Publications by authors named "Amit A Patel"

27 Publications

  • Page 1 of 1

Potent anti-inflammatory effects of an H S-releasing naproxen (ATB-346) in a human model of inflammation.

FASEB J 2021 10;35(10):e21913

Division of Medicine, Centre for Clinical Pharmacology and Therapeutics, University College London, London, UK.

ATB-346 is a hydrogen sulfide-releasing non-steroidal anti-inflammatory drug (H S-NSAID) derived from naproxen, which in preclinical studies has been shown to have markedly reduced gastrointestinal adverse effects. However, its anti-inflammatory properties in humans compared to naproxen are yet to be confirmed. To test this, we used a dermal model of acute inflammation in healthy, human volunteers, triggered by ultraviolet-killed Escherichia coli. This robust model allows quantification of the cardinal signs of inflammation along with cellular and humoral factors accumulating within the inflamed skin. ATB-346 was non-inferior to naproxen in terms of its inhibition of cyclooxygenase activity as well as pain and tenderness. ATB-346 significantly inhibited neutrophil infiltration at the site of inflammation at 4 h, compared to untreated controls. Subjects treated with ATB-346 also experienced significantly reduced pain and tenderness compared to healthy controls. Furthermore, both classical and intermediate monocyte subsets infiltrating the site of inflammation at 48 h expressed significantly lower levels of CD14 compared to untreated controls, demonstrating a shift toward an anti-inflammatory phenotype. Collectively, we have shown for the first time in humans that ATB-346 is potently anti-inflammatory and propose that ATB-346 represents the next generation of H S-NSAIDs, as a viable alternative to conventional NSAIDs, with reduced adverse effects profile.
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http://dx.doi.org/10.1096/fj.201902918RRDOI Listing
October 2021

Intradermal lipopolysaccharide challenge as an acute in vivo inflammatory model in healthy volunteers.

Br J Clin Pharmacol 2021 Jul 22. Epub 2021 Jul 22.

Centre for Human Drug Research, Leiden, the Netherlands.

Aims: Whereas intravenous administration of Toll-like receptor 4 ligand lipopolysaccharide (LPS) to human volunteers is frequently used in clinical pharmacology studies, systemic use of LPS has practical limitations. We aimed to characterize the intradermal LPS response in healthy volunteers, and as such qualify the method as local inflammation model for clinical pharmacology studies.

Methods: Eighteen healthy male volunteers received 2 or 4 intradermal 5 ng LPS injections and 1 saline injection on the forearms. The LPS response was evaluated by noninvasive (perfusion, skin temperature and erythema) and invasive assessments (cellular and cytokine responses) in skin biopsy and blister exudate.

Results: LPS elicited a visible response and returned to baseline at 48 hours. Erythema, perfusion and temperature were statistically significant (P < .0001) over a 24-hour time course compared to saline. The protein response was dominated by an acute interleukin (IL)-6, IL-8 and tumour necrosis factor response followed by IL-1β, IL-10 and interferon-γ. The cellular response consisted of an acute neutrophil influx followed by different monocyte subsets and dendritic cells.

Discussion: Intradermal LPS administration in humans causes an acute, localized and transient inflammatory reaction that is well-tolerated by healthy volunteers. This may be a valuable inflammation model for evaluating the pharmacological activity of anti-inflammatory investigational compounds in proof of pharmacology studies.
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http://dx.doi.org/10.1111/bcp.14999DOI Listing
July 2021

Monocytes, macrophages, dendritic cells and neutrophils: an update on lifespan kinetics in health and disease.

Immunology 2021 07 15;163(3):250-261. Epub 2021 Mar 15.

Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel.

Phagocytes form a family of immune cells that play a crucial role in tissue maintenance and help orchestrate the immune response. This family of cells can be separated by their nuclear morphology into mononuclear and polymorphonuclear phagocytes. The generation of these cells in the bone marrow, to the blood and finally into tissues is a tightly regulated process. Ensuring the adequate production of these cells and their timely removal is key for both the initiation and resolution of inflammation. Insight into the kinetic profiles of innate myeloid cells during steady state and pathology will permit the rational development of therapies to boost the production of these cells in times of need or reduce them when detrimental.
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http://dx.doi.org/10.1111/imm.13320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207393PMC
July 2021

Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes.

J Exp Med 2020 09;217(9)

Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, UK.

