Ankur Seth - Academia.edu (original) (raw)

Papers by Ankur Seth

World Journal of Hematology

The primary aim of World Journal of Hematology (WJH, World J Hematol) is to provide scholars and ... more The primary aim of World Journal of Hematology (WJH, World J Hematol) is to provide scholars and readers from various fields of hematology with a platform to publish high-quality basic and clinical research articles and communicate their research findings online. WJH mainly publishes articles reporting research results and findings obtained in the field of hematology and covering a wide range of topics including anemia, blood coagulation disorders, blood group incompatibility, blood platelet disorders, blood protein disorders, bone marrow diseases, hematologic neoplasms, hemoglobinopathies, hemorrhagic disorders, leukocyte disorders, methemoglobinemia, pancytopenia, polycythemia, hematologic pregnancy complications, preleukemia, sulfhemoglobinemia, and thrombophilia.

World Journal of Hematology

The primary aim of World Journal of Hematology (WJH, World J Hematol) is to provide scholars and ... more The primary aim of World Journal of Hematology (WJH, World J Hematol) is to provide scholars and readers from various fields of hematology with a platform to publish high-quality basic and clinical research articles and communicate their research findings online. WJH mainly publishes articles reporting research results and findings obtained in the field of hematology and covering a wide range of topics including anemia, blood coagulation disorders, blood group incompatibility, blood platelet disorders, blood protein disorders, bone marrow diseases, hematologic neoplasms, hemoglobinopathies, hemorrhagic disorders, leukocyte disorders, methemoglobinemia, pancytopenia, polycythemia, hematologic pregnancy complications, preleukemia, sulfhemoglobinemia, and thrombophilia.

Ophthalmology Journal, 2021

This article is available in open access under Creative Common Attribution-Non-Commercial-No Deri... more This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially

Ophthalmology Journal, 2021

This article is available in open access under Creative Common Attribution-Non-Commercial-No Deri... more This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially

Journal of the National Medical Association, 2020

BACKGROUND The Center for Medicare and Medicaid Services (CMS) has targeted hospital readmissions... more BACKGROUND The Center for Medicare and Medicaid Services (CMS) has targeted hospital readmissions, which cost $17 billion per year, as one potential solution to reduce rising health care costs. Studies have documented the ability of Transitions of care (TOC) services to reduce readmissions in high risk patients. However, the vast majority of studies have not explored TOC services for all-cause admissions nor TOC clinics led by hospitalists. The goal of this study is to provide preliminary data regarding the potential effectiveness of a hospitalist-led TOC clinic servicing all patients on hospital readmission rates. METHODS This cross-sectional feasibility study analyzed patients on a tertiary hospital teaching service. All discharged patients from January 2016 to September 2018 were given an appointment at the TOC clinic within 14 days of discharge. The control group consisted of patients assigned to the teaching service from January 2018 to November 2018 that were not offered a TOC appointment. RESULTS Overall, 1373 patients (n = 1373) were included in this study between January 2016 and September 2018. The control group consisted of 1000 patients who were not offered follow up in the TOC clinic while the TOC group consisted of 373 patients who did attend a follow up appointment in the TOC clinic. The study participants (n = 1373) included patients admitted to the hospital for any diagnosis and were analyzed for all cause readmission rates. The TOC group consisted of 52% African Americans, 52% Medicare patients and 8% Medicaid patients. Demographic information for the control group was not available. The TOC group had a statistically significant 42% decreased risk of being readmitted within 30 days of discharge (RR = 0.58, 95% CI: 0.40-0.83). These data showed a statistically significant difference between the TOC group and control group in relation to the incidence of 30-day readmissions (p-value = 0.002). CONCLUSION Among Medicare and Medicaid beneficiaries and commercial health insurance patients, this hospitalist-led TOC intervention was associated with a statistically significant reduction in 30-day readmissions following discharge for all-cause hospital admissions.

Journal of the National Medical Association, 2020

BACKGROUND The Center for Medicare and Medicaid Services (CMS) has targeted hospital readmissions... more BACKGROUND The Center for Medicare and Medicaid Services (CMS) has targeted hospital readmissions, which cost $17 billion per year, as one potential solution to reduce rising health care costs. Studies have documented the ability of Transitions of care (TOC) services to reduce readmissions in high risk patients. However, the vast majority of studies have not explored TOC services for all-cause admissions nor TOC clinics led by hospitalists. The goal of this study is to provide preliminary data regarding the potential effectiveness of a hospitalist-led TOC clinic servicing all patients on hospital readmission rates. METHODS This cross-sectional feasibility study analyzed patients on a tertiary hospital teaching service. All discharged patients from January 2016 to September 2018 were given an appointment at the TOC clinic within 14 days of discharge. The control group consisted of patients assigned to the teaching service from January 2018 to November 2018 that were not offered a TOC appointment. RESULTS Overall, 1373 patients (n = 1373) were included in this study between January 2016 and September 2018. The control group consisted of 1000 patients who were not offered follow up in the TOC clinic while the TOC group consisted of 373 patients who did attend a follow up appointment in the TOC clinic. The study participants (n = 1373) included patients admitted to the hospital for any diagnosis and were analyzed for all cause readmission rates. The TOC group consisted of 52% African Americans, 52% Medicare patients and 8% Medicaid patients. Demographic information for the control group was not available. The TOC group had a statistically significant 42% decreased risk of being readmitted within 30 days of discharge (RR = 0.58, 95% CI: 0.40-0.83). These data showed a statistically significant difference between the TOC group and control group in relation to the incidence of 30-day readmissions (p-value = 0.002). CONCLUSION Among Medicare and Medicaid beneficiaries and commercial health insurance patients, this hospitalist-led TOC intervention was associated with a statistically significant reduction in 30-day readmissions following discharge for all-cause hospital admissions.

