level I trauma center. The authors reviewed more than 32,000 consecutive emergency department encounters at their institution between April of 2009 and April of 2013 and found 1181 patients transferred for evaluation by plastic surgery. Using a retrospective chart review, necessity of transfer was determined based on the intervention performed at the authors' institution and the availability of resources at the transferring site. Of all the patients referred for "emergency" evaluation, 860 (74.1 percent) were unnecessary. Transfers for hand-related issues were more likely to be coded as unnecessary compared with referrals for facial trauma and infection (76 percent versus...

Plos One, 2011

Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to ben... more Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease.

Plastic and reconstructive surgery, 2015

PLoS ONE, 2013

Tumor associated macrophages (TAMs) are recruited from the circulation to the tumor site, and can... more Tumor associated macrophages (TAMs) are recruited from the circulation to the tumor site, and can undergo a spectrum of phenotypic changes, with two contrasting activation states described in the literature: the M1 and M2 phenotypes. We previously identified a population of TAMs that express proliferating cell nuclear antigen (PCNA) and are associated with high grade, hormone receptor negative breast cancers and poor outcomes. In the present exploratory study we again found that high PCNA + TAM counts in pre-treatment tumor biopsies (102 invasive breast cancer cases from the I-SPY 1 Trial, a prospective neoadjuvant trial with serial core biopsies and gene array data) were associated with high grade, hormone receptor negativity, and decreased recurrence free survival. We explored the association of these PCNA + TAMs with the expression of M1 and M2 related genes and, contrary to expectation, observed that high PCNA + TAM levels were associated with more M1-than M2-related genes. An immune gene signature, derived from cytotoxic T cell and MHC Class II genes (Tc/ClassII), was developed and we found that high PCNA + TAM counts, in the context of a low Tc/ClassII signature score, were associated with significantly worse recurrence free survival in all cases and in hormone receptor negative only cases. We observed similar results using a gene signature-proxy for PCNA + TAMs in a larger independent set of 425 neoadjuvant-treated breast cancer cases. The results of this exploratory study indicate that high numbers of PCNA + TAMs, in the absence of an anti-tumor immune microenvironment (as indicated by a low Tc/ClassII signature score), are associated with poor outcomes in breast cancer patients treated with neoadjuvant chemotherapy. This, along with the observation that PCNA + TAMs were associated predominantly with M1-related genes, may provide new insights into the role of the immune microenvironment in breast cancer.

Plastic and reconstructive surgery, 2014

ABSTRACT Introduction: Hand and facial injuries represent greater than one quarter of all traumat... more ABSTRACT Introduction: Hand and facial injuries represent greater than one quarter of all traumatic injuries presenting to emergency departments (EDs) in the United States each year. Plastic surgeons are frequently consulted for these injuries, and patients are often transferred to trauma centers for evaluation by a specialist. We sought to identify the frequency and impact of “unnecessary” transfers for emergency evaluation by a plastic surgeon at Rhode Island’s only Level I trauma center. Methods: We reviewed more than 30,000 consecutive ED referrals to our institution. Of 1256 transferred for hand or facial emergencies, 76 were excluded from because they had poly-trauma or requested a specialty consultation not primarily by a plastic surgeon. Using a retrospective chart review, each referral was coded as either appropriate or inappropriate based both on the intervention performed at our institution and the availability of these resources at the transferring site. Results: A total of 1180 patients were transferred for “specialist” evaluation of hand or facial emergency. The mean age was 36 years old and the majority were males (71%). Most were transferred from another ED (73%). Of all the patients referred for ‘emergency’ evaluation, 321 (27.1%) were necessary. Transfers for hand trauma were more likely to be coded as unnecessary more often than for facial traumas (76% vs. 66%, p < 0.001). The average time from referral to discharge from the ED was 592 minutes, including transit time and ED evaluation time. From available hospital charges, the expense for these unnecessary transfers exceeded 3 million. Conclusions: This is the first intervention-based study evaluating the frequency and impact of unnecessary transfer for evaluation of hand and facial “emergencies.” Using a classification system based on EMTALA regulations, we found that less than one third of patients required emergent transfer. Over half of patients who were transferred did not receive an intervention from a plastic surgeon. Based on patient time and financial expenses for these unnecessary evaluations, significant improvements could be made in both quality and cost of care by limiting inappropriate ED referrals. There already exists a framework for patient transfer from the community ED to tertiary care center according to the American College of Surgeon Advance Trauma Life Support guideline. We present similar guidelines for patients who need emergent face and hand consultation.