The human liver contains specialized subsets of mononuclear phagocytes (MNPs) and T cells, but whether these have definitive features of tissue residence (long-term retention, lack of egress) and/or can be replenished from the circulation remains unclear. Here we addressed these questions using HLA-mismatched liver allografts to discriminate the liver-resident (donor) from the infiltrating (recipient) immune composition. Allografts were rapidly infiltrated by recipient leukocytes, which recapitulated the liver myeloid and lymphoid composition, and underwent partial reprogramming with acquisition of CD68/CD206 on MNPs and CD69/CD103 on T cells. The small residual pool of donor cells persisting in allografts for over a decade contained CX3CR1hi/CD163hi/CD206hi Kupffer cells (KCs) and CXCR3hi tissue-resident memory T cells (TRM). CD8+ TRM were found in the local lymph nodes but were not detected egressing into the hepatic vein. Our findings inform organ transplantation and hepatic immunotherapy, revealing remarkably long-lived populations of KCs and TRM in human liver, which can be additionally supplemented by their circulating counterparts.
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http://dx.doi.org/10.1084/jem.20200050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478732PMC
September 2020

Inherited and Environmental Factors Influence Human Monocyte Heterogeneity.

Front Immunol 2019 7;10:2581. Epub 2019 Nov 7.

The Institute of Dental Sciences, Hebrew University, Jerusalem, Israel.

Blood monocytes develop in the bone marrow before being released into the peripheral circulation. The circulating monocyte pool is composed of multiple subsets, each with specialized functions. These cells are recruited to repopulate resident monocyte-derived cells in the periphery and also to sites of injury. Several extrinsic factors influence the function and quantity of monocytes in the blood. Here, we outline the impact of sex, ethnicity, age, sleep, diet, and exercise on monocyte subsets and their function, highlighting that steady state is not a single physiological condition. A clearer understanding of the relationship between these factors and the immune system may allow for improved therapeutic strategies.
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http://dx.doi.org/10.3389/fimmu.2019.02581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854020PMC
September 2020

A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils.

Immunity 2019 04 27;50(4):1069-1083.e8. Epub 2019 Mar 27.

Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, Biopolis, Singapore 138648, Singapore; Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A(∗)STAR), 11 Mandalay Rd., Singapore 308232, Singapore. Electronic address:

Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here, we examined the roles of dermal cDC1s and cDC2s during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1s, but not cDC2s, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine vascular endothelial growth factor α (VEGF-α) by a minor subset of activated EpCAMCD59Ly-6D cDC1s. Neutrophil recruitment by dermal cDC1s was also observed during S. aureus, bacillus Calmette-Guérin (BCG), or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation.
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http://dx.doi.org/10.1016/j.immuni.2019.03.001DOI Listing
April 2019

Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte Subsets.

Front Immunol 2019 1;10:188. Epub 2019 Mar 1.

Division of Medicine, University College London, London, United Kingdom.

The phagosome microenvironment maintains enzyme activity and function. Here we compared the phagosomal pH of human neutrophils, monocytes, dendritic cells (DC), and monocyte-derived cells. An unexpected observation was the striking difference in phagosomal environment between the three monocytes subsets. Classical monocytes and neutrophils exhibited alkaline phagosomes, yet non-classical monocytes had more acidic phagosomes, while intermediate monocytes had a phenotype in-between. We next investigated the differences between primary naïve DC vs. monocyte-derived DC (MoDC) and established that both these cells had acidic phagosomal environments. Across all phagocytes, alkalinization was dependent upon the activity of the NADPH oxidase activity, demonstrated by the absence of NADPH oxidase from a patient with chronic granulomatous disease (CGD) or the use of a pharmacological inhibitor, diphenylene iodonium (DPI). Interestingly, MoDC stimulated with bacterial lipopolysaccharide had increased phagosomal pH. Overall, the increase in alkalinity within the phagosome was associated with increased oxidase activity. These data highlight the heterogeneous nature and potential function of phagocytic vacuoles within the family of mononuclear phagocytes.
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http://dx.doi.org/10.3389/fimmu.2019.00188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405516PMC
January 2020

Fine needle aspirates comprehensively sample intrahepatic immunity.

Gut 2019 08 28;68(8):1493-1503. Epub 2018 Nov 28.

Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London, UK.

Objective: In order to refine new therapeutic strategies in the pipeline for HBV cure, evaluation of virological and immunological changes compartmentalised at the site of infection will be required. We therefore investigated if liver fine needle aspirates (FNAs) could comprehensively sample the local immune landscape in parallel with viable hepatocytes.

Design: Matched blood, liver biopsy and FNAs from 28 patients with HBV and 15 without viral infection were analysed using 16-colour multiparameter flow cytometry.