Chest, 2018

To address the relationship between age and the efficacy and safety of the direct oral anticoagul... more To address the relationship between age and the efficacy and safety of the direct oral anticoagulants (DOACs), we performed a systematic review and meta-analysis to evaluate the incidence of recurrent venous thromboembolism (VTE) in nonelderly (less than or equal to 65 years) versus elderly patients (greater than 65 years) with acute VTE treated with DOACs compared to vitamin K antagonists (VKAs). Previous meta-analyses evaluated this using age cutoffs of greater than or less than 75 years, with the former group making up a small portion of the study population in the respective DOAC trials. METHODS: We searched several databases from inception until 1 November 2017 for comparative studies evaluating the use of DOACs in preventing recurrent VTE in elderly versus non-elderly patients.. Search terms included 'novel oral anticoagulant', 'vitamin K antagonist', 'warfarin', and/or venous thromboembolism. The outcome of interest was recurrent VTE. Pooled risk ratios (RR) were pooled and analyzed using a random effects model. RESULTS: Eight studies including 26,350 patients were included in this analysis. For incidence of recurrent VTE in the study population, pooled RR was 0.87 (0.60-1.24). For recurrent VTE in non-elderly patients, pooled RR was 0.52 (0.27-0.99). Significant heterogeneity of 91% was noted for this outcome. For recurrent VTE in elderly patients, pooled RR was 0.56 (0.33-0.94). Significant heterogeneity of 71% was noted for this outcome. The heterogeneity persisted for recurrent VTE in both elderly and non-elderly patients despite adjusting for specific DOAC used. CONCLUSIONS: Moderate-to-high quality evidence suggests DOAC use was associated with a statistically significant reduction in the incidence of recurrent VTE in elderly and non-elderly patients. Significant heterogeneity noted for the outcome of interest indicates the reduction in VTE could be due to chance. CLINICAL IMPLICATIONS: Further randomized trials with elderly and non-elderly patients are needed to determine if DOAC use in patients with VTE is truly non-inferior to warfarin in this important subgroup of patients.

Chest, 2018

To address the relationship between age and the efficacy and safety of the direct oral anticoagul... more To address the relationship between age and the efficacy and safety of the direct oral anticoagulants (DOACs), we performed a systematic review and meta-analysis to evaluate the incidence of recurrent venous thromboembolism (VTE) in nonelderly (less than or equal to 65 years) versus elderly patients (greater than 65 years) with acute VTE treated with DOACs compared to vitamin K antagonists (VKAs). Previous meta-analyses evaluated this using age cutoffs of greater than or less than 75 years, with the former group making up a small portion of the study population in the respective DOAC trials. METHODS: We searched several databases from inception until 1 November 2017 for comparative studies evaluating the use of DOACs in preventing recurrent VTE in elderly versus non-elderly patients.. Search terms included 'novel oral anticoagulant', 'vitamin K antagonist', 'warfarin', and/or venous thromboembolism. The outcome of interest was recurrent VTE. Pooled risk ratios (RR) were pooled and analyzed using a random effects model. RESULTS: Eight studies including 26,350 patients were included in this analysis. For incidence of recurrent VTE in the study population, pooled RR was 0.87 (0.60-1.24). For recurrent VTE in non-elderly patients, pooled RR was 0.52 (0.27-0.99). Significant heterogeneity of 91% was noted for this outcome. For recurrent VTE in elderly patients, pooled RR was 0.56 (0.33-0.94). Significant heterogeneity of 71% was noted for this outcome. The heterogeneity persisted for recurrent VTE in both elderly and non-elderly patients despite adjusting for specific DOAC used. CONCLUSIONS: Moderate-to-high quality evidence suggests DOAC use was associated with a statistically significant reduction in the incidence of recurrent VTE in elderly and non-elderly patients. Significant heterogeneity noted for the outcome of interest indicates the reduction in VTE could be due to chance. CLINICAL IMPLICATIONS: Further randomized trials with elderly and non-elderly patients are needed to determine if DOAC use in patients with VTE is truly non-inferior to warfarin in this important subgroup of patients.

Chest, 2018

To evaluate if sex influences the efficacy and safety of direct oral anticoagulant use for extend... more To evaluate if sex influences the efficacy and safety of direct oral anticoagulant use for extended thromboprophylaxis (ET) against venous thromboembolism (VTE) in acutely ill medical patients METHODS: We searched several databases from inception to 31 December 2017 to identify comparative studies evaluating direct oral anticoagulants for ET against VTE in acutely ill medical patients. Only randomized controlled trials were included in this systematic review and meta-analysis. Outcomes of interest were total VTE events and major bleeding. Adjusted odds ratios (OR) were pooled and analyzed using a random effects model. RESULTS: We included 3 randomized controlled trials with 17,305 patients (8,659 males and 8,646 females). For total VTE events in males, pooled OR (95% confidence interval) was 0.79 (0.65-0.96). For total VTE events in females, pooled OR (95% confidence interval) was 0.63 (0.44-0.90). For major bleeding in males, pooled OR (95% confidence interval) was 1.34 (0.51-3.51). For major bleeding in females, pooled OR (95% confidence interval) was 2.74 (1.90-3.96). CONCLUSIONS: Sex-related differences do exist for the efficacy and safety of direct oral anticoagulant for extended thromboprophylaxis in acutely ill medical patients. Female and male patients have a lower risk for VTE events with direct oral anticoagulant use for extended thromboprophylaxis. While females have fewer VTE events with ET compared to males, the clinically and statistically significant increased for major bleeding obviates this benefit. CLINICAL IMPLICATIONS: Extended thromboprophylaxis in acutely ill medical patients remains a topic of great debate. Our current meta-analysis highlights the ongoing need to determine subgroups of patients that benefit from use of direct oral anticoagulants for extended thromboprophylaxis without increasing the risk for bleeding.

