Publications by authors named "Steven Sullivan"

67 Publications

The effectiveness of malaria camps as part of the Durgama Anchalare Malaria Nirakaran (DAMaN) program in Odisha, India: study protocol for a cluster-assigned quasi-experimental study.

Glob Health Action 2021 Jan;14(1):1886458

School of Global Public Health, New York University, New York, NY, USA.

The Indian state of Odisha has a longstanding battle with forest malaria. Many remote and rural villages have poor access to health care, a problem that is exacerbated during the rainy season when malaria transmission is at its peak. Approximately 62% of the rural population consists of tribal groups who are among the communities most negatively impacted by malaria. To address the persistently high rates of malaria in these remote regions, the Odisha State Malaria Control Program introduced 'malaria camps' in 2017 where teams of health workers visit villages to educate the population, enhance vector control methods, and perform village-wide screening and treatment. Malaria rates declined statewide, particularly in forested areas, following the introduction of the malaria camps, but the impact of the intervention is yet to be externally evaluated. This study protocol describes a cluster-assigned quasi-experimental stepped-wedge study with a pretest-posttest control group design that evaluates if malaria camps reduce the prevalence of malaria, compared to control villages which receive the usual malaria control interventions (e.g. IRS, ITNs), as detected by PCR.
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http://dx.doi.org/10.1080/16549716.2021.1886458DOI Listing
January 2021

Implementing a Telehospitalist Program Between Veterans Health Administration Hospitals: Outcomes, Acceptance, and Barriers to Implementation.

J Hosp Med 2021 Mar;16(3):156-163

VA Office of Rural Health (ORH), Veterans Rural Health Resource Center - Iowa City, Iowa City VA Healthcare System, Iowa City, Iowa.

Background: Telehospitalist services are an innovative alternative approach to address staffing issues in rural and small hospitals.

Objective: To determine clinical outcomes and staff and patient satisfaction with a novel telehospitalist program among Veterans Health Administration (VHA) hospitals.

Design, Setting, And Participants: We conducted a mixed-methods evaluation of a quality improvement program with pre- and postimplementation measures. The hub site was a tertiary (high-complexity) VHA hospital, and the spoke site was a 10-bed inpatient medical unit at a rural (low-complexity) VHA hospital. All patients admitted during the study period were assigned to the spoke site.

Intervention: Real-time videoconferencing was used to connect a remote hospitalist physician with an on-site advanced practice provider and patients. Encounters were documented in the electronic health record.

Main Outcomes: Process measures included workload, patient encounters, and daily census. Outcome measures included length of stay (LOS), readmission rate, mortality, and satisfaction of providers, staff, and patients. Surveys measured satisfaction. Qualitative analysis included unstructured and semi-structured interviews with spoke-site staff.

Results: Telehospitalist program implementation led to a significant reduction in LOS (3.0 [SD, 0.7] days vs 2.3 [SD, 0.3] days). The readmission rate was slightly higher in the telehospitalist group, with no change in mortality rate. Satisfaction among teleproviders was very high. Hub staff perceived the service as valuable, though satisfaction with the program was mixed. Technology and communication challenges were identified, but patient satisfaction remained mostly unchanged.

Conclusion: Telehospitalist programs are a feasible and safe way to provide inpatient coverage and address rural hospital staffing needs. Ensuring adequate technological quality and addressing staff concerns in a timely manner can enhance program performance.
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http://dx.doi.org/10.12788/jhm.3570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929612PMC
March 2021

Spatial and temporal village-level prevalence of Plasmodium infection and associated risk factors in two districts of Meghalaya, India.

Malar J 2021 Feb 4;20(1):70. Epub 2021 Feb 4.

Indian Institute of Public Health-Shillong, Shillong, Meghalaya, 793001, India.

Background: Despite declining incidence over the past decade, malaria remains an important health burden in India. This study aimed to assess the village-level temporal patterns of Plasmodium infection in two districts of the north-eastern state of Meghalaya and evaluate risk factors that might explain these patterns.

Methods: Primary Health Centre passive malaria case data from 2014 to 2018 were analysed to characterize village-specific annual incidence and temporal trends. Active malaria case detection was undertaken in 2018 and 2019 to detect Plasmodium infections using PCR. A questionnaire collected socio-demographic, environmental, and behavioural data, and households were spatially mapped via GPS. Adult mosquitoes were sampled at a subset of subjects' houses, and Anopheles were identified by PCR and sequencing. Risk factors for Plasmodium infection were evaluated using bivariate and multivariate logistic regression analysis, and spatial cluster analysis was undertaken.

Results: The annual malaria incidence from PHC-based passive surveillance datasets in 2014-2018 was heterogenous but declining across villages in both districts. Active surveillance in 2018 enrolled 1468 individuals from 468 households (West Jaintia Hills) and 1274 individuals from 359 households (West Khasi Hills). Plasmodium falciparum prevalence per 100 people varied from 0 to 4.1% in the nine villages of West Jaintia Hills, and from 0 to 10.6% in the 12 villages of West Khasi Hills. Significant clustering of P. falciparum infections [observed = 11, expected = 2.15, Relative Risk (RR) = 12.65; p < 0.001] was observed in West Khasi Hills. A total of 13 Anopheles species were found at 53 houses in five villages, with Anopheles jeyporiensis being the most abundant. Risk of infection increased with presence of mosquitoes and electricity in the households [Odds Ratio (OR) = 1.19 and 1.11], respectively. Households with reported animals had reduced infection risk (OR = 0.91).

Conclusion: Malaria incidence during 2014-2018 declined in all study villages covered by the passive surveillance data, a period that includes the first widespread insecticide-treated net campaign. The survey data from 2018 revealed a significant association between Plasmodium infection and certain household characteristics. Since species of Plasmodium-competent mosquito vectors continue to be abundant, malaria resurgence remains a threat, and control efforts should continue.
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http://dx.doi.org/10.1186/s12936-021-03600-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859895PMC
February 2021

Small RNAs Are Implicated in Regulation of Gene and Transposable Element Expression in the Protist Trichomonas vaginalis.

mSphere 2021 01 6;6(1). Epub 2021 Jan 6.