Results: The proportion of CD4 T, CD8 T, Mucosal Associated Invariant T cell (MAIT), Natural Killer (NK) and B cells identified by FNA correlated with that in liver biopsies from the same donors. Populations of Programmed Death-1 (PD-1)CD39 tissue-resident memory CD8 T cells (CD69CD103) and liver-resident NK cells (CXCR6T-betEomes), were identified by both FNA and liver biopsy, and not seen in the blood. Crucially, HBV-specific T cells could be identified by FNAs at similar frequencies to biopsies and enriched compared with blood. FNAs could simultaneously identify populations of myeloid cells and live hepatocytes expressing albumin, Scavenger Receptor class B type 1 (SR-B1), Programmed Death-Ligand 1 (PD-L1), whereas hepatocytes were poorly viable after the processing required for liver biopsies.

Conclusion: We demonstrate for the first time that FNAs identify a range of intrahepatic immune cells including locally resident sentinel HBV-specific T cells and NK cells, together with PD-L1-expressing hepatocytes. In addition, we provide a scoring tool to estimate the extent to which an individual FNA has reliably sampled intrahepatic populations rather than contaminating blood. The broad profiling achieved by this less invasive, rapid technique makes it suitable for longitudinal monitoring of the liver to optimise new therapies for HBV.
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http://dx.doi.org/10.1136/gutjnl-2018-317071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691856PMC
August 2019

Monocyte and Neutrophil Isolation, Migration, and Phagocytosis Assays.

Curr Protoc Immunol 2018 Aug 3;122(1):e53. Epub 2018 Jul 3.

University College London, Gower Street, London, United Kingdom.

This article describes methods for isolating mouse monocytes and neutrophils, as well as in vitro protocols for measuring cell phagocytosis, migration, and polarization. The method employed here for the isolation of naive phagocytes overcomes many of the difficulties previously encountered concerning phagocyte activation. Three in vitro protocols are provided for the analysis of cell migration, one requiring no specialized equipment, one requiring a modified Boyden chamber, and the other employing a flow chamber, which measures cell adhesion, rolling, and migration. Three in vitro protocols to examine phagocytosis have been included in this updated version. Finally, a method is provided for imaging polarized cells by confocal microscopy. © 2018 by John Wiley & Sons, Inc.
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http://dx.doi.org/10.1002/cpim.53DOI Listing
August 2018

Oral bioavailability enhancement of agomelatine by loading into nanostructured lipid carriers: Peyer's patch targeting approach.

Int J Nanomedicine 2018 15;13(T-NANO 2014 Abstracts):35-38. Epub 2018 Mar 15.

Department of Pharmaceutics and Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, Gujarat, India.

Agomelatine (AGM) is a new antidepressant drug with a novel mechanism of action and fewer side effects compared with older antidepressants. AGM is a melatonin receptor (MT1 and MT2) agonist and 5-hydroxytryptamine receptor (5-HT) antagonist. In the present study, the enhancement of the oral bioavailability of AGM was formulated and loaded into nanostructured lipid carriers (NLCs), using ultrasonication method. In vitro and ex vivo drug release was performed using a dialysis bag and rat duodenum, respectively. Our pharmacodynamic study showed that AGM-NLCs are more efficacious than a pure drug and marketed product, and confocal microscopy revealed lymphatic uptake of AGM-NLCs. The present study concluded that the NLCs enhanced the oral bioavailability of AGM (6.5-fold) by avoiding its first-pass metabolism by way of lymphatic uptake.
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http://dx.doi.org/10.2147/IJN.S124703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863623PMC
May 2018

Nanomedicine for Intranasal Delivery to Improve Brain Uptake.

Curr Drug Deliv 2018 ;15(4):461-469

Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT Campus Changa, Anand - 388 421, Gujarat, India.

Intranasal drug delivery system provides distinct advantage over conventional drug delivery system for a drug that is pharmacokenetically or biologically unstable. Major concern for the treatment of central nervous system diseases is, low concentration of therapeutically active molecule within brain as blood brain barrier is creating obstacle, where intranasal drug delivery provides direct transport of therapeutically active moiety into brain via olfactory or trigeminal pathway. Nasal mucosa provides distinct advantages like improved bioavailability, law dose and quick onset of action and high patient compliance, and the major disadvantage is residence time of drug and irreversible entrapment of drug. This article provides anatomical and physiological information about nasal route and various factors. Article discusses various types of nanoparticles used intranasally and moreover article also emphasizes patents, formulation under development and some.
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http://dx.doi.org/10.2174/1567201814666171013150534DOI Listing
October 2018

The fate and lifespan of human monocyte subsets in steady state and systemic inflammation.

J Exp Med 2017 Jul 12;214(7):1913-1923. Epub 2017 Jun 12.