Southern Medical Journal, 2019

Acknowledgements Foreword Principal recommendations Introduction Chapter 1-Method and data return... more Acknowledgements Foreword Principal recommendations Introduction Chapter 1-Method and data returns Chapter 2-Organisational data Key Findings Chapter 3-Prospective data 3.1 Total population data 3.2 Outcome data 3.3 Risk 3.4 The surgery undertaken Key Findings Recommendations Chapter 4-Peer review case data 4.1 Descriptive data 4.2 Outcome of peer review cases 4.3 Overall assessment of care 4.4 Risk assessment 4.5 Pre-operative assessment 4.6 Consent 4.7 Pre-operative phase 4.8 Intra-operative phase 4.9 Postoperative phase Key Findings Recommendations Summary References Appendix 1-Glossary Appendix 2-Six month outcome data Appendix 3-Role and structure of NCEPOD Appendix 4-Hospital participation This report, published by NCEPOD, could not have been achieved without the support of a wide range of individuals who have contributed to this study. Our particular thanks go to:

Gastroenterology, 2017

Background: Hepatic encephalopathy (HE) is a leading cause of readmission due to recurrence despi... more Background: Hepatic encephalopathy (HE) is a leading cause of readmission due to recurrence despite standard of care (SOC, lactulose+rifaximin). These pts also receive multiple antibiotic courses & develop lasting cognitive injury. Fecal microbiota transplantation (FMT) is a promising approach but there is a paucity of data. Aim: To define the safety profile, impact on liver and cognition of FMT for recurrent HE using a rationally-derived stool donor. Methods: Using cross-sectional HE microbiome data, the ideal OpenBiome donor for HE pts (with highest autochthonous taxa) was identified using Random Forrest analysis. Recurrent HE outpts on SOC were randomized to FMT or SOC under an FDA IND. The FMT arm received 5-days of broad-spectrum antibiotics then a single FMT enema(90ml) from the same donor. Follow-up occurred Day 5,6,12,35 & 150, post-randomization. Outcomes included safety, cognition, microbiome & urinary metabolomics. Results: 20 cirrhotic men (all on lactulose, rifaximin & PPI, last HE 4 mths ago) were randomized 1:1 to FMT or SOC. Both arms (FMT vs SOC) were similar in age(64 vs 63), MELD(12.3 vs 13), albumin(3.2 vs 3.1) & alcoholic etiology (6 vs 7). Hospitalizations: Overall, 10 hospitalizations (median 100, IQR 83 days) occurred in the SOC arm (4 HE, 2 variceal bleeding, 2 chest pain,1 diarrhea,1 anemia) compared to 1 FMT (83 days FMT-unrelated, p=0.001). FMT arm: Antibiotics & FMT were well tolerated without related serious adverse events. There was a significant cognitive improvement on PHES & Stroop App in FMT but not in the SOC arm compared to baseline (Figure). MELD significantly increased postantibiotics (delta 1.7,p<0.001), but reverted to baseline post-FMT (delta-0.2,p=0.5 day 20). Microbiome analysis showed antibiotic-related autochthonous taxa reduction and Proteobacteria expansion. FMT increased beneficial taxa (Bifidobacteriaceae, Lactobacillaceae).This accompanied a favorable changes in urine metabolomics with reduced microbial products (hippurate & phenylacetylglycine). One pt worsened cognitively; however, they had higher baseline Proteobacteria, which did not respond to FMT & was subsequently hospitalized. SOC arm: No significant microbiota, metabolomic, cognitive or MELD changes were seen in SOC arm. Conclusions: In the first randomized trial, FMT using a single donor identified through a Precision Medicine approach appears to be safe, reduces hospitalizations, improves cognitive function and restores antibiotic-associated microbial changes in recurrent HE Tu1549

Cureus, 2017

Adrenal masses pose a diagnostic challenge. The differential diagnosis includes functional adrena... more Adrenal masses pose a diagnostic challenge. The differential diagnosis includes functional adrenal tumors, incidentally found adrenal masses, metastases from an unknown primary cancer, and abscesses. Infrequently, adrenal gland abscesses have been reported in disseminated nocardiosis affecting immunocompetent and immunocompromised patients. We report a case of disseminated Nocardia farcinica pneumonia with an adrenal gland abscess in an immunocompetent patient with no identified risk factors for nocardiosis.

The American Journal of the Medical Sciences, 2017

bleeding source were 0.84 (0.46 to 1.53), 1.18 (0.64 to 2.16), and 1.49 (0.86 to 2.59), respectiv... more bleeding source were 0.84 (0.46 to 1.53), 1.18 (0.64 to 2.16), and 1.49 (0.86 to 2.59), respectively. Stigmata of recent hemorrhage were more readily identified with urgent colonoscopy OR 2.85 (1.90 to 4.28). There were no differences in requirement for surgery, length of hospital stay or rate of endoscopic intervention. However, these effect sizes were limited by considerable heterogeneity which was probably due to studies being conducted in different countries having different criteria for discharge and on variations in the type of endoscopic therapy for stigmata of recent hemorrhage. Conclusions Among patients with acute LGIB, there is no evidence that urgent colonoscopy reduces mortality, re-bleeding or requirement for surgery or that it improves the rate of identification of the bleeding source. However, urgent colonoscopy does increase the rate of detection of stigmata of recent hemorrhage.

Proceedings of the National Academy of Sciences, 2008

PKCη is expressed predominantly in the epithelial tissues; however, its role in the regulation of... more PKCη is expressed predominantly in the epithelial tissues; however, its role in the regulation of epithelial tight junctions (TJs) is unknown. We present evidence that PKCη phosphorylates occludin on threonine residues (T403 and T404) and plays a crucial role in the assembly and/or maintenance of TJs in Caco-2 and MDCK cell monolayers. Inhibition of PKCη by specific pseudo substrate inhibitor or knockdown of PKCη by specific shRNA disrupts the junctional distribution of occludin and ZO-1 and compromises the epithelial barrier function. Expression of dominant negative, PKCη K394R disrupts the TJ and barrier function, whereas wild-type PKCη and constitutively active PKCη A161E enhance the TJ integrity. Inhibition and knockdown of PKCη or expression of PKCη K394R induce dephosphorylation of occludin on threonine residues, whereas active PKCη elevates occludin phosphorylation. PKCη directly interacts with the C-terminal domain of occludin and phosphorylates it on highly conserved T403 a...

