Publications by authors named "Akshay Gupta"

44 Publications

Syndrome of Inappropriate Antidiuretic Hormone Secretion and Lead Toxicity in a Child With Sickle Cell Disease and Pica.

Cureus 2021 Aug 1;13(8):e16813. Epub 2021 Aug 1.

Division of Medical Toxicology, Department of Emergency and Hospital Medicine, Lehigh Valley Health Network/University of South Florida Morsani College of Medicine, Allentown, USA.

We describe the presentation and management of a three-year-old child with a history of pica, vitamin D deficiency, and sickle cell disease, who was admitted for pyelonephritis, and found to have elevated blood lead level (BLL) of 103.7 µg/dL, and who subsequently developed altered mental status and syndrome of inappropriate antidiuretic hormone secretion (SIADH). In consultation with Medical Toxicology, the patient was chelated with calcium disodium edetate (EDTA) and British Anti Lewisite (BAL). The patient's hyponatremia was managed with hypertonic saline infusion. The patient's encephalopathy improved throughout her hospital course, and she was discharged on hospital day 8. Following five days of EDTA and three days of BAL injections, her repeat BLL was 15.3 µg/dL. SIADH has been associated with severe lead poisoning and may be more likely to occur in high risk patients such as individuals with sickle cell anemia, particularly where medications are used that may cause iatrogenic hyponatremia.
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http://dx.doi.org/10.7759/cureus.16813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425150PMC
August 2021

ExBoX: a simple Boolean exclusion strategy to drive expression in neurons.

J Cell Sci 2021 Sep 13. Epub 2021 Sep 13.

Neuroscience Graduate Program, Department of Molecular, Cell & Systems Biology, University of California, Riverside, CA, USA.

The advent of modern single-cell biology has revealed the striking molecular diversity of cell populations once thought to be more homogeneous. This newly appreciated complexity has made intersectional genetic approaches essential to understanding and probing cellular heterogeneity at the functional level. Here we build on previous knowledge to develop a simple AAV-based approach to define specific subpopulations of cells by Boolean exclusion logic (AND NOT). This Expression by Boolean Exclusion (ExBoX) system encodes for a gene of interest which is turned On by a particular recombinase (Cre or FlpO) and turned Off by another. ExBoX allows for the specific transcription of a gene of interest in cells expressing only the activating recombinase, but not in cells expressing both. We show the ability of the ExBoX system to tightly regulate expression of fluorescent reporters in vitro and in vivo, and further demonstrate the adaptability of the system by achieving expression of a variety of virally-delivered coding sequences in the mouse brain. This simple strategy will expand the molecular toolkit available for cell- and time-specific gene expression in a variety of systems.
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http://dx.doi.org/10.1242/jcs.257212DOI Listing
September 2021

Air pollution perception in ten countries during the COVID-19 pandemic.

Ambio 2021 Jun 21. Epub 2021 Jun 21.

Department of Civil and Environmental Engineering, Virginia Tech, 301-D3 Patton Hall, Blacksburg, VA, 24061, USA.

As largely documented in the literature, the stark restrictions enforced worldwide in 2020 to curb the COVID-19 pandemic also curtailed the production of air pollutants to some extent. This study investigates the perception of the air pollution as assessed by individuals located in ten countries: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the USA. The perceptions towards air quality were evaluated by employing an online survey administered in May 2020. Participants (N = 9394) in the ten countries expressed their opinions according to a Likert-scale response. A reduction in pollutant concentration was clearly perceived, albeit to a different extent, by all populations. The survey participants located in India and Italy perceived the largest drop in the air pollution concentration; conversely, the smallest variation was perceived among Chinese and Norwegian respondents. Among all the demographic indicators considered, only gender proved to be statistically significant.
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http://dx.doi.org/10.1007/s13280-021-01574-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216327PMC
June 2021

Impact of COVID-19 pandemic on mobility in ten countries and associated perceived risk for all transport modes.

PLoS One 2021 1;16(2):e0245886. Epub 2021 Feb 1.

Department of Civil and Environmental Engineering, Virginia Tech, Blacksburg, Virginia, United States of America.

The restrictive measures implemented in response to the COVID-19 pandemic have triggered sudden massive changes to travel behaviors of people all around the world. This study examines the individual mobility patterns for all transport modes (walk, bicycle, motorcycle, car driven alone, car driven in company, bus, subway, tram, train, airplane) before and during the restrictions adopted in ten countries on six continents: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. This cross-country study also aims at understanding the predictors of protective behaviors related to the transport sector and COVID-19. Findings hinge upon an online survey conducted in May 2020 (N = 9,394). The empirical results quantify tremendous disruptions for both commuting and non-commuting travels, highlighting substantial reductions in the frequency of all types of trips and use of all modes. In terms of potential virus spread, airplanes and buses are perceived to be the riskiest transport modes, while avoidance of public transport is consistently found across the countries. According to the Protection Motivation Theory, the study sheds new light on the fact that two indicators, namely income inequality, expressed as Gini index, and the reported number of deaths due to COVID-19 per 100,000 inhabitants, aggravate respondents' perceptions. This research indicates that socio-economic inequality and morbidity are not only related to actual health risks, as well documented in the relevant literature, but also to the perceived risks. These findings document the global impact of the COVID-19 crisis as well as provide guidance for transportation practitioners in developing future strategies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245886PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850470PMC
February 2021

Large cholelithiasis with cholecystoduodenal fistula.