Division of Medicine, University College London, University of London, London, England, UK

In humans, the monocyte pool comprises three subsets (classical, intermediate, and nonclassical) that circulate in dynamic equilibrium. The kinetics underlying their generation, differentiation, and disappearance are critical to understanding both steady-state homeostasis and inflammatory responses. Here, using human in vivo deuterium labeling, we demonstrate that classical monocytes emerge first from marrow, after a postmitotic interval of 1.6 d, and circulate for a day. Subsequent labeling of intermediate and nonclassical monocytes is consistent with a model of sequential transition. Intermediate and nonclassical monocytes have longer circulating lifespans (∼4 and ∼7 d, respectively). In a human experimental endotoxemia model, a transient but profound monocytopenia was observed; restoration of circulating monocytes was achieved by the early release of classical monocytes from bone marrow. The sequence of repopulation recapitulated the order of maturation in healthy homeostasis. This developmental relationship between monocyte subsets was verified by fate mapping grafted human classical monocytes into humanized mice, which were able to differentiate sequentially into intermediate and nonclassical cells.
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http://dx.doi.org/10.1084/jem.20170355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502436PMC
July 2017

IncobotulinumtoxinA Injection for Temporomandibular Joint Disorder.

Ann Otol Rhinol Laryngol 2017 Apr 1;126(4):328-333. Epub 2017 Feb 1.

1 New York Center for Voice and Swallowing Disorders, New York, New York, USA.

Objectives: Temporomandibular disorder (TMD) involves dysfunction of the temporomandibular joint and associated muscles of mastication causing pain with chewing, limitation of jaw movement, and pain. While the exact pathophysiology of TMD is not completely understood, it is thought that hyperfunction of the muscles of mastication places stress on the temporomandibular joint, leading to degeneration of the joint and associated symptoms. We hypothesize that chemodenervation of the muscles of mastication with IncobotulinumtoxinA (Xeomin) will decrease the stress on the temporomandibular joint and improve pain associated with temporomandibular joint and muscle disorder (TMJD).

Methods: Twenty patients were randomized to IncobotulinumtoxinA (170 units) or saline injection of the masticatory muscles. Patient-reported pain scale (0-10) was recorded at 4-week intervals following injection for 16 weeks. Patients who received saline injection initially were assessed for reduction in pain at the first 4-week interval and if still had significant pain were rolled over into the IncobotulinumtoxinA arm.

Results: Preinjection pain scores were similar between patients. While there was a statistically significant reduction in pain score in the placebo group one month, there was an overall larger drop in average pain scores in those patients injected with IncobotulinumtoxinA initially. All patients initially injected with placebo crossed over into the IncobotulinumtoxinA group. Similar results were seen when examining the composite masticatory muscle tenderness scores. There was no significant change in usage of pain medication.

Conclusions: We demonstrate utility of IncobotulinumtoxinA in treating patients with TMD with pain despite pain medication usage and other conventional treatments.
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http://dx.doi.org/10.1177/0003489417693013DOI Listing
April 2017

Directed balloon cytology of the esophagus: A novel device for obtaining circumferential cytologic sampling.

Laryngoscope 2017 05 16;127(5):1032-1035. Epub 2017 Jan 16.

Head and Neck Surgical Group, New York, New York, U.S.A.

Objective: Current methods of obtaining esophageal cytology include brush biopsy and blind balloon sampling, among others. These methods can be time-consuming if performed in accordance with acknowledged standards. Further, exact site localization can prove to be difficult. We describe a novel device for esophageal sampling using an esophageal balloon with debriding strips contained within the pleats of the balloon. Inflation brings the latter in contact with the surface to be sampled. Cell capture was compared with the commonly used brush technique in a pig model.

Methods: Separate balloon and standard brush cytology samples were collected from a pig model. Smear and cell pellet preparations were compared regarding cell density and total volume.

Results: Adequate samples were obtained with both the brush and balloon. On the cell smear preparations, the cell density was greater when obtained with balloon sampling. Further, the cell pellet volume was significantly greater with the latter as well. The intact morphology of individual rafts of squamous epithelial cells also was comparable between the two methods. In addition, the balloon provided precise mapping of the cytology sites in contrast to the standard brush technique.

Conclusion: We present an innovative new balloon technology for esophageal sampling, which demonstrated a decreased sampling time interval, precise mapping, and increased cellular volume when compared to a commonly used brush technique.

Level Of Evidence: NA. Laryngoscope, 127:1032-1035, 2017.
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http://dx.doi.org/10.1002/lary.26472DOI Listing
May 2017

Gender differences in onabotulinum toxin A dosing for adductor spasmodic dysphonia.

Laryngoscope 2017 05 16;127(5):1131-1134. Epub 2016 Sep 16.

New York Center for Voice and Swallowing Disorders, New York, New York, U.S.A.