Laboratory Investigation, 2011

The tight junctions of bile duct epithelium form a barrier between the toxic bile and liver paren... more The tight junctions of bile duct epithelium form a barrier between the toxic bile and liver parenchyma. Disruption of tight junctions appears to have a crucial role in the pathogenesis of various liver diseases. In this study, we investigated the disruptive effect of hydrogen peroxide and the protective effect of epidermal growth factor (EGF) on the tight junctions and adherens junctions in the bile duct epithelium. Oxidative stress in NRC-1 and Mz-ChA-1 cell monolayers was induced by administration of hydrogen peroxide. Barrier function was evaluated by measuring electrical resistance and inulin permeability. Integrity of tight junctions, adherens junctions and the actin cytoskeleton was determined by imunofluorescence microscopy. Role of signaling molecules was determined by evaluating the effect of specific inhibitors. Hydrogen peroxide caused a rapid disruption of tight junctions and adherens junctions leading to barrier dysfunction without altering the cell viability. Hydrogen peroxide rapidly increased the levels of p-MLC (myosin light chain) and c-Src(pY418). ML-7 and PP2 (MLCK and Src kinase inhibitors) attenuated hydrogen peroxide-induced barrier dysfunction, tight junction disruption and reorganization of actin cytoskeleton. Pretreatment of cell monolayers with EGF ameliorated hydrogen peroxide-induced tight junction disruption and barrier dysfunction. The protective effect of EGF was abrogated by ET-18-OCH 3 and the Ro-32-0432 (PLCg and PKC inhibitors). Hydrogen peroxide increased tyrosine phosphorylation of ZO-1, claudin-3, E-cadherin and b-catenin, and pretreatment of cells with EGF attenuated tyrosine phosphorylation of these proteins. These results demonstrate that hydrogen peroxide disrupts tight junctions, adherens junctions and the actin cytoskeleton by an MLCK and Src kinase-dependent mechanism in the bile duct epithelium. EGF prevents hydrogen peroxide-induced tight junction disruption by a PLCg and PKC-dependent mechanism.

Journal of Biological Chemistry, 2008

Occludin is phosphorylated on tyrosine residues during the oxidative stress-induced disruption of... more Occludin is phosphorylated on tyrosine residues during the oxidative stress-induced disruption of tight junction, and in vitro phosphorylation of occludin by c-Src attenuates its binding to ZO-1. In the present study mass spectrometric analyses of C-terminal domain of occludin identified Tyr-379 and Tyr-383 in chicken occludin as the phosphorylation sites, which are located in a highly conserved sequence of occludin, YETDYTT; Tyr-398 and Tyr-402 are the corresponding residues in human occludin. Deletion of YETDYTT motif abolished the c-Src-mediated phosphorylation of occludin and the regulation of ZO-1 binding. Y398A and Y402A mutations in human occludin also abolished the c-Src-mediated phosphorylation and regulation of ZO-1 binding. Y398D/ Y402D mutation resulted in a dramatic reduction in ZO-1 binding even in the absence of c-Src. Similar to wild type occludin, its Y398A/Y402A mutant was localized at the plasma membrane and cell-cell contact sites in Rat-1 cells. However, Y398D/Y402D mutants of occludin failed to localize at the cell-cell contacts. Calcium-induced reassembly of Y398D/Y402D mutant occludin in Madin-Darby canine kidney cells was significantly delayed compared with that of wild type occludin or its T398A/T402A mutant. Furthermore, expression of Y398D/Y402D mutant of occludin sensitized MDCK cells for hydrogen peroxide-induced barrier disruption. This study reveals a unique motif in the occludin sequence that is involved in the regulation of ZO-1 binding by reversible phosphorylation of specific Tyr residues. Epithelial tight junctions (TJs) 2 form a selective barrier to the diffusion of toxins, allergens, and pathogens from the external environment into the tissues in the gastrointestinal tract, lung,

Journal of Biological Chemistry, 2007

Occludin is hyperphosphorylated on Ser and Thr residues in intact epithelial tight junction (TJ);... more Occludin is hyperphosphorylated on Ser and Thr residues in intact epithelial tight junction (TJ); however, the role of this phosphorylation in the assembly of TJ is unclear. The influence of protein phosphatases PP2A and PP1 on the assembly of TJ and phosphorylation of occludin was evaluated in Caco-2 cells. Protein phosphatase inhibitors and reduced expression of PP2A-C␣ and PP1␣ accelerated the calcium-induced increase in transepithelial electrical resistance and barrier to inulin permeability and also enhanced the junctional organization of occludin and ZO-1 during TJ assembly. Phosphorylation of occludin on Thr residues, but not on Ser residues, was dramatically reduced during the disassembly of TJ and was gradually increased during the reassembly. PP2A and PP1 co-immunoprecipitate with occludin, and this association was reduced during the assembly of TJ. Glutathione S-transferase (GST) pulldown assay using recombinant GST-occludin demonstrated that cellular PP2A and PP1 bind to the C-terminal tail of occludin, and these interactions were also reduced during the assembly of TJ. A pairwise binding assay using GST-occludin and purified PP2A and PP1 demonstrates that PP2A and PP1 directly interacts with the C-terminal tail of occludin. In vitro incubation of phospho-occludin with PP2A or PP1 indicated that PP2A dephosphorylates occludin on phospho-Thr residues, whereas PP1 dephosphorylates it on phospho-Ser. This study shows that PP2A and PP1 directly interact with occludin and negatively regulate the assembly of TJ by modulating the phosphorylation status of occludin.

Journal of Biological Chemistry, 2012

In the middle column of Fig. 6A, the wrong images were inserted. The corrected figure is shown be... more In the middle column of Fig. 6A, the wrong images were inserted. The corrected figure is shown below. This change does not alter the conclusion of the study.