Radiol Case Rep 2021 Mar 8;16(3):661-663. Epub 2021 Jan 8.

Lehigh Valley Health Network, Department of Emergency and Hospital Medicine/USF Morsani College of Medicine, Cedar Crest Boulevard & I-78, Allentown 18103 PA, USA.

Cholelithiasis is a common gastrointestinal pathology that can lead to rare complications including cholecystoduodenal fistulas and GI hemorrhage. Diagnosing cholelithiasis and cholecystoduodenal fistulas in the emergency department (ED) using computed tomography (CT) imaging despite nonspecific and variable symptoms is critical in determining management strategies for medically complex patients. An 87-year-old medically complex female presented to the ED in hemorrhagic shock after several episodes of hematemesis, hematochezia, and other nonspecific gastrointestinal symptoms. A CT of the abdomen/pelvis was performed revealing cholecystitis with a large 6-cm stone; additionally, a biliary enteric fistula was noted with blood products in the gallbladder. This case highlights the importance of CT imaging in the setting of gastrointestinal bleeding with cholelithiasis and biliary enteric fistula diagnosis, and discusses potential management strategies of these diagnoses in medically complex patients.
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http://dx.doi.org/10.1016/j.radcr.2020.12.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809246PMC
March 2021

A survey dataset to evaluate the changes in mobility and transportation due to COVID-19 travel restrictions in Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa, United States.

Data Brief 2020 Dec 24;33:106459. Epub 2020 Oct 24.

Department of Engineering and Science, University of Agder, Jon Lilletuns vei 9, Grimstad, 4879, Agder, Norway.

COVID-19 pandemic has heavily impacted the global community. To curb the viral transmission, travel restrictions have been enforced across the world. The dataset documents the mobility disruptions and the modal shifts that have occurred as a consequence of the restrictive measures implemented in ten countries: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. An online questionnaire was distributed during the period from the 11st to the 31st of May 2020, with a total of 9 394 respondents. The first part of the survey has characterized the frequency of use of all transport modes before and during the enforcement of the restrictions, while the second part of the survey has dealt with perceived risks of contracting COVID-19 from different transport modes and perceived effectiveness of travel mitigation measures. Overall, the dataset (stored in a repository publicly available) can be conveniently used to quantify and understand the modal shifts and people's cognitive behavior towards travel due to COVID-19. The collected responses can be further analysed by considering other demographic and socioeconomic covariates.
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http://dx.doi.org/10.1016/j.dib.2020.106459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607379PMC
December 2020

Dendritic morphology and inhibitory regulation distinguish dentate semilunar granule cells from granule cells through distinct stages of postnatal development.

Brain Struct Funct 2020 Dec 29;225(9):2841-2855. Epub 2020 Oct 29.

Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA.

Semilunar granule cells (SGCs) have been proposed as a morpho-functionally distinct class of hippocampal dentate projection neurons contributing to feedback inhibition and memory processing in juvenile rats. However, the structural and physiological features that can reliably classify granule cells (GCs) from SGCs through postnatal development remain unresolved. Focusing on postnatal days 11-13, 28-42, and > 120, corresponding with human infancy, adolescence, and adulthood, we examined the somato-dendritic morphology and inhibitory regulation in SGCs and GCs to determine the cell-type specific features. Unsupervised cluster analysis confirmed that morphological features reliably distinguish SGCs from GCs irrespective of animal age. SGCs maintain higher spontaneous inhibitory postsynaptic current (sIPSC) frequency than GCs from infancy through adulthood. Although sIPSC frequency in SGCs was particularly enhanced during adolescence, sIPSC amplitude and cumulative charge transfer declined from infancy to adulthood and were not different between GCs and SGCs. Extrasynaptic GABA current amplitude peaked in adolescence in both cell types and was significantly greater in SGCs than in GCs only during adolescence. Although GC input resistance was higher than in SGCs during infancy and adolescence, input resistance decreased with developmental age in GCs, while it progressively increased in SGCs. Consequently, GCs' input resistance was significantly lower than SGCs in adults. The data delineate the structural features that can reliably distinguish GCs from SGCs through development. The results reveal developmental differences in passive membrane properties and steady-state inhibition between GCs and SGCs which could confound their use in classifying the cell types.
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http://dx.doi.org/10.1007/s00429-020-02162-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677165PMC
December 2020

Survey data regarding perceived air quality in Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa, United States before and during Covid-19 restrictions.

Data Brief 2020 Oct 13;32:106169. Epub 2020 Aug 13.

University of Agder, Department of Engineering and Science, Jon Lilletuns vei 9, Grimstad, 4879, Agder, Norway.

The dataset deals with the air quality perceived by citizens before and during the enforcement of COVID-19 restrictions in ten countries around the world: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. An online survey conveniently translated into Chinese, English, Italian, Norwegian, Persian, Portuguese collected information regarding the perceived quality of air pollution according to a Likert scale. The questionnaire was distributed between 11-05-2020 and 31-05-2020 and 9 394 respondents took part. Both the survey and the dataset (stored in a Microsoft Excel Worksheet) are available in a public repository. The collected data offer the people's subjective perspectives related to the objective improvement in air quality occurred during the COVID-19 restrictions. Furthermore, the dataset can be used for research studies involving the reduction in air pollution as experienced, to a different extent, by populations of all the ten countries.
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http://dx.doi.org/10.1016/j.dib.2020.106169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425542PMC
October 2020

Hallway bed status is associated with lower patient satisfaction.