Objectives/hypothesis: The objective of this study was to determine the influence of gender on onabotulinum toxin A dosing for the treatment of adductor spasmodic dysphonia symptoms.

Study Design: Retrospective review.

Methods: A chart review of the senior author's database of botulinum toxin injections was performed. Patients diagnosed with adductor spasmodic dysphonia who received onabotulinum toxin A (BoNTA) injections to the thyroarytenoid muscle for at least 5 years were included for study. Patients who received alternate formulations of botulinum toxin (Myobloc, Dysport, or Xeomin) and patients with alternate diagnoses, such as abductor spasmodic dysphonia, tremor, and oromandibular dystonia, were excluded. The average BoNTA dose was calculated for each patient and statistical analysis was performed comparing the male and female groups.

Results: A total of 201 patients (52 males and 149 females) met inclusion criteria. The average follow-up times for the male and female groups were 10.2 ± 3.6 and 11.1 ± 4 years, respectively. The average BoNTA doses for the male and female groups were 0.6 ± 0.42 U and 1.3 ± 1.1 U, respectively. Statistical analysis was performed using an independent samples two-tailed t test yielding a P value of .0000000002. A large effect size was noted with Cohen's d = 0.85.

Conclusions: The data from this retrospective chart review reveal a statistically and clinically significant correlation between female gender and higher average BoNTA dose for symptom control in adductor spasmodic dysphonia. Explanations for this observation are speculative and include a possible inverse relationship between optimal BoNTA dose and vocal fold mass and possibly greater neutralizing antibody formation among female patients.

Level Of Evidence: 4. Laryngoscope, 127:1131-1134, 2017.
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http://dx.doi.org/10.1002/lary.26265DOI Listing
May 2017

Laryngology in Art: The Portrait of Dr Wilhelm Mayer-Hermann.

Authors:
Amit A Patel

Otolaryngol Head Neck Surg 2016 12 23;155(6):1012-1013. Epub 2016 Aug 23.

Head & Neck Surgical Group, New York, New York, USA

Otto Dix's portrait of the laryngologist Dr Wilhelm Mayer-Hermann represents a shining example of Neue Sachlichkeit, or New Objectivity, offering a return to unsentimental reality and a focus on the objective world, as opposed to the more abstract and idealistic tendencies of expressionism. However, precious little is known about the subject of the portrait. This article examines the portrait and attempts to shed light on the life and career of the Dr Wilhelm Mayer-Hermann.
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http://dx.doi.org/10.1177/0194599816665575DOI Listing
December 2016

Subglottic Squamous Cell Carcinoma: A Population-Based Study of 889 Cases.

Otolaryngol Head Neck Surg 2016 Feb 25;154(2):315-21. Epub 2015 Nov 25.

Department of Otolaryngology-Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, USA

Objective: Subglottic squamous cell carcinoma (SCCa) is a rare malignancy representing <5% of all laryngeal cancers. Patients often present with late-stage disease, and survival outcomes are reportedly worse than those for SCCa in other regions of the larynx.

Study Design: Analysis of a population-based tumor registry.

Setting: Academic medical center.

Subjects And Methods: The US National Cancer Institute's Surveillance, Epidemiology, and End Results database was queried for cases of subglottic SCCa from 1973 to 2011 (889 cases). Resulting data were analyzed, including patient demographics, therapeutic measures, and survival outcomes.

Results: Subglottic SCCa most frequently occurred in the fifth to seventh decade of life, with a mean age at diagnosis of 65.7 ± 11.3 years. There was a strong male predilection, with a male:female ratio of 3.83:1. Most patients were stage III and IV (64.4%) per the American Joint Committee on Cancer. The most common treatment modality was a combination of radiotherapy and surgery (38.8%), followed by radiotherapy alone (33.9%), and surgery alone (17.0%). Overall 5-year disease-specific survival rate was 53.7%. When stratified by treatment modality, 5-year disease-specific survival was 62.4% for surgery alone, 56.7% for radiotherapy alone, and 55.1% for surgery with adjuvant radiotherapy (P = .3892).

Conclusion: This study represents the largest cohort of subglottic SCCa. It shows a strong predilection for men in the US population. Surgery with adjuvant radiotherapy was the most commonly employed treatment modality. No statistically significant differences were observed in 5-year DSS by treatment modality.
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http://dx.doi.org/10.1177/0194599815618190DOI Listing
February 2016

Endoscopic palliative decompression of the cavernous sinus in a rare case of a metastatic renal cell carcinoma to the clivus.

Br J Neurosurg 2015 Jun 9;29(3):430-1. Epub 2014 Dec 9.

Department of Neurological Surgery, Rutgers New Jersey Medical School , Newark, NJ , USA.