Center for Genomics and Systems Biology, Department of Biology, New York University, New York, New York, USA

is the causative agent of trichomoniasis, the most prevalent nonviral sexually transmitted infection worldwide. Repetitive elements, including transposable elements (TEs) and virally derived repeats, comprise more than half of the ∼160-Mb genome. An intriguing question is how the parasite controls its potentially lethal complement of mobile elements, which can disrupt transcription of protein-coding genes and genome functions. In this study, we generated high-throughput RNA sequencing (RNA-Seq) and small RNA-Seq data sets in triplicate for the G3 reference strain and characterized the mRNA and small RNA populations and their mapping patterns along all six chromosomes. Mapping the RNA-Seq transcripts to the genome revealed that the majority of genes predicted within repetitive elements are not expressed. Interestingly, we identified a novel species of small RNA that maps bidirectionally along the chromosomes and is correlated with reduced protein-coding gene expression and reduced RNA-Seq coverage in repetitive elements. This novel small RNA family may play a regulatory role in gene and repetitive element expression. Our results identify a possible small RNA pathway mechanism by which the parasite regulates expression of genes and TEs and raise intriguing questions as to the role repeats may play in shaping genome evolution and the diversity of small RNA pathways in general. Trichomoniasis, caused by the protozoan , is the most common nonviral sexually transmitted infection in humans. The millions of cases each year have sequelae that may include complications during pregnancy and increased risk of HIV infection. Given its evident success in this niche, it is paradoxical that harbors in its genome thousands of transposable elements that have the potential to be extremely detrimental to normal genomic function. In many organisms, transposon expression is regulated by the activity of endogenously expressed short (∼21 to 35 nucleotides [nt]) small RNA molecules that effect gene silencing by targeting mRNAs for degradation or by recruiting epigenetic silencing machinery to locations in the genome. Our research has identified small RNA molecules correlated with reduced expression of genes and transposons. This suggests that a small RNA pathway is a major contributor to gene expression patterns in the parasite and opens up new avenues for investigation into small RNA biogenesis, function, and diversity.
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http://dx.doi.org/10.1128/mSphere.01061-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845603PMC
January 2021

Brain Magnetic Resonance Imaging Reveals Different Courses of Disease in Pediatric and Adult Cerebral Malaria.

Clin Infect Dis 2020 Dec 16. Epub 2020 Dec 16.

Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Cerebral malaria is a common presentation of severe Plasmodium falciparum infection and remains an important cause of death in the tropics. Key aspects of its pathogenesis are still incompletely understood, but severe brain swelling identified by magnetic resonance imaging (MRI) was associated with a fatal outcome in African children. In contrast, neuroimaging investigations failed to identify cerebral features associated with fatality in Asian adults.

Methods: Quantitative MRI with brain volume assessment and apparent diffusion coefficient (ADC) histogram analyses were performed for the first time in 65 patients with cerebral malaria to compare disease signatures between children and adults from the same cohort, as well as between fatal and nonfatal cases.

Results: We found an age-dependent decrease in brain swelling during acute cerebral malaria, and brain volumes did not differ between fatal and nonfatal cases across both age groups. In nonfatal disease, reversible, hypoxia-induced cytotoxic edema occurred predominantly in the white matter in children, and in the basal ganglia in adults. In fatal cases, quantitative ADC histogram analyses also demonstrated different end-stage patterns between adults and children: Severe hypoxia, evidenced by global ADC decrease and elevated plasma levels of lipocalin-2 and microRNA-150, was associated with a fatal outcome in adults. In fatal pediatric disease, our results corroborate an increase in brain volume, leading to augmented cerebral pressure, brainstem herniation, and death.

Conclusions: Our findings suggest distinct pathogenic patterns in pediatric and adult cerebral malaria with a stronger cytotoxic component in adults, supporting the development of age-specific adjunct therapies.
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http://dx.doi.org/10.1093/cid/ciaa1647DOI Listing
December 2020

Malaria in Sundargarh district, Odisha, India: Epidemiological and behavioral aspects from surveys.

Acta Trop 2020 Nov 28;211:105647. Epub 2020 Jul 28.

Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY 10003, USA. Electronic address:

To characterize malaria and assist in prevention efforts, we conducted a series of epidemiological studies in Sundargarh district, India, as part of an NIH-funded International Center of Excellence for Malaria Research. In a published survey around Rourkela in 2013-2014 (N = 1307), malaria prevalence was found to be 8.3%. Using these data, villages were divided into low (<2%), medium (2-10%) and high (>10%) malaria prevalence, and risk factors assessed by type of village. In the six low malaria villages, four persons were positive by PCR; in the four medium malaria villages, prevalence was 7% (35 infections, 7 P. vivax); and in the three high malaria villages, prevalence was 21% (62 infections, 10 P. vivax and 5 mixed with P. vivax and P. falciparum). A total of 30.6% infections were submicroscopic and 40.6% were asymptomatic. Our analyses showed that the rainy season and male gender were risk factors for malaria; in high malaria villages, young age was an additional risk factor, and indoor and outdoor spraying was protective compared to no spraying. We undertook a subsequent behavioral survey in four of the medium and high malaria villages in 2017 to investigate the behavioral aspects of malaria risk. Among 500 participants in 237 households, adult men (15+ years) were more likely to be outside in the evening (34.5% vs. 7.9% among adult women 15+ years and 0.7% among children, p < 0.001), or to sleep outside (7.5% vs. 0.5% and 0%, respectively, p < 0.001). Although women were more likely to get up before 6 a.m. (86.6%, vs. 70.5% among men, 50.7% among children, p < 0.001), men were more likely to be outside in the early morning (77.6% among men, 11.2% among women, and 11.1% among children, p < 0.001). More children used insecticide treated nets the previous night (73.4%) than men (45.6%) or women (39.6%), and repellents were used by 29.5% of 234 households (insecticide creams were not used at all). Malaria control and elimination in India will need local approaches, and the promotion of repellent cream use by at-risk groups could be further explored in addition to mass-screen or treat programs in high-risk villages.
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http://dx.doi.org/10.1016/j.actatropica.2020.105647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494530PMC
November 2020

Revisiting the Resolution of Chiari Malformation in Nonsyndromic Craniosynostosis: A Case of Posterior Cranial Vault Reconstruction in Secondary Pan-Suture Synostosis.