World Journal of Hematology

The primary aim of World Journal of Hematology (WJH, World J Hematol) is to provide scholars and ... more The primary aim of World Journal of Hematology (WJH, World J Hematol) is to provide scholars and readers from various fields of hematology with a platform to publish high-quality basic and clinical research articles and communicate their research findings online. WJH mainly publishes articles reporting research results and findings obtained in the field of hematology and covering a wide range of topics including anemia, blood coagulation disorders, blood group incompatibility, blood platelet disorders, blood protein disorders, bone marrow diseases, hematologic neoplasms, hemoglobinopathies, hemorrhagic disorders, leukocyte disorders, methemoglobinemia, pancytopenia, polycythemia, hematologic pregnancy complications, preleukemia, sulfhemoglobinemia, and thrombophilia.

World Journal of Hematology

The primary aim of World Journal of Hematology (WJH, World J Hematol) is to provide scholars and ... more The primary aim of World Journal of Hematology (WJH, World J Hematol) is to provide scholars and readers from various fields of hematology with a platform to publish high-quality basic and clinical research articles and communicate their research findings online. WJH mainly publishes articles reporting research results and findings obtained in the field of hematology and covering a wide range of topics including anemia, blood coagulation disorders, blood group incompatibility, blood platelet disorders, blood protein disorders, bone marrow diseases, hematologic neoplasms, hemoglobinopathies, hemorrhagic disorders, leukocyte disorders, methemoglobinemia, pancytopenia, polycythemia, hematologic pregnancy complications, preleukemia, sulfhemoglobinemia, and thrombophilia.

Ophthalmology Journal, 2021

This article is available in open access under Creative Common Attribution-Non-Commercial-No Deri... more This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially

Ophthalmology Journal, 2021

This article is available in open access under Creative Common Attribution-Non-Commercial-No Deri... more This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially

Journal of the National Medical Association, 2020

BACKGROUND The Center for Medicare and Medicaid Services (CMS) has targeted hospital readmissions... more BACKGROUND The Center for Medicare and Medicaid Services (CMS) has targeted hospital readmissions, which cost $17 billion per year, as one potential solution to reduce rising health care costs. Studies have documented the ability of Transitions of care (TOC) services to reduce readmissions in high risk patients. However, the vast majority of studies have not explored TOC services for all-cause admissions nor TOC clinics led by hospitalists. The goal of this study is to provide preliminary data regarding the potential effectiveness of a hospitalist-led TOC clinic servicing all patients on hospital readmission rates. METHODS This cross-sectional feasibility study analyzed patients on a tertiary hospital teaching service. All discharged patients from January 2016 to September 2018 were given an appointment at the TOC clinic within 14 days of discharge. The control group consisted of patients assigned to the teaching service from January 2018 to November 2018 that were not offered a TOC appointment. RESULTS Overall, 1373 patients (n = 1373) were included in this study between January 2016 and September 2018. The control group consisted of 1000 patients who were not offered follow up in the TOC clinic while the TOC group consisted of 373 patients who did attend a follow up appointment in the TOC clinic. The study participants (n = 1373) included patients admitted to the hospital for any diagnosis and were analyzed for all cause readmission rates. The TOC group consisted of 52% African Americans, 52% Medicare patients and 8% Medicaid patients. Demographic information for the control group was not available. The TOC group had a statistically significant 42% decreased risk of being readmitted within 30 days of discharge (RR = 0.58, 95% CI: 0.40-0.83). These data showed a statistically significant difference between the TOC group and control group in relation to the incidence of 30-day readmissions (p-value = 0.002). CONCLUSION Among Medicare and Medicaid beneficiaries and commercial health insurance patients, this hospitalist-led TOC intervention was associated with a statistically significant reduction in 30-day readmissions following discharge for all-cause hospital admissions.

Journal of the National Medical Association, 2020

BACKGROUND The Center for Medicare and Medicaid Services (CMS) has targeted hospital readmissions... more BACKGROUND The Center for Medicare and Medicaid Services (CMS) has targeted hospital readmissions, which cost $17 billion per year, as one potential solution to reduce rising health care costs. Studies have documented the ability of Transitions of care (TOC) services to reduce readmissions in high risk patients. However, the vast majority of studies have not explored TOC services for all-cause admissions nor TOC clinics led by hospitalists. The goal of this study is to provide preliminary data regarding the potential effectiveness of a hospitalist-led TOC clinic servicing all patients on hospital readmission rates. METHODS This cross-sectional feasibility study analyzed patients on a tertiary hospital teaching service. All discharged patients from January 2016 to September 2018 were given an appointment at the TOC clinic within 14 days of discharge. The control group consisted of patients assigned to the teaching service from January 2018 to November 2018 that were not offered a TOC appointment. RESULTS Overall, 1373 patients (n = 1373) were included in this study between January 2016 and September 2018. The control group consisted of 1000 patients who were not offered follow up in the TOC clinic while the TOC group consisted of 373 patients who did attend a follow up appointment in the TOC clinic. The study participants (n = 1373) included patients admitted to the hospital for any diagnosis and were analyzed for all cause readmission rates. The TOC group consisted of 52% African Americans, 52% Medicare patients and 8% Medicaid patients. Demographic information for the control group was not available. The TOC group had a statistically significant 42% decreased risk of being readmitted within 30 days of discharge (RR = 0.58, 95% CI: 0.40-0.83). These data showed a statistically significant difference between the TOC group and control group in relation to the incidence of 30-day readmissions (p-value = 0.002). CONCLUSION Among Medicare and Medicaid beneficiaries and commercial health insurance patients, this hospitalist-led TOC intervention was associated with a statistically significant reduction in 30-day readmissions following discharge for all-cause hospital admissions.