We present a rare case of acute cavernous sinus syndrome due to a renal cell carcinoma metastasis to the clivus. This case highlights the role of palliative endoscopic endonasal decompression of the cavernous sinus to relieve cranial neuropathies, obtain tissue diagnosis, and for cytoreduction in preparation for additional adjuvant therapy.
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http://dx.doi.org/10.3109/02688697.2014.987217DOI Listing
June 2015

Nodular lymphocyte predominant hodgkin lymphoma: biology, diagnosis and treatment.

Clin Lymphoma Myeloma Leuk 2014 Aug 3;14(4):261-70. Epub 2014 Feb 3.

Department of Hematology and Oncology, St Luke's Roosevelt Hospital Center, New York, NY; Mt Sinai Health System.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon variant of classical Hodgkin lymphoma. It is characterized histologically by presence of lymphohistiocytic cells which have B-cell phenotype, are positive for CD19, CD20, CD45, CD79a, BOB.1, Oct.2, and negative for CD15 and CD30. Patients often present with early stage of disease and do not have classical B symptoms. The clinical behavior appears to mimic that of an indolent non-Hodgkin lymphoma more than that of classical Hodgkin disease. The purpose of the present report is to define the biology of NLPHL, review its clinical presentation, and summarize the available clinical data regarding treatment.
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http://dx.doi.org/10.1016/j.clml.2014.01.006DOI Listing
August 2014

Laryngeal chondrosarcoma: a population-based analysis.

Laryngoscope 2014 Aug 11;124(8):1877-81. Epub 2014 Mar 11.

Department of Otolaryngology-Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey.

Objectives/hypothesis: Laryngeal chondrosarcoma (LC) is a rare entity, reportedly comprising less than 1% of all laryngeal tumors. Consequently, the incidence and survival of patients with this slow-growing tumor has been difficult to study. Our objective was to evaluate incidence, organized by patient demographics, as well as long-term survival trends of this malignancy using a population-based database.

Study Design: Retrospective analysis of the United States National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry.

Methods: The SEER database was searched for patients diagnosed with LC between 1973 and 2010. Data analyzed included patient demographics, incidence, treatment modality, and survival.

Results: One-hundred and forty-three cases were identified, representing 0.2% of all laryngeal tumors. Median age at diagnosis was 61.7 years. Men and women constituted 76.2% and 23.8% of patients, respectively. Tumors were locally invasive with 37.7% T4 disease and infrequent regional and distant metastases. The 1-year, 5-year, and 10-year disease-specific survival for LC was 96.5%, 88.6%, and 84.8%, respectively, compared to 88.3%, 68.2%, and 59.3%, respectively for patients with all other laryngeal tumors (P values < 0.01). Relative survival was 94.9% at 1 year, 88.5% at 5 years, and 88.4% at 10 years.

Conclusions: This analysis represents the largest LC study sample to date, allowing for evaluation of incidence and long-term survival. LC occurs infrequently, is locally invasive, but only rarely metastasizes. Prognosis for LC is significantly better than for other laryngeal malignancies.
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http://dx.doi.org/10.1002/lary.24618DOI Listing
August 2014

Early harvesting of the vascularized pedicled nasoseptal flap during endoscopic skull base surgery.

Am J Otolaryngol 2013 May-Jun;34(3):188-94. Epub 2013 Jan 16.

Department of Otolaryngology - Head & Neck Surgery, University of Medicine and Dentistry of New Jersey - New Jersey Medical School, Newark, NJ, USA.

Purpose: The vascularized pedicled nasoseptal flap (PNSF) represents a successful option for reconstruction of large skull base defects after expanded endoscopic endonasal approaches (EEA). This vascularized flap can be harvested early or late in the operation depending on the anticipation of high-flow CSF leaks. Each harvesting technique (early vs. late) is associated with different advantages and disadvantages. In this study, we evaluate our experience with early harvesting of the PNSF for repair of large skull base defects after EEA.

Methods: A retrospective review was performed at a tertiary care medical center on patients who underwent early PNSF harvesting during reconstruction of intraoperative high-flow CSF leaks after EEA between December 2008 and March 2012. Demographic data, repair materials, surgical approach, and incidence of PNSF usage were collected.

Results: Eighty-seven patients meeting the inclusion criteria were identified. In 86 procedures (98.9%), the PNSF harvested at the beginning of the operation was used. In 1 case (1.1%), the PNSF was not used because a high-flow intraoperative CSF leak was not encountered. This patient had recurrence of intradural disease 8months later, and the previously elevated PNSF was subsequent used after tumor resection.