World Neurosurg 2020 11 27;143:158-162. Epub 2020 Jul 27.

Department of Neurosurgery, Rhode Island Hospital, The Warren Alpert School of Medicine, Brown University, Rhode Island, USA. Electronic address:

Background: While commonly seen in syndromic craniosynostosis, the incidence of Chiari malformation (CM) in nonsyndromic craniosynostosis has been reported at 5% and there is a lack of understanding of the pathophysiology and management of CM in this patient population.

Case Description: We present a 5-year-old male patient who underwent a sagittal craniosynostosis repair at the age of 5 months and returned at the age of 5 years with daily headaches associated with behavioral changes. He was found to have pan-synostoses and radiographic evidence of increased intracranial pressure, including a Chiari malformation. Neurologic and genetic workup was unremarkable. A cranial vault reconstruction was performed, and subsequent imaging demonstrated resolution of previously noted Chiari malformation.

Conclusions: In our case, we provided a unique window into the underlying pathophysiology for CM in patients with concurrent nonsyndromic craniosynostosis that we hope will add to the current foundation of literature supporting the intricate relation between cranial vault compliance and Chiari malformation or hindbrain herniation. Furthermore, we provide insight into the management of acquired CM and support isolated cranial vault reconstruction in those who do not appear to have symptomatic suboccipital compression.
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http://dx.doi.org/10.1016/j.wneu.2020.07.138DOI Listing
November 2020

Defining symptoms of malaria in India in an era of asymptomatic infections.

Malar J 2020 Jul 6;19(1):237. Epub 2020 Jul 6.

Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, 10003, USA.

Background: Malaria is a major public health problem in India. Data from surveys totaling 3031 participants at three sites revealed a high proportion of asymptomatic infections, complicating diagnosis. The aim of this study was to identify differences in complaints and symptoms between sites, and factors associated with asymptomatic Plasmodium infections.

Methods: Published data from community-based cross-sectional studies conducted between 2012 and 2015 in Nadiad (Gujarat), Chennai (Tamil Nadu), and Rourkela (Odisha) as part of the Center for the Study of Complex Malaria in India were analysed. Complaints and symptoms were systematically recorded, and Plasmodium infections confirmed using microscopy, rapid diagnostic tests (RDTs), and polymerase chain reaction (PCR). Multivariate analyses were conducted to determine the association between general symptoms and age, season, or gender, and factors associated with asymptomatic Plasmodium infections were assessed.

Results: Complaints of any illness were lowest in Chennai (17.7%), 30.6% in Rourkela and 42.7% in Nadiad. Complaints were more often reported for children; gender differences were noted in Rourkela only. In Nadiad, 7.0% of 796 participants were positive for malaria by PCR (32% Plasmodium falciparum); 78.6% had a history of fever or documented fever, 14.3% had other symptoms, and 7.1% were "truly asymptomatic". For Chennai this was 29.2%, 4.2% and 66.7% respectively, with a malaria prevalence of 2.6% by PCR of 928 participants (29% P. falciparum). In Rourkela, with 7.7% of 1307 participants positive for malaria by PCR (82% P. falciparum), the percentages were 35.6%, 24.8% and 39.6%, respectively. In Rourkela, asymptomatic infections were associated with young age and male gender (microscopy or RDT), and with rainy season (PCR). In the same site, participants with Plasmodium vivax were more likely to be asymptomatic (11/18 or 61.1%) than persons with P. falciparum mono-infections (27/78 or 34.6%); gametocytes for P. falciparum were evenly distributed between symptomatic and asymptomatic infections (2/53 vs. 2/49, respectively). The addition of the symptoms "headache", "aches" and "chills" to fever improved the case-definition of symptomatic malaria.

Conclusion: There were considerable differences in complaints at the three sites in India. Malaria and asymptomatic infections differ by region, indicating that malaria elimination will require localized approaches.
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http://dx.doi.org/10.1186/s12936-020-03310-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339403PMC
July 2020

Clinical and epidemiological characterization of severe malaria in Gujarat, India.

Virulence 2020 01;11(1):730-738

Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London, UK.

The mounting evidence supporting the capacity of to cause severe disease has prompted the need for a better characterization of the resulting clinical complications. India is making progress with reducing malaria, but epidemics of severe vivax malaria in Gujarat, one of the main contributors to the vivax malaria burden in the country, have been reported recently and may be the result of a decrease in transmission and immune development. Over a period of one year, we enrolled severe malaria patients admitted at the Civil Hospital in Ahmedabad, the largest city in Gujarat, to investigate the morbidity of severe vivax malaria compared to severe falciparum malaria. Patients were submitted to standard thorough clinical and laboratory investigations and only PCR-confirmed infections were selected for the present study. Severevivax malaria (30 patients) was more frequent than severe falciparum malaria (8 patients) in our setting, and it predominantly affected adults (median age 32 years, interquartile range 22.5 years). This suggests a potential age shift in anti-malarial immunity, likely to result from the recent decrease in transmission across India. The clinical presentation of severe vivax patients was in line with previous reports, with jaundice as the most common complication. Our findings further support the need for epidemiological studies combining clinical characterization of severe vivax malaria and serological evaluation of exposure markers to monitor the impact of elimination programmes.
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http://dx.doi.org/10.1080/21505594.2020.1773107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549892PMC
January 2020

The burden of submicroscopic and asymptomatic malaria in India revealed from epidemiology studies at three varied transmission sites in India.