Chest, 2018

To address the relationship between age and the efficacy and safety of the direct oral anticoagul... more To address the relationship between age and the efficacy and safety of the direct oral anticoagulants (DOACs), we performed a systematic review and meta-analysis to evaluate the incidence of recurrent venous thromboembolism (VTE) in nonelderly (less than or equal to 65 years) versus elderly patients (greater than 65 years) with acute VTE treated with DOACs compared to vitamin K antagonists (VKAs). Previous meta-analyses evaluated this using age cutoffs of greater than or less than 75 years, with the former group making up a small portion of the study population in the respective DOAC trials. METHODS: We searched several databases from inception until 1 November 2017 for comparative studies evaluating the use of DOACs in preventing recurrent VTE in elderly versus non-elderly patients.. Search terms included 'novel oral anticoagulant', 'vitamin K antagonist', 'warfarin', and/or venous thromboembolism. The outcome of interest was recurrent VTE. Pooled risk ratios (RR) were pooled and analyzed using a random effects model. RESULTS: Eight studies including 26,350 patients were included in this analysis. For incidence of recurrent VTE in the study population, pooled RR was 0.87 (0.60-1.24). For recurrent VTE in non-elderly patients, pooled RR was 0.52 (0.27-0.99). Significant heterogeneity of 91% was noted for this outcome. For recurrent VTE in elderly patients, pooled RR was 0.56 (0.33-0.94). Significant heterogeneity of 71% was noted for this outcome. The heterogeneity persisted for recurrent VTE in both elderly and non-elderly patients despite adjusting for specific DOAC used. CONCLUSIONS: Moderate-to-high quality evidence suggests DOAC use was associated with a statistically significant reduction in the incidence of recurrent VTE in elderly and non-elderly patients. Significant heterogeneity noted for the outcome of interest indicates the reduction in VTE could be due to chance. CLINICAL IMPLICATIONS: Further randomized trials with elderly and non-elderly patients are needed to determine if DOAC use in patients with VTE is truly non-inferior to warfarin in this important subgroup of patients.

Chest, 2018

To address the relationship between age and the efficacy and safety of the direct oral anticoagul... more To address the relationship between age and the efficacy and safety of the direct oral anticoagulants (DOACs), we performed a systematic review and meta-analysis to evaluate the incidence of recurrent venous thromboembolism (VTE) in nonelderly (less than or equal to 65 years) versus elderly patients (greater than 65 years) with acute VTE treated with DOACs compared to vitamin K antagonists (VKAs). Previous meta-analyses evaluated this using age cutoffs of greater than or less than 75 years, with the former group making up a small portion of the study population in the respective DOAC trials. METHODS: We searched several databases from inception until 1 November 2017 for comparative studies evaluating the use of DOACs in preventing recurrent VTE in elderly versus non-elderly patients.. Search terms included 'novel oral anticoagulant', 'vitamin K antagonist', 'warfarin', and/or venous thromboembolism. The outcome of interest was recurrent VTE. Pooled risk ratios (RR) were pooled and analyzed using a random effects model. RESULTS: Eight studies including 26,350 patients were included in this analysis. For incidence of recurrent VTE in the study population, pooled RR was 0.87 (0.60-1.24). For recurrent VTE in non-elderly patients, pooled RR was 0.52 (0.27-0.99). Significant heterogeneity of 91% was noted for this outcome. For recurrent VTE in elderly patients, pooled RR was 0.56 (0.33-0.94). Significant heterogeneity of 71% was noted for this outcome. The heterogeneity persisted for recurrent VTE in both elderly and non-elderly patients despite adjusting for specific DOAC used. CONCLUSIONS: Moderate-to-high quality evidence suggests DOAC use was associated with a statistically significant reduction in the incidence of recurrent VTE in elderly and non-elderly patients. Significant heterogeneity noted for the outcome of interest indicates the reduction in VTE could be due to chance. CLINICAL IMPLICATIONS: Further randomized trials with elderly and non-elderly patients are needed to determine if DOAC use in patients with VTE is truly non-inferior to warfarin in this important subgroup of patients.

Chest, 2018

To evaluate if sex influences the efficacy and safety of direct oral anticoagulant use for extend... more To evaluate if sex influences the efficacy and safety of direct oral anticoagulant use for extended thromboprophylaxis (ET) against venous thromboembolism (VTE) in acutely ill medical patients METHODS: We searched several databases from inception to 31 December 2017 to identify comparative studies evaluating direct oral anticoagulants for ET against VTE in acutely ill medical patients. Only randomized controlled trials were included in this systematic review and meta-analysis. Outcomes of interest were total VTE events and major bleeding. Adjusted odds ratios (OR) were pooled and analyzed using a random effects model. RESULTS: We included 3 randomized controlled trials with 17,305 patients (8,659 males and 8,646 females). For total VTE events in males, pooled OR (95% confidence interval) was 0.79 (0.65-0.96). For total VTE events in females, pooled OR (95% confidence interval) was 0.63 (0.44-0.90). For major bleeding in males, pooled OR (95% confidence interval) was 1.34 (0.51-3.51). For major bleeding in females, pooled OR (95% confidence interval) was 2.74 (1.90-3.96). CONCLUSIONS: Sex-related differences do exist for the efficacy and safety of direct oral anticoagulant for extended thromboprophylaxis in acutely ill medical patients. Female and male patients have a lower risk for VTE events with direct oral anticoagulant use for extended thromboprophylaxis. While females have fewer VTE events with ET compared to males, the clinically and statistically significant increased for major bleeding obviates this benefit. CLINICAL IMPLICATIONS: Extended thromboprophylaxis in acutely ill medical patients remains a topic of great debate. Our current meta-analysis highlights the ongoing need to determine subgroups of patients that benefit from use of direct oral anticoagulants for extended thromboprophylaxis without increasing the risk for bleeding.

