Medical Specialties Commons^™

Tadalafil Enhances Immune Signatures In Response To Neoadjuvant Nivolumab In Resectable Head And Neck Squamous Cell Carcinoma, Adam J. Luginbuhl, Jennifer Johnson, Larry Harshyne,, Alban J Linnenbach, Sanket Kumar Shukla, Angela Alnemri, Gaurav Kumar, David Cognetti, Joseph Curry, Nikita Kotlov, Zoya Antysheva, Sandrine Degryse, Kyle Mannion, Michael K Gibson, James Netterville, Brandee Brown, Rita S. Axelrod, Ralph G. Zinner, Madalina Tuluc, Stacey Gargano, Benjamin E Leiby, Ayako Shimada, M G Mahoney, Ubaldo E. Martinez-Outshoorn, Ulrich Rodeck, Young J Kim, Andrew P. South, Athanassios Argiris

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Purpose: We hypothesize that the addition of the phosphodiesterase-5 inhibitor tadalafil to the PD-1 inhibitor nivolumab, is safe and will augment immune-mediated antitumor responses in previously untreated squamous cell carcinoma of the head and neck (HNSCC).

Patients and methods: We conducted a two-arm multi-institutional neoadjuvant randomized trial in any-stage resectable HNSCC (NCT03238365). Patients were stratified at randomization by human papillomavirus (HPV) status. Patients in both arms received nivolumab 240 mg intravenously on days 1 and 15 followed by surgery on day 28. Those in the combination therapy arm also received tadalafil 10 mg orally once daily for 4 weeks. Imaging, …

Penicillin Allergy Assessment And Medical Referral To Promote Antibiotic Stewardship, Elaine Bailey Pharmd, Mackenzie Connell, Marie Fluent Dds, Erinne Kennedy Dds, Mph, Mmsc

The Journal of the Michigan Dental Association

Antibiotic stewardship is an integral practice for the dental team to ensure a safe dental visit for patients. Now, with clinical practice guidelines and state toolkits, more dentists are aware of and actively practicing antibiotic stewardship. With the application of antibiotic stewardship practices, dentists are identifying the need for additional tools to enhance practice. For example, one need that has been identified is a tool for screening patients for true penicillin allergies. The Penicillin Allergy Assessment Tool (PAAT) is a decision-making tool that can be used chairside to screen patients who report an allergy to penicillin. After screening, dentists can …

Endovascular Treatment Of Acute Ischemic Stroke With The Penumbra System In Routine Practice: Complete Registry Results, Osama O. Zaidat, Johanna T. Fifi, Ashish Nanda, Benjamin Atchie, Keith Woodward, Arnd Doerfler, Alejandro Tomasello, Inder Paul Singh, Wondwossen G. Tekle, Ameer E. Hassan

School of Medicine Publications

Background and purpose: The purpose of the COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device) registry was to evaluate the generalizability of the safety and efficacy of the Penumbra System (Penumbra, Inc, Alameda) in a real-world setting.

Methods: COMPLETE was a global, prospective, postmarket, multicenter registry. Patients with large vessel occlusion-acute ischemic stroke who underwent mechanical thrombectomy using the Penumbra System with or without the 3D Revascularization Device as frontline approach were enrolled at 42 centers (29 United States, 13 Europe) from July 2018 to October 2019. Primary efficacy end points were …

Modifying Group Interpersonal Psychotherapy For Peripartum Adolescents In Sub-Saharan African Context: Reviewing Differential Contextual And Implementation Considerations, Manasi Kumar, Helen Verdeli, Shekhar Saxena, Inge Petersen, Keng Yen Huang, Caleb Othieno, Nancy Grote, Roslyn Law, Jurgen Unutzer, Mary Mckay

Brain and Mind Institute

Background: This study describes adaptation and modification of World Health Organization (WHO) recommended group interpersonal psychotherapy (IPT-G) for depressed peripartum adolescents. The adaptation process includes accommodating contextual factors and strategies to address intervention implementation barriers, such as engagement problems with adolescents, caregivers, and providers, and stigma and dearth of mental health specialists. The modifications include and adolescent relevant iterations to the therapy format and content.