Sci Rep 2019 11 19;9(1):17095. Epub 2019 Nov 19.

Indian Council of Medical Research - National Institute of Malaria Research Field Unit, Civil Hospital, Nadiad, Gujarat, India.

Malaria in India, while decreasing, remains a serious public health problem, and the contribution of submicroscopic and asymptomatic infections to its persistence is poorly understood. We conducted community surveys and clinic studies at three sites in India differing in their eco-epidemiologies: Chennai (Tamil Nadu), Nadiad (Gujarat), and Rourkela (Odisha), during 2012-2015. A total of 6,645 subject blood samples were collected for Plasmodium diagnosis by microscopy and PCR, and an extensive clinical questionnaire completed. Malaria prevalence ranged from 3-8% by PCR in community surveys (24 infections in Chennai, 56 in Nadiad, 101 in Rourkela), with Plasmodium vivax dominating in Chennai (70.8%) and Nadiad (67.9%), and Plasmodium falciparum in Rourkela (77.3%). A proportional high burden of asymptomatic and submicroscopic infections was detected in community surveys in Chennai (71% and 71%, respectively, 17 infections for both) and Rourkela (64% and 31%, 65 and 31 infections, respectively). In clinic studies, a proportional high burden of infections was identified as submicroscopic in Rourkela (45%, 42 infections) and Chennai (19%, 42 infections). In the community surveys, anemia and fever were significantly more common among microscopic than submicroscopic infections. Exploratory spatial analysis identified a number of potential malaria hotspots at all three sites. There is a considerable burden of submicroscopic and asymptomatic malaria in malarious regions in India, which may act as a reservoir with implications for malaria elimination strategies.
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http://dx.doi.org/10.1038/s41598-019-53386-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863831PMC
November 2019

Relationship Between Single Tablet Antiretroviral Regimen and Adherence to Antiretroviral and Non-Antiretroviral Medications Among Veterans' Affairs Patients with Human Immunodeficiency Virus.

AIDS Patient Care STDS 2017 09 3;31(9):370-376. Epub 2017 Aug 3.

1 Department of Pharmacy Practice, Albany College of Pharmacy & Health Sciences , Albany, New York.

Several antiretrovirals (ART) have been coformulated as single tablet regimens (STR). Study objectives were to compare ART and non-ART adherence between STR and multiple tablet regimens (MTR) recipients, determine whether STR independently predicts ART adherence, and determine whether ART adherence influences non-ART adherence. A retrospective cohort study was performed among Upstate New York Veterans' Healthcare Administration (VISN-2) patients from 2000 to 2013. Inclusion criteria were age ≥18 years, human immunodeficiency virus (HIV) infection, receipt of ≥3 ART medications for ≥3 months, and available pharmacy refill records. The two study outcomes were adherence to ART medications and non-ART medications. Adherence was determined with pharmacy refill records that were used to calculate medication possession ratios. Among the 1202 subjects, there were 165 (13.7%) STR and 1037 (86.3%) MTR recipients. Mean ± standard deviation (SD) ART adherence was significantly higher for STR recipients (81.5% ± 15.3%) than MTR recipients (66.1% ± 21.1%), p < 0.001. Use of STR [adjusted odds ratio (aOR): 5.76, 95% confidence interval (CI): 3.84-8.65, p < 0.001] was independently associated with optimal (≥90%) adherence to ART. Mean ± SD non-ART adherence did not differ between STR (78.8% ± 15.6%) and MTR recipients (80.8% ± 16.0%), p = 0.17. Optimal adherence to ART medications (aOR: 2.30, 95% CI: 1.57-3.38, p < 0.001) was independently associated with optimal adherence to non-ART medications. The use of STRs are associated with optimal adherence to ART medications, but not directly associated with adherence to non-ART medications.
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http://dx.doi.org/10.1089/apc.2017.0081DOI Listing
September 2017

Genetic Indicators of Drug Resistance in the Highly Repetitive Genome of Trichomonas vaginalis.

Genome Biol Evol 2017 06;9(6):1658-1672

Department of Biology, Center for Genomics and Systems Biology, New York University, New York.

Trichomonas vaginalis, the most common nonviral sexually transmitted parasite, causes ∼283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance. Reduced representation genome sequencing of ∼100 T. vaginalis clinical isolates identified 3,923 SNP markers and presence of a bipartite population structure. Linkage disequilibrium was found to decay rapidly, suggesting genome-wide recombination and the feasibility of genetic association studies in the parasite. We identified 72 SNPs associated with metronidazole resistance, and a comparison of SNPs within several lab-derived resistant lines revealed an overlap with the clinically resistant isolates. We identified SNPs in genes for which no function has yet been assigned, as well as in functionally-characterized genes relevant to drug resistance (e.g., pyruvate:ferredoxin oxidoreductase). Transcription profiles of resistant strains showed common changes in genes involved in drug activation (e.g., flavin reductase), accumulation (e.g., multidrug resistance pump), and detoxification (e.g., nitroreductase). Finally, we identified convergent genetic changes in lab-derived resistant lines of Tritrichomonas foetus, a distantly related species that causes venereal disease in cattle. Shared genetic changes within and between T. vaginalis and Tr. foetus parasites suggest conservation of the pathways through which adaptation has occurred. These findings extend our knowledge of drug resistance in the parasite, providing a panel of markers that can be used as a diagnostic tool.
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http://dx.doi.org/10.1093/gbe/evx110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522705PMC
June 2017

Minimally Invasive Approach for Resection of Parameningeal Rhabdomyosarcoma.

J Neurol Surg B Skull Base 2017 Jun 12;78(3):210-214. Epub 2016 Dec 12.

Department of Otolaryngology - Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan, United States.