Southern Medical Journal, 2019

Acknowledgements Foreword Principal recommendations Introduction Chapter 1-Method and data return... more Acknowledgements Foreword Principal recommendations Introduction Chapter 1-Method and data returns Chapter 2-Organisational data Key Findings Chapter 3-Prospective data 3.1 Total population data 3.2 Outcome data 3.3 Risk 3.4 The surgery undertaken Key Findings Recommendations Chapter 4-Peer review case data 4.1 Descriptive data 4.2 Outcome of peer review cases 4.3 Overall assessment of care 4.4 Risk assessment 4.5 Pre-operative assessment 4.6 Consent 4.7 Pre-operative phase 4.8 Intra-operative phase 4.9 Postoperative phase Key Findings Recommendations Summary References Appendix 1-Glossary Appendix 2-Six month outcome data Appendix 3-Role and structure of NCEPOD Appendix 4-Hospital participation This report, published by NCEPOD, could not have been achieved without the support of a wide range of individuals who have contributed to this study. Our particular thanks go to:

Gastroenterology, 2017

Background: Hepatic encephalopathy (HE) is a leading cause of readmission due to recurrence despi... more Background: Hepatic encephalopathy (HE) is a leading cause of readmission due to recurrence despite standard of care (SOC, lactulose+rifaximin). These pts also receive multiple antibiotic courses & develop lasting cognitive injury. Fecal microbiota transplantation (FMT) is a promising approach but there is a paucity of data. Aim: To define the safety profile, impact on liver and cognition of FMT for recurrent HE using a rationally-derived stool donor. Methods: Using cross-sectional HE microbiome data, the ideal OpenBiome donor for HE pts (with highest autochthonous taxa) was identified using Random Forrest analysis. Recurrent HE outpts on SOC were randomized to FMT or SOC under an FDA IND. The FMT arm received 5-days of broad-spectrum antibiotics then a single FMT enema(90ml) from the same donor. Follow-up occurred Day 5,6,12,35 & 150, post-randomization. Outcomes included safety, cognition, microbiome & urinary metabolomics. Results: 20 cirrhotic men (all on lactulose, rifaximin & PPI, last HE 4 mths ago) were randomized 1:1 to FMT or SOC. Both arms (FMT vs SOC) were similar in age(64 vs 63), MELD(12.3 vs 13), albumin(3.2 vs 3.1) & alcoholic etiology (6 vs 7). Hospitalizations: Overall, 10 hospitalizations (median 100, IQR 83 days) occurred in the SOC arm (4 HE, 2 variceal bleeding, 2 chest pain,1 diarrhea,1 anemia) compared to 1 FMT (83 days FMT-unrelated, p=0.001). FMT arm: Antibiotics & FMT were well tolerated without related serious adverse events. There was a significant cognitive improvement on PHES & Stroop App in FMT but not in the SOC arm compared to baseline (Figure). MELD significantly increased postantibiotics (delta 1.7,p<0.001), but reverted to baseline post-FMT (delta-0.2,p=0.5 day 20). Microbiome analysis showed antibiotic-related autochthonous taxa reduction and Proteobacteria expansion. FMT increased beneficial taxa (Bifidobacteriaceae, Lactobacillaceae).This accompanied a favorable changes in urine metabolomics with reduced microbial products (hippurate & phenylacetylglycine). One pt worsened cognitively; however, they had higher baseline Proteobacteria, which did not respond to FMT & was subsequently hospitalized. SOC arm: No significant microbiota, metabolomic, cognitive or MELD changes were seen in SOC arm. Conclusions: In the first randomized trial, FMT using a single donor identified through a Precision Medicine approach appears to be safe, reduces hospitalizations, improves cognitive function and restores antibiotic-associated microbial changes in recurrent HE Tu1549

Cureus, 2017

Adrenal masses pose a diagnostic challenge. The differential diagnosis includes functional adrena... more Adrenal masses pose a diagnostic challenge. The differential diagnosis includes functional adrenal tumors, incidentally found adrenal masses, metastases from an unknown primary cancer, and abscesses. Infrequently, adrenal gland abscesses have been reported in disseminated nocardiosis affecting immunocompetent and immunocompromised patients. We report a case of disseminated Nocardia farcinica pneumonia with an adrenal gland abscess in an immunocompetent patient with no identified risk factors for nocardiosis.

The American Journal of the Medical Sciences, 2017

bleeding source were 0.84 (0.46 to 1.53), 1.18 (0.64 to 2.16), and 1.49 (0.86 to 2.59), respectiv... more bleeding source were 0.84 (0.46 to 1.53), 1.18 (0.64 to 2.16), and 1.49 (0.86 to 2.59), respectively. Stigmata of recent hemorrhage were more readily identified with urgent colonoscopy OR 2.85 (1.90 to 4.28). There were no differences in requirement for surgery, length of hospital stay or rate of endoscopic intervention. However, these effect sizes were limited by considerable heterogeneity which was probably due to studies being conducted in different countries having different criteria for discharge and on variations in the type of endoscopic therapy for stigmata of recent hemorrhage. Conclusions Among patients with acute LGIB, there is no evidence that urgent colonoscopy reduces mortality, re-bleeding or requirement for surgery or that it improves the rate of identification of the bleeding source. However, urgent colonoscopy does increase the rate of detection of stigmata of recent hemorrhage.

Proceedings of the National Academy of Sciences, 2008

PKCη is expressed predominantly in the epithelial tissues; however, its role in the regulation of... more PKCη is expressed predominantly in the epithelial tissues; however, its role in the regulation of epithelial tight junctions (TJs) is unknown. We present evidence that PKCη phosphorylates occludin on threonine residues (T403 and T404) and plays a crucial role in the assembly and/or maintenance of TJs in Caco-2 and MDCK cell monolayers. Inhibition of PKCη by specific pseudo substrate inhibitor or knockdown of PKCη by specific shRNA disrupts the junctional distribution of occludin and ZO-1 and compromises the epithelial barrier function. Expression of dominant negative, PKCη K394R disrupts the TJ and barrier function, whereas wild-type PKCη and constitutively active PKCη A161E enhance the TJ integrity. Inhibition and knockdown of PKCη or expression of PKCη K394R induce dephosphorylation of occludin on threonine residues, whereas active PKCη elevates occludin phosphorylation. PKCη directly interacts with the C-terminal domain of occludin and phosphorylates it on highly conserved T403 a...