Am J Emerg Med 2020 11 24;38(11):2471-2472. Epub 2020 Feb 24.

Department of Emergency and Hospital Medicine, Lehigh Valley Hospital and Health Network, University of South Florida Morsani, College of Medicine, Allentown, PA, United States of America. Electronic address:

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http://dx.doi.org/10.1016/j.ajem.2020.02.049DOI Listing
November 2020

Unusual left ventricle to left atrial fistula.

Ann Card Anaesth 2020 Jan-Mar;23(1):90-91

Department of Cardiac Anaesthesia, Sir Ganga Ram Hospital, New Delhi, India.

Left ventricular to left atrial fi stula is a very uncommon finding. Most of the cases are secondary to surgical procedures or paravalvular infectious process. The present case depicted an unusual regurgitation (apart from transmitral MR) through LV-LA fistula causing deterioration of the patient's symptoms.
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http://dx.doi.org/10.4103/aca.ACA_130_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034211PMC
March 2021

Real-world cost analysis of endovascular repair versus open repair in patients with nonruptured abdominal aortic aneurysms.

J Vasc Surg 2020 02 3;71(2):432-443.e4. Epub 2019 Jun 3.

Division of Vascular and Endovascular Surgery, Johns Hopkins Medicine, Baltimore, Md; Division of Vascular and Endovascular Surgery, Department of Surgery, University of California San Diego, La Jolla, Calif. Electronic address:

Background: The aim of this study was to provide a nationwide, all-payer, real-world cost analysis of endovascular aortic aneurysm repair (EVAR) versus open aortic aneurysm repair (OAR) in patients with nonruptured abdominal aortic aneurysms (non-rAAA).

Methods: All non-rAAA patients registered between July 2009 and March 2015 in the Premier Healthcare Database were analyzed. The Student t-test and the χ test were used for continuous and categorical variables, respectively; median value comparisons were done with the Wilcoxon-Mann-Whitney rank-sum test. The in-hospital absolute mean total cost (sum of fixed cost and variable cost) and subcategories were analyzed after adjustment for inflation at July 2015. Fixed costs included all overhead costs while variables costs included in-hospital services including procedures, room and board, services provided by hospital staff, and pharmacy costs. Total cost was stratified based on admission type (emergency vs nonemergency), 75th percentile of length of hospital stay among individual procedures (expected vs extended stay), mortality, and complications. Student t-test and Fisher's analysis of variance were used for comparing mean cost. Year-wise comparison of mean cost was done with analysis of variance to look for a trend over time.

Results: Our study cohort included 38,809 non-rAAA patients (33,171 EVAR and 5638 OAR). The mean total cost of index admission was lower in EVAR in comparison with OAR ($32,052 vs $36,091; P < .001), with lower fixed costs ($11,309 vs $16,818; P < .001) and higher variable costs ($20,743 vs $19,272; P < .001). Cost of pharmacy, labor, operating room, room and board and other costs were significantly higher with OAR, whereas the supply cost was higher with EVAR. The expected hospital length of stay of patients who underwent EVAR was associated with a higher total cost ($27,271 vs $25,680; P < .001) and a higher variable cost ($18,186 vs $13,671; P < .001) than OAR patients. However, the extended hospital stay of patients who underwent EVAR had lower costs in all categories compared with the extended length of stay of those who underwent OAR. Mortality associated with EVAR was costlier than OAR associated mortality (mean $72,483 vs $59,804; P = .017). From 2009 to 2014, the mean total cost of EVAR increased significantly by 18.5% ($28,745 vs $34,049; P < .001) owing to a 7.8% increase in fixed costs ($10,931 vs $11,789; P < .001) and a 25.0% increase in variable costs ($17,804 vs $22,257; P < .001). The mean total cost OAR remained stable over time.

Conclusions: Overall hospitalization costs associated with EVAR of non-rAAA was lower than the hospitalization cost of OAR. Interestingly, we found that, among patients who had an expected hospital length of stay, the hospitalization cost after OAR was significantly lower than after EVAR. The average hospitalization cost of OAR was stable during the 5 years study period, whereas the hospitalization cost of EVAR increased significantly over time. Further studies are required to identify reasons for increased costs associated with EVAR.
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http://dx.doi.org/10.1016/j.jvs.2018.12.059DOI Listing
February 2020

Real-world evidence of superiority of endovascular repair in treating ruptured abdominal aortic aneurysm.

J Vasc Surg 2018 07 20;68(1):74-81. Epub 2018 Mar 20.

The Johns Hopkins Bayview, Vascular and Endovascular Surgery Clinical Research Center, Baltimore, Md. Electronic address:

Objective: The majority of previous studies, including randomized controlled trials, have failed to provide sufficient evidence of superiority of endovascular aneurysm repair (EVAR) over open aortic repair (OAR) of ruptured abdominal aortic aneurysm (rAAA) while comparing mortality and complications. This is in part due to small study size, patient selection bias, scarce adjustment for essential variables, single insurance type, or selection of only older patients. This study aimed to provide real-world, contemporary, comprehensive, and robust evidence on mortality of EVAR vs OAR of rAAA.