 About one-third of rhabdomyosarcomas arise in the head and neck, with parameningeal primaries accounting for half of these. Principles of management involve chemotherapy, radiation, or both, in addition to surgical biopsy, debulking, and complete or near-complete resection. In the head and neck, diagnostic biopsies have historically been performed without attempt at resection due to proximity to critical structures and cosmetic considerations.  Retrospective chart review of three cases of rhabdomyosarcoma at the cranial base managed through minimally invasive endoscopic surgical resection and adjuvant therapy.  Three patients were identified as having undergone endoscopic surgical debulking or margin-negative resection of a rhabdomyosarcoma of the cranial base. Two of three patients had complete resection based on intraoperative margin control. All three patients underwent adjuvant therapy within 1 month of diagnosis. Follow-up time ranged from 5 months to 3 years with all patients disease-free at last follow-up.  Skull base surgeons should routinely be involved in multidisciplinary treatment planning for parameningeal rhabdomyosarcomas, as surgical options have evolved to allow for potential endoscopic resection with low morbidity and no or minimal delay in additional treatment options.
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http://dx.doi.org/10.1055/s-0036-1597279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461162PMC
June 2017

Filthy lucre: A metagenomic pilot study of microbes found on circulating currency in New York City.

PLoS One 2017 6;12(4):e0175527. Epub 2017 Apr 6.

Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America.

Background: Paper currency by its very nature is frequently transferred from one person to another and represents an important medium for human contact with-and potential exchange of-microbes. In this pilot study, we swabbed circulating $1 bills obtained from a New York City bank in February (Winter) and June (Summer) 2013 and used shotgun metagenomic sequencing to profile the communities found on their surface. Using basic culture conditions, we also tested whether viable microbes could be recovered from bills.

Results: Shotgun metagenomics identified eukaryotes as the most abundant sequences on money, followed by bacteria, viruses and archaea. Eukaryotic assemblages were dominated by human, other metazoan and fungal taxa. The currency investigated harbored a diverse microbial population that was dominated by human skin and oral commensals, including Propionibacterium acnes, Staphylococcus epidermidis and Micrococcus luteus. Other taxa detected not associated with humans included Lactococcus lactis and Streptococcus thermophilus, microbes typically associated with dairy production and fermentation. Culturing results indicated that viable microbes can be isolated from paper currency.

Conclusions: We conducted the first metagenomic characterization of the surface of paper money in the United States, establishing a baseline for microbes found on $1 bills circulating in New York City. Our results suggest that money amalgamates DNA from sources inhabiting the human microbiome, food, and other environmental inputs, some of which can be recovered as viable organisms. These monetary communities may be maintained through contact with human skin, and DNA obtained from money may provide a record of human behavior and health. Understanding these microbial profiles is especially relevant to public health as money could potentially mediate interpersonal transfer of microbes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175527PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383295PMC
September 2017

A Feast of Malaria Parasite Genomes.

Cell Host Microbe 2017 03;21(3):310-312

Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY 10003, USA.

The Plasmodium genus has evolved over time and across hosts, complexifying our understanding of malaria. In a recent Nature paper, Rutledge et al. (2017) describe the genome sequences of three major human malaria parasite species, providing insight into Plasmodium evolution and raising the question of how many species there are.
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http://dx.doi.org/10.1016/j.chom.2017.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820760PMC
March 2017

The use of mosquito repellents at three sites in India with declining malaria transmission: surveys in the community and clinic.

Parasit Vectors 2016 07 27;9(1):418. Epub 2016 Jul 27.

National Institute of Malaria Research, Indian Council of Medical Research, Dwarka Sector 8, New Delhi, India.

Background: Repellents such as coils, vaporizers, mats and creams can be used to reduce the risk of malaria and other infectious diseases. Although evidence for their effectiveness is limited, they are advertised as providing an additional approach to mosquito control in combination with other strategies, e.g. insecticide-treated nets. We examined the use of repellents in India in an urban setting in Chennai (mainly Plasmodium vivax malaria), a peri-urban setting in Nadiad (both P. vivax and P. falciparum malaria), and a more rural setting in Raurkela (mainly P. falciparum malaria).

Methods: The use of repellents was examined at the household level during a census, and at the individual level in cross-sectional surveys and among patients visiting a clinic with fever or other symptoms. Factors associated with their use were examined in a multivariate analysis, and the association between malaria and the use of repellents was assessed among survey- and clinic participants.

Results: Characteristics of participants differed by region, with more people of higher education present in Chennai. Use of repellents varied between 56-77 % at the household level and between 32-78 % at the individual level. Vaporizers were the main repellents used in Chennai, whereas coils were more common in Nadiad and Raurkela. In Chennai and Nadiad, vaporizers were more likely to be used in households with young male children. Vaporizer use was associated with higher socio-economic status (SES) in households in Chennai and Nadiad, whereas use of coils was greater in the lower SES strata. In Raurkela, there was a higher use of coils among the higher SES strata. Education was associated with the use of a repellent among survey participants in Chennai and clinic study participants in Chennai and Nadiad. Repellent use was associated with less malaria in the clinic study in Chennai and Raurkela, but not in the surveys, with the exception of the use of coils in Nadiad.

Conclusions: Repellents are widely used in India. Their use is influenced by the level of education and SES. Information on effectiveness and guidance on choices may improve rational use.
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http://dx.doi.org/10.1186/s13071-016-1709-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963934PMC
July 2016

Why segment the maxilla between laterals and canines?

Dental Press J Orthod 2016 Jan-Feb;21(1):110-25

Center for Dentofacial Deformity, Hospital Santa Casa de Misericórdia, Salvador, Bahia, Brazil.

Introduction: Maxillary surgery on a bone segment enables movement in the sagittal and vertical planes. When performed on multiple segments, it further provides movement in the transverse plane. Typical sites for interdental osteotomies are between laterals and canines, premolars and canines, or between incisors. Additionally, osteotomies can be bilateral, unilateral or asymmetric. The ability to control intercanine width, buccolingual angulation of incisors, and correct Bolton discrepancy are some of the advantages of maxillary segmentation between laterals and canines.