Laboratory Investigation, 2011

The tight junctions of bile duct epithelium form a barrier between the toxic bile and liver paren... more The tight junctions of bile duct epithelium form a barrier between the toxic bile and liver parenchyma. Disruption of tight junctions appears to have a crucial role in the pathogenesis of various liver diseases. In this study, we investigated the disruptive effect of hydrogen peroxide and the protective effect of epidermal growth factor (EGF) on the tight junctions and adherens junctions in the bile duct epithelium. Oxidative stress in NRC-1 and Mz-ChA-1 cell monolayers was induced by administration of hydrogen peroxide. Barrier function was evaluated by measuring electrical resistance and inulin permeability. Integrity of tight junctions, adherens junctions and the actin cytoskeleton was determined by imunofluorescence microscopy. Role of signaling molecules was determined by evaluating the effect of specific inhibitors. Hydrogen peroxide caused a rapid disruption of tight junctions and adherens junctions leading to barrier dysfunction without altering the cell viability. Hydrogen peroxide rapidly increased the levels of p-MLC (myosin light chain) and c-Src(pY418). ML-7 and PP2 (MLCK and Src kinase inhibitors) attenuated hydrogen peroxide-induced barrier dysfunction, tight junction disruption and reorganization of actin cytoskeleton. Pretreatment of cell monolayers with EGF ameliorated hydrogen peroxide-induced tight junction disruption and barrier dysfunction. The protective effect of EGF was abrogated by ET-18-OCH 3 and the Ro-32-0432 (PLCg and PKC inhibitors). Hydrogen peroxide increased tyrosine phosphorylation of ZO-1, claudin-3, E-cadherin and b-catenin, and pretreatment of cells with EGF attenuated tyrosine phosphorylation of these proteins. These results demonstrate that hydrogen peroxide disrupts tight junctions, adherens junctions and the actin cytoskeleton by an MLCK and Src kinase-dependent mechanism in the bile duct epithelium. EGF prevents hydrogen peroxide-induced tight junction disruption by a PLCg and PKC-dependent mechanism.

Journal of Biological Chemistry, 2008

Occludin is phosphorylated on tyrosine residues during the oxidative stress-induced disruption of... more Occludin is phosphorylated on tyrosine residues during the oxidative stress-induced disruption of tight junction, and in vitro phosphorylation of occludin by c-Src attenuates its binding to ZO-1. In the present study mass spectrometric analyses of C-terminal domain of occludin identified Tyr-379 and Tyr-383 in chicken occludin as the phosphorylation sites, which are located in a highly conserved sequence of occludin, YETDYTT; Tyr-398 and Tyr-402 are the corresponding residues in human occludin. Deletion of YETDYTT motif abolished the c-Src-mediated phosphorylation of occludin and the regulation of ZO-1 binding. Y398A and Y402A mutations in human occludin also abolished the c-Src-mediated phosphorylation and regulation of ZO-1 binding. Y398D/ Y402D mutation resulted in a dramatic reduction in ZO-1 binding even in the absence of c-Src. Similar to wild type occludin, its Y398A/Y402A mutant was localized at the plasma membrane and cell-cell contact sites in Rat-1 cells. However, Y398D/Y402D mutants of occludin failed to localize at the cell-cell contacts. Calcium-induced reassembly of Y398D/Y402D mutant occludin in Madin-Darby canine kidney cells was significantly delayed compared with that of wild type occludin or its T398A/T402A mutant. Furthermore, expression of Y398D/Y402D mutant of occludin sensitized MDCK cells for hydrogen peroxide-induced barrier disruption. This study reveals a unique motif in the occludin sequence that is involved in the regulation of ZO-1 binding by reversible phosphorylation of specific Tyr residues. Epithelial tight junctions (TJs) 2 form a selective barrier to the diffusion of toxins, allergens, and pathogens from the external environment into the tissues in the gastrointestinal tract, lung,

Journal of Biological Chemistry, 2007

Occludin is hyperphosphorylated on Ser and Thr residues in intact epithelial tight junction (TJ);... more Occludin is hyperphosphorylated on Ser and Thr residues in intact epithelial tight junction (TJ); however, the role of this phosphorylation in the assembly of TJ is unclear. The influence of protein phosphatases PP2A and PP1 on the assembly of TJ and phosphorylation of occludin was evaluated in Caco-2 cells. Protein phosphatase inhibitors and reduced expression of PP2A-C␣ and PP1␣ accelerated the calcium-induced increase in transepithelial electrical resistance and barrier to inulin permeability and also enhanced the junctional organization of occludin and ZO-1 during TJ assembly. Phosphorylation of occludin on Thr residues, but not on Ser residues, was dramatically reduced during the disassembly of TJ and was gradually increased during the reassembly. PP2A and PP1 co-immunoprecipitate with occludin, and this association was reduced during the assembly of TJ. Glutathione S-transferase (GST) pulldown assay using recombinant GST-occludin demonstrated that cellular PP2A and PP1 bind to the C-terminal tail of occludin, and these interactions were also reduced during the assembly of TJ. A pairwise binding assay using GST-occludin and purified PP2A and PP1 demonstrates that PP2A and PP1 directly interacts with the C-terminal tail of occludin. In vitro incubation of phospho-occludin with PP2A or PP1 indicated that PP2A dephosphorylates occludin on phospho-Thr residues, whereas PP1 dephosphorylates it on phospho-Ser. This study shows that PP2A and PP1 directly interact with occludin and negatively regulate the assembly of TJ by modulating the phosphorylation status of occludin.

Journal of Biological Chemistry, 2012

In the middle column of Fig. 6A, the wrong images were inserted. The corrected figure is shown be... more In the middle column of Fig. 6A, the wrong images were inserted. The corrected figure is shown below. This change does not alter the conclusion of the study.