Conclusion: Based on our data, a high-flow CSF leak and need for a PNSF can be accurately anticipated in patients undergoing EEA for skull base lesions. Because of the advantages of early harvesting of the PNSF and the high preoperative predictive value of CSF leak anticipations, this technique represents a feasible harvesting practice for EEA surgeries.
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http://dx.doi.org/10.1016/j.amjoto.2012.10.005DOI Listing
October 2013

Celebrating the golden anniversary of anterior skull base surgery: reflections on the past 50 years and its historical evolution.

Laryngoscope 2013 Jan;123(1):64-72

Department of Otolaryngology-Head and Neck Surgery, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA.

With its inception nearly half a century ago through the pioneering work of Dandy, McLean, and Smith, anterior skull base (ASB) surgery is a relatively young discipline. It became a distinct entity in 1963 when Ketcham popularized the combined transcranial transfacial approach for en bloc resection of tumors of the paranasal sinuses extending into the anterior cranial fossa. However, because these procedures resulted in major morbidities and mortalities, alternative modes of treatment were sought. Since the 1970s, the introduction and promotion of the surgical endoscope by Messerklinger, Stammberger, and Kennedy, commenced the era of endoscopic sinus surgery. Thaler and colleagues described the utility of the endoscope for ASB surgery at the turn of the century. This allowed direct visualization and safer, more accurate removal of tumors. In 2001, Casiano reported the first purely endoscopic endonasal ASB resection, a novel technique that has been adopted by major skull base centers. The success of ASB surgery can be attributed to both the development of the skull base team as well as improvements in surgical techniques, instrumentation, and visualization technology. In this article, we review the historical evolution of ASB surgery as we approach the 50th anniversary since its recognition as a distinct entity.
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http://dx.doi.org/10.1002/lary.23687DOI Listing
January 2013

Endoscopic endonasal resection of extensive anterior skull base sinonasal osteoblastoma.

Otolaryngol Head Neck Surg 2012 Sep 26;147(3):594-6. Epub 2012 Mar 26.

Department of Otolaryngology-Head and Neck Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103, USA.

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http://dx.doi.org/10.1177/0194599812442125DOI Listing
September 2012

Reliability using the universal classification of acute myocardial infarction compared to ST-segment classification.

Cardiovasc Revasc Med 2011 Jul-Aug;12(4):210-6. Epub 2011 Jan 26.

Washington Hospital Center, Georgetown University, Washington, DC 20010, USA.

Objectives: To study the inter-physician reliability using the universal classification (UC) of acute myocardial infarction (AMI) compared to the ST-segment classification (STC). The UC is based on clinical, electrocardiographic (ECG), and pathophysiologic characteristics compared to the STC, which is mainly ECG based.

Methods: In this registry of consecutive patients with AMI presenting to a tertiary hospital, we studied the inter-physician reliability [weighted kappa (wK)] using the UC and the STC. Two physician investigators independently classified each patient with AMI according to the UC and STC, and a third senior physician investigator resolved any disagreement.

Results: The study included Type 1=226 (89.7%), Type 2=16 (6.3%), Type 3=3 (1.2%), Type 4a=1 (0.4%), Type 4b=4 (1.6%), Type 5=2 (0.8%), ST-segment-elevation AMI (STEMI)=140 (55.6%), and non-ST-segment-elevation AMI (NSTEMI)=112 (44.4%). Inter-physician reliability using the UC was very good (wK=0.84, 95% CI 0.68-0.99) and using the STC was good (wK=0.78, 95% CI 0.70-0.86). Of patients with Type 1 AMI, 57.1% were STEMI and 42.9% were NSTEMI. In contrast, of patients with Type 2 AMI, 18.8% were STEMI and 81.2% were NSTEMI.

Conclusion: The UC is a reliable method to classify patients with AMI and performs better than the STC in this study. Validation of the two classifications should be performed in large prospective studies.
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http://dx.doi.org/10.1016/j.carrev.2010.06.002DOI Listing
December 2011

The universal classification is an independent predictor of long-term outcomes in acute myocardial infarction.

Cardiovasc Revasc Med 2011 Jan-Feb;12(1):35-40. Epub 2010 Oct 20.

Washington Hospital Center, Georgetown University, Washington, DC 20010, USA.

Background: The long-term outcomes of patients with acute myocardial infarction (AMI) according to the universal classification (UC) are unknown. We investigated whether the outcome of these patients is better predicted by the UC than the ST-segment classification (STC).

Methods: We conducted a retrospective study of 348 consecutive patients with AMI with mean follow-up of 30.6 months. The primary outcome was major adverse cardiovascular events (MACE) [composite of all causes of death and AMI].