Objective: This article describes important features to be considered in making a clinical decision to segment the maxilla between laterals and canines when treating a dentoskeletal deformity. It further discusses the history of this surgical approach, the indications for its clinical use, the technique used to implement it, as well as its advantages, disadvantages, complications and stability. It is therefore hoped that this paper will contribute to disseminate information on this topic, which will inform the decision-making process of those professionals who wish to make use of this procedure in their clinical practice.

Conclusions: Segmental maxillary osteotomy between laterals and canines is a versatile technique with several indications. Furthermore, it offers a host of advantages compared with single-piece osteotomy, or between canines and premolars.
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http://dx.doi.org/10.1590/2177-6709.21.1.110-125.sarDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816593PMC
September 2017

Characterizing the genetic diversity of the monkey malaria parasite Plasmodium cynomolgi.

Infect Genet Evol 2016 06 14;40:243-252. Epub 2016 Mar 14.

Center for Genomics and Systems Biology, Department of Biology, New York University, 12 Waverly Place, New York, NY 10003, United States. Electronic address:

Plasmodium cynomolgi is a malaria parasite that typically infects Asian macaque monkeys, and humans on rare occasions. P. cynomolgi serves as a model system for the human malaria parasite Plasmodium vivax, with which it shares such important biological characteristics as formation of a dormant liver stage and a preference to invade reticulocytes. While genomes of three P. cynomolgi strains have been sequenced, genetic diversity of P. cynomolgi has not been widely investigated. To address this we developed the first panel of P. cynomolgi microsatellite markers to genotype eleven P. cynomolgi laboratory strains and 18 field isolates from Sarawak, Malaysian Borneo. We found diverse genotypes among most of the laboratory strains, though two nominally different strains were found to be genetically identical. We also investigated sequence polymorphism in two erythrocyte invasion gene families, the reticulocyte binding protein and Duffy binding protein genes, in these strains. We also observed copy number variation in rbp genes.
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http://dx.doi.org/10.1016/j.meegid.2016.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844884PMC
June 2016

What is the value of reactive case detection in malaria control? A case-study in India and a systematic review.

Malar J 2016 Feb 6;15:67. Epub 2016 Feb 6.

National Institute of Malaria Research Field Unit, Indian Council of Medical Research, National Institute of Epidemiology Campus, Ayapakkam, Chennai, Tamil Nadu, India.

Background: Reactive case detection (RCD) for malaria is a strategy to identify additional malaria infections in areas of low malaria transmission and can complement passive surveillance. This study describes experiences with RCD in two Indian sites, and aimed to synthesize experiences with RCD across endemic countries.

Methods: RCD programmes were piloted in two urban areas of India with a low prevalence of mainly Plasmodium vivax malaria in 2014. Cases were identified in a clinic by microscopy and contacts were screened within 2 weeks; PCR, in addition to microscopy, was used to detect Plasmodium parasites. A systematic review was conducted to identify RCD experiences in the literature.

Results: In Chennai, 868 contacts were enrolled for 18 index cases of clinical malaria; in Nadiad, 131 contacts were enrolled for 20 index cases. No new malaria infections were detected in Nadiad among contacts, and four new infections were detected in Chennai (three P. vivax and one Plasmodium falciparum), of which two were among household members of index cases. An additional five studies describing results from an RCD strategy were identified in the literature: four in Africa and one in Thailand. Including the results from India, the average number of contacts screened per index case in a total of seven studies ranged from four to 50, and 126 in a case study in Thailand with one index case. Malaria was detected in 0-45 % of the contacted persons. The average number of index cases needed to be traced to find one new case of malaria ranged from one to five, and could not be assessed in one study in India (no contacts positive for 20 cases). Sharing the household with an index case was associated with a five-fold increased risk of malaria compared to contacts from households without an index case (pooled risk ratio 5.29, 95 % CI 3.31-8.47, I(2) 0 %, four studies).

Conclusions: RCD in areas of low malaria transmission is a labour-intensive strategy, and its benefit is not clear. Studies are needed to assess how RCD can be optimized or into alternatives where interventions are targeted to family members or hotspots.
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http://dx.doi.org/10.1186/s12936-016-1120-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744450PMC
February 2016

Techniques in Orthognathic Surgery.

Atlas Oral Maxillofac Surg Clin North Am 2016 Mar;24(1):ix

Department of Oral and Maxillofacial Surgery, University of Oklahoma, College of Dentistry, 1201 North Stonewall, Oklahoma City, OK 73104, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cxom.2015.12.001DOI Listing
March 2016

Le Fort I Osteotomy.

Atlas Oral Maxillofac Surg Clin North Am 2016 Mar 17;24(1):1-13. Epub 2015 Dec 17.

Department of Oral and Maxillofacial Surgery, University of Oklahoma College of Dentistry, 1201 North Stonewall, Oklahoma City, OK 73117, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cxom.2015.10.001DOI Listing
March 2016

Authors' response.

Am J Orthod Dentofacial Orthop 2015 Oct;148(4):528-9

Oklahoma City, Okla.

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http://dx.doi.org/10.1016/j.ajodo.2015.07.018DOI Listing
October 2015

A Framework for Global Collaborative Data Management for Malaria Research.

Am J Trop Med Hyg 2015 Sep 10;93(3 Suppl):124-132. Epub 2015 Aug 10.

Data generated during the course of research activities carried out by the International Centers of Excellence for Malaria Research (ICEMR) is heterogeneous, large, and multi-scaled. The complexity of federated and global data operations and the diverse uses planned for the data pose tremendous challenges and opportunities for collaborative research. In this article, we present the foundational principles for data management across the ICEMR Program, the logistics associated with multiple aspects of the data life cycle, and describe a pilot centralized web information system created in PlasmoDB to query a subset of this data. The paradigm proposed as a solution for the data operations in the ICEMR Program is widely applicable to large, multifaceted research projects, and could be reproduced in other contexts that require sophisticated data management.
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http://dx.doi.org/10.4269/ajtmh.15-0003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574270PMC
September 2015

Postsurgical volumetric airway changes in 2-jaw orthognathic surgery patients.