Methods: A retrospective observational cohort study was performed of rAAA patients registered in the Premier Healthcare Database between July 2009 and March 2015. A multivariate logistic regression model was operated to estimate the association between procedure types (OAR vs EVAR) and in-hospital mortality. The final model was adjusted for demographics (age, sex, race, marital status, and geographic region), hospital characteristics (urban or rural, teaching or not), and potential confounders (hypertension, diabetes, hypercholesterolemia, obesity, ischemic heart disease, chronic kidney disease, symptoms of critical limb ischemia, chronic obstructive pulmonary disease, smoking, and alcoholism). Furthermore, coarsened exact matching was applied to substantiate the result in the matched cohort.

Results: There were a total of 3164 patients with rAAA (1550 [49.0%] OAR and 1614 [51.0%] EVAR). Mortality was 23.79% in the EVAR group compared with 36.26% in the OAR group (P < .001). The adjusted odds ratios of mortality (1.91; 95% confidence interval [CI], 1.62-2.25; P < .001), cardiac complication (1.54; 95% CI, 1.22-1.96; P < .001), pulmonary failure (1.90; 95% CI, 1.60-2.24; P < .001), renal failure (1.90; 95% CI, 1.61-2.23; P < .001), and bowel ischemia (2.40; 95% CI, 1.70-3.35; P < .001) were significantly higher after OAR compared with EVAR. We further applied coarsened exact matching, which followed the same pattern of mortality (odds ratio, 1.68; 95% CI 1.41-1.99; P < .001) and all major complications.

Conclusions: Although the choice of repair of rAAA is highly dependent on the experience of the operating team and the anatomic suitability of the patient, this contemporary analysis of a large cohort of rAAA showed significantly higher adjusted risk of mortality in OAR compared with EVAR and substantially higher complications.
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http://dx.doi.org/10.1016/j.jvs.2017.11.065DOI Listing
July 2018

Converging early responses to brain injury pave the road to epileptogenesis.

J Neurosci Res 2019 11 29;97(11):1335-1344. Epub 2017 Nov 29.

Department of Pharmacology, Physiology & Neuroscience, Rutgers New Jersey Medical School, Newark, NJ.

Epilepsy, characterized by recurrent seizures and abnormal electrical activity in the brain, is one of the most prevalent brain disorders. Over two million people in the United States have been diagnosed with epilepsy and 3% of the general population will be diagnosed with it at some point in their lives. While most developmental epilepsies occur due to genetic predisposition, a class of "acquired" epilepsies results from a variety of brain insults. A leading etiological factor for epilepsy that is currently on the rise is traumatic brain injury (TBI), which accounts for up to 20% of all symptomatic epilepsies. Remarkably, the presence of an identified early insult that constitutes a risk for development of epilepsy provides a therapeutic window in which the pathological processes associated with brain injury can be manipulated to limit the subsequent development of recurrent seizure activity and epilepsy. Recent studies have revealed diverse pathologies, including enhanced excitability, activated immune signaling, cell death, and enhanced neurogenesis within a week after injury, suggesting a period of heightened adaptive and maladaptive plasticity. An integrated understanding of these processes and their cellular and molecular underpinnings could lead to novel targets to arrest epileptogenesis after trauma. This review attempts to highlight and relate the diverse early changes after trauma and their role in development of epilepsy and suggests potential strategies to limit neurological complications in the injured brain.
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http://dx.doi.org/10.1002/jnr.24202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975115PMC
November 2019

Immunostaining of Biocytin-filled and Processed Sections for Neurochemical Markers.

J Vis Exp 2016 12 31(118). Epub 2016 Dec 31.

Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School;

Electrophysiological recordings of cells using the patch clamp technique have allowed for the identification of different neuronal types based on firing patterns. The inclusion of biocytin/neurobiotin in the recording electrode permits post-hoc recovery of morphological details, which are necessary to determine the dendritic arborization and the regions targeted by the axons of the recorded neurons. However, given the presence of morphologically similar neurons with distinct neurochemical identities and functions, immunohistochemical staining for cell-type-specific proteins is essential to definitively identify neurons. To maintain network connectivity, brain sections for physiological recordings are prepared at a thickness of 300 µm or greater. However, this thickness often hinders immunohistological postprocessing due to issues with antibody penetration, necessitating the resectioning of the tissue. Resectioning of slices is a challenging art, often resulting in the loss of tissue and morphology of the cells from which electrophysiological data was obtained, rendering the data unusable. Since recovery of morphology would limit data loss and guide in the selection of neuronal markers, we have adopted a strategy of recovering cell morphology first, followed by secondary immunostaining. We introduce a practical approach to biocytin filling during physiological recordings and subsequent serial immunostaining for the recovery of morphology, followed by the restaining of sections to determine the neurochemical identity. We report that sections that were filled with biocytin, fixed with paraformaldehyde (PFA), stained, and coverslipped can be removed and restained with a second primary antibody days later. This restaining involves the removal of the coverslip, the washing of sections in a buffer solution, and the incubation of primary and secondary antibodies to reveal the neurochemical identity. The method is advantageous for eliminating data loss due to an inability to recover morphology and for narrowing down the neurochemical markers to be tested based on morphology.
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http://dx.doi.org/10.3791/54880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264554PMC
December 2016

Parachute Tricuspid Valve: A Case Treated by Open Heart Surgery.