Methods: A multi-stakeholder led two-stage intervention adaptation and modification process integrating mixed qualitative methods were used with pregnant and parenting adolescents, their partners, and health care workers. In-depth interviews focusing on personal, relationship, social, and …

Post Covid Anti-Nmdar Encephalitis In An Adolescent Girl, Javeria Raza Alvi, Muhammad Haider Sultan, Tipu Sultan

Pakistan Journal of Neurological Sciences (PJNS)

Anti-N-Methyl D-aspartate receptor (NMDAR) encephalitis is a neuro-inflammatory disorder caused by antibodies targeting neurons in the central nervous system. Certain viruses break immune tolerance of neuronal proteins and increase the permeability of blood brain barrier (BBB) to antibodies resulting in post infectious autoimmunity. We report a case about a 13 years old girl diagnosed as a case of anti-NMDAR encephalitis, who presented with psychiatric symptoms followed by abnormal movements and encephalopathy, with later development of autonomic instability with tachycardia and blood pressure at 98th centile. Her thyroid profile initially showed hyperthyroidism with negative anti-thyroid antibodies with subsequent normalization without anti-thyroid …

Stroke: Are Women Worse Off?, Maria Khan

Pakistan Journal of Neurological Sciences (PJNS)

Stroke is a leading cause of death and disability worldwide. Although the age standardized rates of stroke have fallen, the absolute number of strokes continue to rise, particularly in the low and middle income countries. It was long recognized that women have a lower age-standardized incidence of stroke. This understanding has been challenged by the Global burden of Disease Study 2019 which highlights that although the total number of Disability Adjusted Life Years (DALYs) from stroke were higher in males compared to females, the number of incident and prevalent strokes were higher in females. In addition, the study did not …

World Brain Day- Brain Health For All, Safa Younis

Pakistan Journal of Neurological Sciences (PJNS)

World Brain Day is celebrated annually on July 22nd, and this year’s theme was “Brain Health for All”. In honor of World Brain Day, Aga Khan University, in collaboration with the World Federation of Neurology, hosted an international webinar moderated by Dr. Shafaq Saleem. Dr. Mohammad Wasay commenced the session by discussing the importance of WHO’s adoption of the Intersectoral Global Action Plan on epilepsy and other neurological disorders. He discussed how significantly this 10-year action plan will improve neurological training, awareness, and advocacy. He explained how this webinar would unpack problems related to neurological care in different parts of …

Multiple Sclerosis Care In Pakistan; Analysis Of Data Presented At First Paktrims Conference, Zara Shah, Haris Majid, Sadia Nishat, Sumera Rafat Umer, Sundus Mehtab Shafee, Ahmed Wali, Naila Shahbaz

Pakistan Journal of Neurological Sciences (PJNS)

Novel data on Multiple Sclerosis (MS) in Pakistan from leading institutes in the country was presented at the first Pakistan Treatment in Multiple Sclerosis (PAKTRIMS) Conference, organized by the section of Neurology, department of Medicine, Aga Khan University, Karachi on Saturday, December 18, 2021. Pakistan has been considered to have a low prevalence of MS; however, recent research reveals that it is not as uncommon as previously believed to be in the country. The true prevalence and incidence of MS in the country is unknown because of dearth of research. Data of MS patients enrolled in various private and public …

Apolipoprotein E Proteinopathy Is A Major Dementia-Associated Pathologic Biomarker In Individuals With Or Without The Apoe Epsilon 4 Allele, Jozsef Gal, Yuriko Katsumata, Haining Zhu, Sukanya Srinivasan, Jing Chen, Lance Allen Johnson, Wang-Xia Wang, Lesley Renee Golden, Donna M. Wilcock, Gregory A. Jicha, Matthew D. Cykowski, Peter Tobias Nelson

Spinal Cord and Brain Injury Research Center Faculty Publications

The amygdala is vulnerable to multiple or “mixed” mis-aggregated proteins associated with neurodegenerative conditions that can manifest clinically with amnestic dementia; the amygdala region is often affected even at earliest disease stages. With the original intent of identifying novel dementiaassociated proteins, the detergent-insoluble proteome was characterized from the amygdalae of 40 participants from the University of Kentucky Alzheimer’s Disease Center autopsy cohort. These individuals encompassed a spectrum of clinical conditions (cognitively normal to severe amnestic dementia). Polypeptides from the detergent-insoluble fraction were interrogated using liquid chromatography-electrospray ionization-tandem mass spectrometry. As anticipated, portions of peptides previously associated with neurologic diseases were …

Knowledge And Awareness Regarding Uses Of Extracted Natural Tooth In Clinical Practice, Momina Anis Motiwala, Shizrah Jamal, Karshma Devi, Rabia Ghafoor