Am J Orthod Dentofacial Orthop 2015 May;147(5):536-46

Assistant professor, Department of Biostatistics and Epidemiology, University of Oklahoma, Oklahoma City, Okla.

Introduction: Findings from early cephalometric studies on airway changes after 2-jaw orthognathic surgery have been challenged because the previous anteroposterior interpretation of airway changes can now be evaluated in 3 dimensions. The aims of this study were to use cone-beam computed tomography to quantify the nasopharynx, oropharynx, and total airway volume changes associated with skeletal movements of the maxilla and mandible in a sample of patients undergoing 2-jaw orthognathic surgery for correction of skeletal malocclusion.

Methods: Skeletal movements and airway volumes of 71 postpubertal patients (31 male, 40 female; mean age, 18.8 years) were measured. They were divided into 2 groups based on ANB angle, overjet, and occlusion (Class II: ANB, >2°; overjet, >1 mm; total, 35 subjects; and Class III: ANB, <1°; overjet, <1 mm; total, 36 subjects). Presurgical and postsurgical measurements were collected for horizontal, vertical, and transverse movements of the maxilla and the mandible, along with changes in the nasopharynx, oropharynx, and total airways. Associations between the directional movements of skeletal structures and the regional changes in airway volume were quantified. Changes in the most constricted area were also noted.

Results: Horizontal movements of D-point were significantly associated with increases in both total airway (403.6 ± 138.6 mm(3); P <0.01) and oropharynx (383.9 ± 127.9 mm(3); P <0.01) volumes. Vertical movements of the posterior nasal spine were significantly associated with decreases in total airway volume (-459.2 ± 219.9 mm(3); P = 0.04) and oropharynx volume (-639.7 ± 195.3 mm(3); P <0.01), increases in nasopharynx (187.2 ± 47.1 mm(3); P <0.01) volume, and decreases in the most constricted area (-10.63 ± 3.69 mm(2); P <0.01). In the Class III patients only, the vertical movement of D-point was significantly associated with decreases in both total airway (-724.0 ± 284.4 mm(3); P = 0.02) and oropharynx (-648.2 ± 270.4 mm(3); P = 0.02) volumes. A similar negative association was observed for the most constricted area for the vertical movement of D-point (-15.45 ± 4.91 mm(2); P <0.01).

Conclusions: Optimal control of airway volume is through management of the mandible in the horizontal direction and the vertical movement of the posterior maxilla for all patients. The surgeon and the orthodontist should optimally plan these movements to control gains or losses in airway volume as a result of orthognathic surgery.
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http://dx.doi.org/10.1016/j.ajodo.2014.12.023DOI Listing
May 2015

The biology of Plasmodium vivax explored through genomics.

Ann N Y Acad Sci 2015 Apr 18;1342:53-61. Epub 2015 Feb 18.

Center for Genomics and Systems Biology, New York University, New York, New York.

Malaria is a mosquito-borne disease caused by the Plasmodium parasite. Of the four Plasmodium species that routinely cause human malaria, Plasmodium vivax is the most widespread species outside Africa, causing ∼18.9 million cases in 2012. P. vivax cannot be cultured continuously in vitro, which severely hampers research in nonendemic and endemic countries alike. Consequently, whole-genome sequencing has become an effective means to interrogate the biology of the P. vivax parasite. Our comparative genomic analysis of five P. vivax reference genomes and several whole-genome sequences of the closely related monkey malaria species P. cynomolgi has revealed an extraordinary level of genetic diversity and enabled characterization of novel multigene families and important single-copy genes. The generation of whole-genome sequences from multiple clinical isolates is also driving forward knowledge concerning the biology and evolution of the species. Understanding the biology of P. vivax is crucial to develop potential antimalarial drugs and vaccines and to achieve the goal of eliminating malaria.
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http://dx.doi.org/10.1111/nyas.12708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405435PMC
April 2015

Retinal NMDA receptor function and expression are altered in a mouse lacking D-amino acid oxidase.

J Neurophysiol 2013 Dec 25;110(12):2718-26. Epub 2013 Sep 25.

Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota;

D-serine is present in the vertebrate retina and serves as a coagonist for the N-methyl-D-aspartate (NMDA) receptors of ganglion cells. Although the enzyme D-amino acid oxidase (DAO) has been implicated as a pathway for d-serine degradation, its role in the retina has not been established. In this study, we investigated the role of DAO in regulating D-serine levels using a mutant mouse line deficient in DAO (ddY/DAO(-)) and compared these results with their wild-type counterparts (ddY/DAO(+)). Our results show that DAO is functionally present in the mouse retina and normally serves to reduce the background levels of D-serine. The enzymatic activity of DAO was restricted to the inner plexiform layer as determined by histochemical analysis. Using capillary electrophoresis, we showed that mutant mice had much higher levels of D-serine. Whole cell recordings from identified retinal ganglion cells demonstrated that DAO-deficient animals had light-evoked synaptic activity strongly biased toward a high NMDA-to-AMPA receptor ratio. In contrast, recordings from wild-type ganglion cells showed a more balanced ratio between the two receptor subclasses. Immunostaining for AMPA and NMDA receptors was carried out to compare the two receptor ratios by quantitative immunofluorescence. These studies revealed that the mutant mouse had a significantly higher representation of NMDA receptors compared with the wild-type controls. We conclude that 1) DAO is an important regulatory enzyme and normally functions to reduce D-serine levels in the retina, and 2) D-serine levels play a role in the expression of NMDA receptors and the NMDA-to-AMPA receptor ratio.
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http://dx.doi.org/10.1152/jn.00310.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882816PMC
December 2013

A comparison of particulate and Onyx embolization in preoperative devascularization of carotid body tumors.