Ann Thorac Surg 2016 Nov;102(5):e443-e445

Department of Paediatric Cardiac Sciences, Sir Ganga Ram Hospital, New Delhi, India. Electronic address:

Parachute valve is the malformation of an atrioventricular valve in which the tension apparatus springs from a single papillary muscle or group of muscles. Parachute tricuspid valve is a rare anomaly with no surgically repaired case to date. We describe a case of parachute deformity of the tricuspid valve leading to hemodynamically significant severe tricuspid stenosis. The present case was successfully repaired surgically along with atrial septal defect (ASD) and ventricular septal defect (VSD) closure.
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http://dx.doi.org/10.1016/j.athoracsur.2016.03.113DOI Listing
November 2016

Arterialization of central venous pressure waveform.

Ann Card Anaesth 2016 Oct-Dec;19(4):760-761

Department of Cardiac Surgery, Sir Ganga Ram Hospital, New Delhi, India.

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http://dx.doi.org/10.4103/0971-9784.191556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070347PMC
March 2017

Assessing Angle's malocclusion among cleft lip and/or palate patients in Jammu.

J Int Soc Prev Community Dent 2016 Apr;6(Suppl 1):S23-7

Department of Public Health Dentistry, Luxmi Bai Institute of Dental Sciences and Hospital, Patiala, Punjab, India.

Objective: The study was conducted to examine the patients with abnormalities of cleft lip and/or palate and its association with different types of malocclusion.

Materials And Methods: This descriptive study was done among 168 patients with abnormalities of cleft lip and/or palate. Angle's classification of malocclusion was applied for assessment of occlusion as Class I, Class II, and Class III. The types of oral clefts classification such as cleft lip unilateral and cleft lip bilateral, cleft palate (CP), unilateral cleft lip with palate (UCLP) and bilateral cleft lip with palate (BCLP) was considered. Chi-square test was applied to analyze the data at P < 0.05.

Results: The study showed different categories of clefts patients as cleft lip (81), CP (31), and both cleft lip and palate (53). The occurrence of unilateral cleft lip (44) was maximum among the sample followed by UCLP (39), and bilateral cleft lip (31). Maximum subjects with Class II (10.7%) and Class III (4.9%) malocclusion were seen with unilateral cleft lip deformities. None of the patients with UCLP had Class III malocclusion.

Conclusion: Cleft lip was the most commonly observed deformity and high frequency of Class II and III malocclusion was evident. Therefore, patients with such abnormalities should be screened timely.
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http://dx.doi.org/10.4103/2231-0762.181163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863479PMC
April 2016

Hepatic Ultrasonography for Surveillance in Patients With Uveal Melanoma.

JAMA Ophthalmol 2016 Feb;134(2):174-80

Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

Importance: There is a lack of information regarding the role of systemic surveillance in patients with primary uveal melanoma.

Objective: To evaluate the utility of serial hepatic ultrasonography (USG) for detection of asymptomatic liver metastases in patients undergoing surveillance after primary treatment of uveal melanoma.

Design, Setting, And Participants: Retrospective cohort study reviewing data from patients with primary uveal melanoma treated between October 2003 and October 2012 at a multispecialty tertiary care center. Patients were managed using a standardized protocol. Initial staging was done with contrast-enhanced computed tomography of the chest, abdomen, and pelvis. This was followed by periodic surveillance with hepatic USG and liver function tests scheduled every 6 months for the first 5 years and annually thereafter. Abnormal surveillance hepatic USG findings were categorized as (1) cyst or hemangioma, (2) indeterminate lesion, (3) suspicious for metastasis, or (4) consistent with metastasis. If indicated, hepatic USG abnormalities were confirmed by additional imaging modalities (confirmatory scans) such as computed tomography or magnetic resonance imaging. Liver biopsy was performed only if the confirmatory scan was positive.

Main Outcomes And Measures: Sensitivity, specificity, and positive predictive value of hepatic USG for detecting asymptomatic liver metastases.

Results: In 263 patients (121 men, 142 women; mean [SD] age at diagnosis, 61.1 [13.9] years), a total of 1390 hepatic USGs were performed, with a mean of 5.3 per patient (range, 1-17 per patient). Overall, 86 hepatic USGs of 71 patients (27%) were reported as abnormal. Of the 13 lesions identified as a cyst/hemangioma and 17 as indeterminate, 1 was found to be metastatic in each group (8% and 6%, respectively). Of 36 patients with findings suspicious for metastasis, 23 (64%) had metastasis confirmed. All 5 patients (100%) with findings consistent with metastasis had biopsy-proven metastasis. The sensitivity, specificity, and positive predictive value of hepatic USG for findings that were indeterminate or suspicious for metastasis were 96% (95% CI, 80%-99%), 88% (95% CI, 83%-91%), and 45% (95% CI, 33%-59%), respectively. Specificity of the confirmatory scan was greater than that of hepatic USG (93% [95% CI, 89%-96%] vs 88% [95% CI, 83%-91%], respectively; P < .001). Only 4 of 30 patients (13%) with metastasis had abnormal findings on simultaneous liver function tests.

Conclusions And Relevance: A stepwise surveillance protocol based on serial hepatic USGs followed by confirmatory scans offers high likelihood of detecting asymptomatic metastases in patients with primary uveal melanoma.
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http://dx.doi.org/10.1001/jamaophthalmol.2015.4810DOI Listing
February 2016

Endoscopic therapy of neoplasia related to Barrett's esophagus and endoscopic palliation of esophageal cancer.