Results: The study included ST-segment elevation (STEMI) = 168 (48%), non-ST-segment elevation (NSTEMI) = 180 (52%), Type 1 = 278 (80%), Type 2 = 55 (15.8%), Type 3 = 5 (1.4%), Type 4a = 2 (0.6%), Type 4b = 5 (1.4%), and Type 5 = 3 (0.9%). During follow-up, 102 (29.3%) patients had MACE, 80 (23%) patients died, and 31 (8.9%) had an AMI. The adjusted risk of MACE was similar for NSTEMI and STEMI (HR 1.26, 95% CI 0.77-2.03, P = .35) but was significantly lower for patients with Type 2 AMI as compared to Type 1 (HR 0.44, 95% CI 0.21-0.90, P= .02). The UC, peak troponin levels, discharge glomerular filtration rate <60 ml/min per 1.73 m(2), and thrombolysis in myocardial infarction risk score were independent predictors of MACE (all, P<.05).

Conclusions: The UC is an independent predictor of long-term outcomes in AMI patients compared to the STC. Type 2 AMI has less than half the risk of MACE as Type 1 AMI. Future studies should report outcomes of AMI patients according to the UC types.
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http://dx.doi.org/10.1016/j.carrev.2009.11.006DOI Listing
May 2011

Systemic approaches for multifocal bronchioloalveolar carcinoma: is there an appropriate target?

Oncology (Williston Park) 2010 Sep;24(10):888-98, 900

Albert Einstein College of Medicine, New York, New York, USA.

Bronchioloalveolar carcinoma (BAC) is a subset of pulmonary adenocarcinoma characterized by distinct and unique pathological, molecular, radiographic, and clinical features. While the incidence of pure BAC is rare, comprising only 1% to 4% of non-small-cell lung cancer (NSCLC), mixed subtypes (including BAC with focal invasion and adenocarcinoma with BAC features) represent as much as 20% of adenocarcinomas--and that figure may be increasing. Despite the longstanding recognition of this entity, there is no established treatment paradigm for patients with multifocal BAC, resulting in competing approaches and treatment controversies. Current options for multifocal BAC include both surgery and systemic therapies. Unfortunately, prospective data on systemic approaches are limited by study design and small patient numbers; there are only seven phase II studies involving four therapies. This article evaluates key characteristics of BAC, including the current understanding of histopathology and tumor biology. In addition, it comprehensively reviews the systemic phase II studies in an attempt to clarify the therapeutic challenges in this disease. It also includes the first proposed treatment paradigm that integrates both EGFR mutational status and the sub-histologies, mucinous and nonmucinous BAC.
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September 2010

Quartiles of peak troponin are associated with long-term risk of death in type 1 and STEMI, but not in type 2 or NSTEMI patients.

Clin Cardiol 2009 Oct;32(10):575-83

East Carolina Heart Institute at East Carolina University, Greenville, North Carolina 27834, USA.

Background: The prognostic value of peak cardiac troponin (cTn) in different types of acute myocardial infarction (AMI) under the universal clinical classification is unknown.

Hypothesis: We tested the hypothesis that the prognostic value of cTn varies with its peak level and type of AMI.

Methods: We studied 345 consecutive patients with AMI with mean follow-up of 30.6 months according to quartiles of peak cTn level (QPTL) and the type of AMI. The study outcomes were the major adverse cardiovascular events (MACE; composite of all causes of mortality and recurrent AMI) and the individual components of MACE.

Results: The study included patients with AMI Type 1 (n = 276), type 2 (n = 54), ST-segment elevation myocardial infarction (STEMI; n = 159), and non-ST-segment elevation myocardial infarction (NSTEMI; n = 186). Overall, peak cTn level was an independent predictor of MACE (hazard ratio [HR]: 1.001, 95% confidence interval [CI]: 1.000-1.003, P = 0.01) and death (HR: 1.002, 95% CI: 1.001-1.004, P = 0.003), but not of recurrent AMI. The highest risk of MACE and death was in the highest QPTL (61.6%, P = .016 and 66.3%, P = 0.021, respectively) while the highest risk of recurrent AMI was in the lowest QPTL (83.7%, P = 0.04). Quartiles of peak cTn level were significantly associated with increased risk of MACE and death in patients with Type 1 (all P = 0.01) and STEMI (P = 0.01 and P = 0.02, respectively), but no association existed in type 2 or NSTEMI patients.

Conclusions: Overall, peak cTn predicts the risk of MACE and death but not the risk of AMI. While in Type 1 and STEMI patients, QPTL are associated with risk of MACE and death, no association exists in type 2 or NSTEMI patients.
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http://dx.doi.org/10.1002/clc.20662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652998PMC
October 2009
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