Neuroradiology 2013 Sep 22;55(9):1113-8. Epub 2013 Jun 22.

Department of Radiology, University of Michigan, Ann Arbor, MI, USA.

Introduction: Preoperative embolization of a carotid body tumor (CBT) is a useful adjunct prior to surgical excision because it decreases operative blood loss and improves surgical outcomes. Traditionally, this is performed by transarterial particulate embolization (TAPE). More recently, direct percutaneous embolization (DPE) with Onyx is recognized as a promising technique for preoperative embolization. We compared these two techniques in patients treated for CBTs at our institution.

Methods: We retrospectively reviewed cases of preoperative devascularization of CBT from 1 January 1995 through 1 September 2012. Patient cases were placed into two groups: TAPE and DPE. Operative blood loss, operative length, angiographic devascularization, embolization procedure complications, operative transfusion requirements, postoperative hospital stay, intensive care unit (ICU) stay, and procedure-related mortalities were compared.

Results: A total of 17 patients underwent preoperative devascularization of their CBT with TAPE technique and ten patients using the DPE technique with Onyx. Average operative blood loss was significantly higher in the TAPE group (Mann-Whitney U test, p = 0.04). Operative time was also higher, although this difference was not significant. Two patients required intraoperative blood transfusions in the TAPE group while none required transfusions in the DPE group. There was no significant difference in ICU stay or length of hospitalization. One serious embolization procedure complication occurred in the TAPE group and none in the DPE group.

Conclusion: Operative blood loss in the DPE group was significantly less than the TAPE group. Blood transfusion requirement, operative time, and complications were less in the DPE group, although they did not reach statistical significance.
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http://dx.doi.org/10.1007/s00234-013-1220-3DOI Listing
September 2013

A comparison of particulate and onyx embolization in preoperative devascularization of juvenile nasopharyngeal angiofibromas.

Neuroradiology 2013 Sep 9;55(9):1089-96. Epub 2013 Jun 9.

Medical School, University of Michigan, Ann Arbor, MI, USA.

Introduction: Juvenile nasopharyngeal angiofibromas (JNAs) are hypervascular tumors that may benefit from preoperative devascularization to reduce intraoperative blood loss (IBL). The purpose of this study was to compare transarterial particulate embolization (TAPE) with the direct percutaneous embolization (DPE) technique using ethylene vinyl alcohol (Onyx, ev3, Irvine, CA) for the preoperative devascularization of a JNA.

Methods: We retrospectively reviewed 50 consecutive JNA resections since 1995 for which preoperative embolization was either transarterial with particulate material (n = 39) or DPE (n = 11) using only Onyx. The IBL, transfusion requirements, operative time, and length of hospital admission were compared between the two groups.

Results: The mean IBL was 1,348.7 ± 932.2 mL particulate group, 569.1 ± 700.7 mL Onyx group (one-tailed Student's t test p = 0.003). The mean unit of packed red blood cells was 1.56 ± 2.01 units particulate group, 0.45 ± 1.04 units Onyx group (p = 0.009). The relationship between embolization type and IBL remained significant or strongly correlated when accounting for the Fisch stage of the tumor (p = 0.010 and p = 0.056, respectively, by a multivariate least squares fit; alternately p = 0.0003 and p = 0.023, respectively, in the subset of patients with Fisch stage III tumors only). We also found that the proportion of resections for which an endoscopic approach could be used was significantly higher in the Onyx group than the particulate group (81.8 and 18.2 %; Pearson p = 0.0002), and this was also significant both in our multivariate nominal logistic fit (p < 0.001) and in the subset of patients with Fisch stage III tumors (p = 0.018).

Conclusion: Pre-operative DPE with Onyx of a JNA when compared to TAPE significantly decreased IBL and RBC transfusion requirement during surgical resection. The proportion of surgical resections performed from an endoscopic approach was higher in the DPE Onyx group, which may have affected the results.
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http://dx.doi.org/10.1007/s00234-013-1213-2DOI Listing
September 2013

Pituitary carcinoma with endolymphatic sac metastasis.

Pituitary 2014 Jun;17(3):210-3

Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.

Pituitary carcinoma is characterized by the presence of a metastatic lesion(s) in a location non-contiguous with the original pituitary tumor. The mechanism(s) of malignant transformation are not known. A 15 year-old male was diagnosed in 1982 with a pituitary macroadenoma and acromegaly (random GH 67 ng/ml and no suppression by oral glucose). His prolactin was normal between 18 and 23 ng/ml. Transcranial resection in July 1983 was followed by radiation therapy. The tumor was immunopositive for GH and prolactin. The proliferation MIB-1 index was 0-1%. With aqueous Octreotide 100 mcg 4× daily both GH and IGF-1 became normal. The patient was lost to follow-up and was treated by his local physician. In 2001, his IGF-1 level was 1271 ng/ml, and his random GH was 1.8-2.4 ng/ml by ILMA despite progressive increase in the dose of Sandostatin LAR to 140 mg/month in divided doses. Prolactin remained normal or minimally increased between 15 and 25 ng/ml. In 2009 he was diagnosed with the tumor in the location of left endolymphatic sac. Histological examination showed low grade pituitary carcinoma strongly immunopositive for prolactin but negative for GH. MIB-1 antibody labeled 0-5% cells. In 2012 endoscopic resection of the pituitary tumor remnant was attempted. Immunohistochemical stains were strongly immunopositive for both prolactin and GH, similar to his original pituitary tumor. The MIB-1 proliferation index was low from 0 to 1%. To our knowledge this is the first case of pituitary carcinoma in the endolymphatic sac region. The dichotomy between the cell population of the pituitary lesion (GH/prolactin producing) and the metastasis (purely prolactin-producing) may suggest that the metastatic pituitary lesion derived from a clone distinct from the original one.
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http://dx.doi.org/10.1007/s11102-013-0489-xDOI Listing
June 2014