Cancer Control 2013 Apr;20(2):117-29

Section of Endoscopic Oncology, Gastrointestinal Tumor Program, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

Background: Barrett's esophagus (BE) is the most important identifiable risk factor for the progression to esophageal adenocarcinoma.

Methods: This article reviews the current endoscopic therapies for BE with high-grade dysplasia and intramucosal cancer and briefly discusses the endoscopic palliation of advanced esophageal cancer.

Results: The diagnosis of low-grade or high-grade dysplasia (HGD) is based on several cytologic criteria that suggest neoplastic transformation of the columnar epithelium. HGD and carcinoma in situ are regarded as equivalent. The presence of dysplasia, particularly HGD, is also a risk factor for synchronous and metachronous adenocarcinoma. Dysplasia is a marker of adenocarcinoma and also has been shown to be the preinvasive lesion. Esophagectomy has been the conventional treatment for T1 esophageal cancer and, although debated, is an appropriate option in some patients with HGD due to the presence of occult cancer in over one-third of patients.

Conclusions: Endoscopic ablative modalities (eg, photodynamic therapy and cryoablation) and endoscopic resection techniques (eg, endoscopic mucosal resection) have demonstrated promising results. The significant morbidity and mortality of esophagectomy makes endoscopic treatment an attractive potential option.
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http://dx.doi.org/10.1177/107327481302000205DOI Listing
April 2013

Prevalence of adenomas and advanced adenomas in patients in the 40- to 49-year age group undergoing screening colonoscopy because of a family history of adenoma/polyp in a first-degree relative.

Gastrointest Endosc 2012 Apr;75(4):705-11

Division of Gastroenterology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

Background: Per current guidelines, patients with a first-degree relative (FDR) with adenomas should get screened at age 40. Data on the prevalence of adenomas and advanced adenomas (AAs) in these patients are lacking.

Objective: To examine the prevalence of adenomas and AAs in 40- to 49-year-old individuals undergoing screening colonoscopy because of a family history (FH) of polyps and to compare these data with those of a control population of similar age.

Design: Retrospective cross-sectional study.

Setting: Tertiary care academic medical center and Veterans Affairs medical center.

Patients: Study subjects included all 40- to 49-year-old asymptomatic individuals undergoing initial screening colonoscopy at our institution from January 1, 2006, to June 1, 2009, because of an FDR with polyps. The control population consisted of all 40- to 49-year-old individuals who underwent their first colonoscopy during the same period because of abdominal pain, diarrhea, or constipation without an FH of polyps or colorectal cancer.

Intervention: Colonoscopy.

Main Outcome Measurements: The prevalence of adenomas of any size, AAs, and risk factors associated with adenomas.

Results: The prevalence of adenomas was greater in the FH of polyps group (n = 176) compared with the control sample (n = 178) (26.7% vs 13.5%; P = .002) but was not statistically greater for AAs (5.7% vs 3.4%; P = .3). After adjusting for confounders, FH of a polyp was associated with an increased prevalence of adenomas (odds ratio 2.8 [95% CI, 1.4-5.5]).

Limitations: Limited data on polyp histology in FDRs and limited sample size.

Conclusions: Among 40- to 49-year-old patients undergoing screening colonoscopy because of an FDR with polyps, the prevalence of adenomas was greater than in a control population. Prospective research is needed to quantify the prevalence of AAs in this group and to determine whether these individuals should undergo screening colonoscopy at age 40.
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http://dx.doi.org/10.1016/j.gie.2012.01.046DOI Listing
April 2012

Decrease in tonic inhibition contributes to increase in dentate semilunar granule cell excitability after brain injury.

J Neurosci 2012 Feb;32(7):2523-37

Department of Neurology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.

Brain injury is an etiological factor for temporal lobe epilepsy and can lead to memory and cognitive impairments. A recently characterized excitatory neuronal class in the dentate molecular layer, semilunar granule cell (SGC), has been proposed to regulate dentate network activity patterns and working memory formation. Although SGCs, like granule cells, project to CA3, their typical sustained firing and associational axon collaterals suggest that they are functionally distinct from granule cells. We find that brain injury results in an enhancement of SGC excitability associated with an increase in input resistance 1 week after trauma. In addition to prolonging miniature and spontaneous IPSC interevent intervals, brain injury significantly reduces the amplitude of tonic GABA currents in SGCs. The postinjury decrease in SGC tonic GABA currents is in direct contrast to the increase observed in granule cells after trauma. Although our observation that SGCs express Prox1 indicates a shared lineage with granule cells, data from control rats show that SGC tonic GABA currents are larger and sIPSC interevent intervals shorter than in granule cells, demonstrating inherent differences in inhibition between these cell types. GABA(A) receptor antagonists selectively augmented SGC input resistance in controls but not in head-injured rats. Moreover, post-traumatic differences in SGC firing were abolished in GABA(A) receptor blockers. Our data show that cell-type-specific post-traumatic decreases in tonic GABA currents boost SGC excitability after brain injury. Hyperexcitable SGCs could augment dentate throughput to CA3 and contribute substantively to the enhanced risk for epilepsy and memory dysfunction after traumatic brain injury.
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http://dx.doi.org/10.1523/JNEUROSCI.4141-11.2012DOI Listing
February 2012

Prevalence of any size adenomas and advanced adenomas in 40- to 49-year-old individuals undergoing screening colonoscopy because of a family history of colorectal carcinoma in a first-degree relative.

Gastrointest Endosc 2011 Jul 23;74(1):110-8. Epub 2011 Apr 23.

Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA.

Background: Per current guidelines, patients with a first-degree relative (FDR) with colorectal cancer (CRC) should get screened at least at age 40. Data about the prevalence of adenomas and advanced adenomas (AAs) in these patients are lacking.

Objective: To examine the prevalence of adenomas and AAs in 40- to 49-year-old individuals undergoing screening colonoscopy for family history of CRC.

Design: Retrospective chart review.

Patients: Asymptomatic patients 40 to 49 years of age undergoing their first screening colonoscopy at the University of Michigan during the period 1999 to 2009 because of an FDR with CRC.

Main Outcome Measurements: Prevalence of adenomas (any size), AAs, and risk factors associated with adenomas.

Results: Among 640 study patients, the prevalence of adenomas (any size) was 15.4% and 3.3% for AAs. Adenoma prevalence was lower if the FDR with CRC was younger than 60 years of age versus an FDR with CRC older than 60 years of age (12.4% vs 19%, P = .034). Male sex (odds ratio 2.6; 95% CI, 1.06-4.4) and advancing age (odds ratio 1.16; 95% CI, 1.03-1.31) were associated with adenomas.

Limitations: Limited data on risk factor exposure and insufficient sample size to assess risk factors for AAs.

Conclusions: Among 40- to 49-year-old patients undergoing screening colonoscopy because of an FDR with CRC, the prevalence of adenomas and AAs is low. Further research should determine whether these individuals have a higher prevalence of adenomas compared with average-risk individuals.
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http://dx.doi.org/10.1016/j.gie.2011.02.010DOI Listing
July 2011

Magnesium sensitive, adenosine resistant, repetitive monomorphic ventricular tachycardia.

Pacing Clin Electrophysiol 2009 Dec 10;32(12):e28-30. Epub 2009 Sep 10.

Department of Medicine, Section of Cardiology, Clinical Cardiac Electrophysiology Service, Rush University Medical Center, Chicago, Illinois, USA.

Repetitive monomorphic ventricular tachycardia (RMVT) is characterized by episodes of ventricular ectopy and nonsustained VT exacerbated by catecholamines. Because this arrhythmia is frequently adenosine sensitive, its mechanism is believed to be cyclic adenosine monophosphate-mediated triggered activity due to delayed afterdepolarizations. We present a case of RMVT associated with significant hypomagnesemia (serum level = 1.1 mg/dL), which did not respond to intravenous (IV) adenosine and terminated repeatedly after IV magnesium. Electrophysiologic study demonstrated an origin from the left sinus of Valsalva, which was successfully ablated. The combination of adenosine resistance and magnesium sensitivity may be consistent with an atypical RMVT mechanism related to inhibition of sodium-potassium adenosine triphosphatase (Na(+)-K(+) ATPase).
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http://dx.doi.org/10.1111/j.1540-8159.2009.02527.xDOI Listing
December 2009

Survival benefit from early revascularization in elderly patients with cardiogenic shock after acute myocardial infarction: a cohort study.

J Invasive Cardiol 2009 Jul;21(7):305-12

John H. Stroger Jr. Hospital of Cook County, Chicago, IL 60612, USA.

Objectives: To assess if early revascularization offers any survival benefit in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) who are > or = 75 years of age.

Background: CS after AMI continues to pose formidable therapeutic challenges in elderly patients.

Methods: We conducted survival analyses of 310 consecutive subjects (including 80 patients > or = 75 years of age) who developed cardiogenic shock after AMI at two study centers - Rush University Medical Center and the John H. Stroger Jr. Hospital of Cook County (both in Chicago, Illinois). The data were collected over a 6-year period. Where appropriate, we used Kaplan-Meier survival plots, multivariate Cox proportional hazards modeling, stepwise multivariate Poisson regression analyses and unconditional logistic regression analysis.

Results: Early revascularization was associated with a statistically significant survival benefit both in patients < 75 years of age (relative hazard 0.40, 95% confidence interval [CI] 0.28-0.59; p < 0.001), as well as in patients > or = 75 years of age (relative hazard 0.56, 95% CI 0.32-0.99; p = 0.049). This benefit remained significant even after adjusting for the simultaneous effects of several putative confounders. In patients > or = 75 years of age, this survival benefit was evident very early and was sustained all through the period of follow up of the cohort.

Conclusions: These retrospective data suggest a significant survival benefit of early revascularization in elderly patients > or = 75 years of age developing CS after AMI, albeit less as compared to those aged < 75 years.
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July 2009

Reliability and accuracy of the endoscopic appearance in the identification of aberrant crypt foci.

Gastrointest Endosc 2009 Aug 21;70(2):322-30. Epub 2009 Jun 21.

Department of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA.

Background: Aberrant crypt foci (ACF) have emerged as a putative precursor to colorectal adenoma, with potential use as a biomarker of colorectal cancer. However, there are wide differences in ACF prevalence, dysplasia, and histologic confirmation rates across studies. These differences may, in part, be because of variability in identification of endoscopic criteria.

Objective: To systematically evaluate the accuracy and reliability of various endoscopic criteria used to identify ACF when using magnification chromoendoscopy (MCE).

Design: Images obtained via MCE were shown to participating endoscopists who diagnosed them as ACF or not and who assessed them for the endoscopic characteristics used to identify ACF in the literature.