Toxicology Letters, 2009

S93 group were noted in the lipid soluble liver extract. Furthermore, alterations in the levels o... more S93 group were noted in the lipid soluble liver extract. Furthermore, alterations in the levels of lipoproteins, alanine, glutamine, glutamate, and glucose were noted in serum. The above-mentioned metabolic alterations have an impact on both metabolically relative systems affected by liver injury and neurotransmission Moreover, PCA of liver tissue extracts and serum samples revealed a distinct separation between experimental and control animals.

PLoS ONE, 2011

Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to ben... more Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease.

Plastic and Reconstructive Surgery, 2014

Breast Cancer Research and Treatment, 2011

Breast cancer has a long natural history. Established and emerging biologic markers address overa... more Breast cancer has a long natural history. Established and emerging biologic markers address overall risk but not necessarily timing of recurrence. 346 adjuvant naïve breast cancer cases from Guy's Hospital with 23 years minimum follow-up and archival blocks were recut and reassessed for hormone-receptors (HR), HER2-receptor and grade. Disease-specific survival (DSS) was analyzed by recursive partitioning. To validate insights from this analysis, gene-signatures (proliferative and HR-negative) were evaluated for their ability to predict early versus late metastatic risk in 683 node-negative, adjuvant naïve breast cancers annotated with expression microarray data. Risk partitioning showed that adjuvant naïve node-negative outcome risk was primarily partitioned by tumor receptor status and grade but not tumor size. HR-positive and HER2-negative (HRpos) risk was partitioned by tumor grade; low grade cases have very low early risk but a 20% fall-off in DSS 10 or more years after diagnosis. Higher grade HRpos cases have risk over >20 years. Triple-negative (Tneg) and HER2-positive (HER2pos) cases DSS events occurred primarily within the first 5 years. Among node-positive cases, only low grade conferred late risk, suggesting that proliferative gene signatures that identify proliferation would be important for predicting early but not late recurrence. Using pooled data from four publicly available data sets for node-negative tumors annotated with gene expression and outcome data, we evaluated four prognostic gene signatures: two proliferation-based and two immune function-based. Tumor proliferative capacity predicted early but not late metastatic risk for HRpos cases. The immune function or HRneg specific signatures predicted only early metastatic risk in Tneg and HER2pos cases. Breast cancer prognostic signatures need to inform both risk and timing of metastatic events and may best be applied within subsets. Current signatures predict for outcome risk within 5 years of diagnosis. Predictors of late risk for HR positive disease are needed.

Annals of Surgical Oncology, 2013

Purpose. This study was designed to determine (1) rates of clinically meaningful tumor reduction ... more Purpose. This study was designed to determine (1) rates of clinically meaningful tumor reduction in breast tumor size following neoadjuvant chemotherapy (NAC), (2) which receptor subtypes and MRI phenotypes are associated with clinically meaningful tumor reduction, and (3) whether MRI phenotype impacts concordance between pathologic and MRI size. Methods. We analyzed data from the I-SPY TRIAL, a multicenter, prospective NAC trial. Reduction in tumor size from [4 to B4 cm was considered clinically meaningful, as crossing this threshold was considered a reasonable cutoff for potential breast conservation therapy (BCT). MRI phenotypes were scored between one (welldefined) and five (diffuse) on pre-NAC MRIs. Results. Of 174 patients with tumors [4 cm, 141 (81 %) had clinically meaningful tumor reduction. Response to therapy varied by MRI phenotype (p = 0.003), with welldefined phenotypes more likely than diffuse phenotypes to have clinically meaningful tumor shrinkage (91 vs. 72 %, p = 0.037). Her2? and triple-negative (Tneg) tumors had the highest rate of clinically meaningful tumor reduction (p = 0.005). The concordance between tumor diameter on Nola Hylton, Laura J. Esserman-Co-last authors.

Annals of Surgical Oncology, 2012

Purpose. Macrophages play a major role in inflammatory processes and have been associated with po... more Purpose. Macrophages play a major role in inflammatory processes and have been associated with poor prognosis in a variety of cancers, including breast cancer. Previously, we investigated the relationship of a subset of tumorassociated macrophages (PCNA ? TAMs) with clinicopathologic characteristics of breast cancer. We reported that high PCNA ? TAM counts were associated with hormone receptor (HR)-negative, high-grade tumors and early recurrence. To further understand the significance of elevated PCNA ? TAMs and the functionality of TAMs, we examined the expression of S100A8/S100A9 with the antibody Mac387. The heterodimeric S100A8/S100A9 complex plays a role in inflammation and is increased in several cancer types. Methods. We performed immunohistochemistry using the Mac387 antibody on 367 invasive human breast cancer cases. Results were compared to previous PCNA ? TAM

Plastic and Reconstructive Surgery, 2015