Main Outcome Measurements: The predictive ability of the endoscopic criteria (crypt number, staining, margin, crypt size, epithelial thickness, and lumen shape) for histologic confirmation of ACF, and their reliability across endoscopists. The accuracy of the examiners in identifying ACF that were histologically confirmed was also assessed.

Results: The interrater agreement rate for all except one of the endoscopic criteria (crypt number) was low and did not improve with training. None of the criteria could significantly predict histologic confirmation of ACF. Despite training exercises, accuracy of endoscopists to correctly identify a histologically proven ACF remained low.

Limitations: Still images with x40 optical magnification were analyzed rather than real-time endoscopy. All ACF samples were hyperplastic; none were dysplastic.

Conclusions: No endoscopic criteria evaluated by our study predicted histologic confirmation of ACF. MCE had low accuracy and poor reliability.
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http://dx.doi.org/10.1016/j.gie.2008.12.060DOI Listing
August 2009

Isthmus dependent atrial flutter cycle length correlates with right atrial cross-sectional area.

Indian Pacing Electrophysiol J 2009 May 15;9(3):167-73. Epub 2009 May 15.

Department of Internal Medicine, Section of Cardiology, Cardiac Electrophysiology Service, 1750 W. Harrison, Suite 983 Jelke, Chicago, Illinois 60612, USA.

Background: Right atrial flutter cycle length can prolong in the presence of antiarrhythmic drug therapy. We hypothesized that the cycle length of right atrial isthmus dependent flutter would correlate with right atrial cross-sectional area measurements.

Methods: 60 patients who underwent ablation for electrophysiologically proven isthmus dependent right atrial flutter, who were not on Class I or Class III antiarrhythmic drugs and had recent 2-dimensional echocardiographic data comprised the study group. Right atrial length and width were measured in the apical four chamber view. Cross-sectional area was estimated by multiplying the length and width. 35 patients had an atrial flutter rate >/= 250 bpm (Normal Flutter Group) and 25 patients had an atrial flutter rate < 250 bpm (Slow Flutter Group).

Results: Mean atrial flutter rate was 283 bpm in the normal flutter group and 227 bpm in the slow flutter group. Mean atrial flutter cycle length was 213 ms in the Normal Flutter Group and 265 ms in the Slow Flutter Group (p< 0.0001). Mean right atrial cross sectional area was 1845 mm(2) in the Normal Flutter group and 2378 mm(2) in the Slow Flutter Group, (p< 0.0001). Using linear regression, CSA was a significant predictor of cycle length (beta =0.014 p = 0.0045). For every 1 mm(2) increase in cross-sectional area, cycle length is 0.014 ms longer.

Conclusions: In the absence of antiarrhythmic medications, right atrial cross sectional area enlargement correlates with atrial flutter cycle length. These findings provide further evidence that historical rate-related definitions of typical isthmus dependent right atrial are not mechanistically valid.
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May 2009

Aberrant crypt foci: are they intermediate endpoints of colon carcinogenesis in humans?

Curr Opin Gastroenterol 2009 Jan;25(1):59-65

Department of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA.

Purpose Of Review: There is a wealth of literature, both from epidemiological and molecular studies, which support the role of aberrant crypt foci (ACF) as a putative precursor to colorectal adenomas and a potential biomarker for colorectal carcinoma. In this review, we critically examine the evidence on employing ACF as an intermediate endpoint.

Recent Findings: Recent, larger-scale, multicenter studies of ACF have raised questions about ACF. The prevalence of ACF has not correlated with colorectal adenomas, and the technique for ACF detection using high-magnification chromoendoscopy has demonstrated considerable variability across endoscopists and over time. Dysplastic ACF, once postulated as the ACF destined for adenomatous transformation, have been rarely identified in US individuals, in contrast to European and Japanese investigations. A substantial percentage of purported, endoscopically detected ACF have not been confirmed on histologic review. Finally, molecular characterization of ACF has been studied on only a limited basis.

Summary: ACF remain a potential biomarker for colorectal cancer, but similar to other biomarkers under development, additional study of ACF is needed before reliable, clinical application can be assured.
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http://dx.doi.org/10.1097/MOG.0b013e32831db286DOI Listing
January 2009

Rescue permanent iliac vein pacing after epicardial lead failure: an unusual reversal of pacing fortune.

Europace 2008 Oct 7;10(10):1236-8. Epub 2008 Jul 7.

Department of Electrophysiology, Rush University Medical Center, 1750 West Harrison Street, Chicago, IL 60612, USA.

Surgical lead placement is generally considered as a last resort for patients who require permanent pacing and who are unable to accommodate transvenous leads. The technique is limited by the need for direct epicardial access and reduced reliability of epicardial leads (compared with modern transvenous leads) [Belott and Reynolds. Permanent pacemaker and implantable cardioverter defibrillator implantation. In Ellenbogen KA, Kay GN, Lau CP, Wilkoff BL (eds). Clinical Cardiac Pacing, Defibrillation, and Resynchronization Therapy. Philadelphia: Saunders Elsevier, 2007; pp. 561-651]. We report a patient with limited venous access and a poorly functioning epicardial ventricular lead, who was successfully upgraded to a dual-chamber endocardial pacing system via the iliac vein. Pacemaker lead implantation from the iliac vein is an often overlooked option for patients with limited central venous access. In our patient, a pacing upgrade was achieved after the presumptive final option had been exhausted.
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http://dx.doi.org/10.1093/europace/eun185DOI Listing
October 2008
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