Section of Dental-Oral Maxillofacial Surgery

Restoration of aesthetics is one the major patients’ concern in dentistry which may be disrupted due to tooth-loss secondary to trauma, or as part of orthodontic treatment or periodontal problem. A number of treatment options are available for the replacement of teeth, but they may be expensive, and time-consuming, involving artificial teeth. For immediate tooth replacement, patient’s own intentionally extracted or unintentionally avulsed tooth maybe used. The current narrative review was planned to discuss various techniques for the use of natural tooth pontic, which preserves the original contours, size and colour of the replaced tooth. Before using these teeth in …

Long-Term Safety And Efficacy Of Deutetrabenazine In Younger And Older Patients With Tardive Dyskinesia, Martha Sajatovic

Faculty Scholarship

Objectives: To assess long-term safety and efficacy of deutetrabenazine in younger (<55 years) and older (≥55 years) adult participants with tardive dyskinesia (TD). Design: Three-year, single-arm, open-label extension (OLE) study enrolling participants who completed the 12-week, pivotal ARM-TD or AIM-TD studies. Setting: Seventy-six centers in the United States and Europe. Participants: A total of 337 participants with TD (119 younger and 218 older). Intervention: Deutetrabenazine was initiated at 12 mg/day and titrated once weekly by 6 mg/day using a response-driven dosing regimen until adequate dyskinesia control was reached or a clinically significant adverse event occurred. Measurements: This post hoc analysis assessed change and percent change from baseline in total motor Abnormal Involuntary Movement Scale (AIMS) score, response rates for ≥50% AIMS improvement, Clinical Global Impression of Change (CGIC), Patient Global Impression of Change (PGIC), and safety in younger and older participants with TD. Results: After 3 years of open-label treatment, mean deutetrabenazine dose was ∼39.5 mg/day in both groups. Mean±SE changes from baseline in total motor AIMS score were –6.7 ± 0.62 and –6.5 ± 0.47 in younger and older participants, respectively (percent changes: –61.4% ± 4.10% and –54.6% ± 3.01%); 76% of younger and 62% of older participants achieved ≥50% AIMS response. Most younger and older participants achieved treatment success per CGIC (67% and 76%) and PGIC (64% and 63%). Deutetrabenazine was generally well tolerated in both groups. Conclusions: Deutetrabenazine treatment was associated with sustained improvements in total motor AIMS score, treatment success, and improved quality of life, and was well tolerated in younger and older adults with TD in this 3-year OLE study.

Untargeted Metabolomic Identification Of Diagnostic Biomarkers In Ectopic Pregnancy, Onur Turkoglu, Robert Quinn, Stewart F. Graham, Ray Bahado-Singh

Conference Presentation Abstracts

Introduction: Ectopic pregnancy (EP) is a potentially life-threatening condition and early diagnosis still remains a challenge, causing a delay in management leading to tubal rupture. Targeted metabolomics has been shown to identify novel biomarkers for the detection of ectopic pregnancy. Using untargeted metabolomics approach, we sought to identify putative plasma biomarkers for the detection of tubal EP compared to intrauterine pregnancies. Methods: This case-control study included prospective recruitment of 50 tubal EP cases and 50 early intrauterine pregnancy controls. Plasma samples were biochemically profiled using tandem liquid chromatographymass (MS/MS) spectrometry with untargeted metabolomics approach. To avoid over-fitting, datasets were randomly …

Anti-Glioblastoma Effects Of Phenolic Variants Of Benzoylphenoxyacetamide (Bpa) With High Potential For Blood Brain Barrier Penetration, Joanna Stalinska, Cecilia Vittori, Charles H. Ingraham Iv, Sean C. Carson, Karlie Plaisance-Bonstaff, Adam Lassak, Celeste Faia, Susan B. Colley, Francesca Peruzzi, Krzysztof Reiss, Branko S. Jursic

School of Medicine Faculty Publications

Glioblastomas are the most aggressive brain tumors for which therapeutic options are limited. Current therapies against glioblastoma include surgical resection, followed by radiotherapy plus concomitant treatment and maintenance with temozolomide (TMZ), however, these standard therapies are often ineffective, and average survival time for glioblastoma patients is between 12 and 18 months. We have previously reported a strong anti-glioblastoma activity of several metabolic compounds, which were synthetized based compounds, which were synthetized based on the chemical structure of a common lipid-lowering drug, fenofibrate, and share a general molecular skeleton of benzoylphenoxyacetamide (BPA). Extensive computational analyses of phenol and naphthol moieties added …

Perspective On Newborn Screening (Nbs): Evidence Sharing On Conditions To Be Included In Nbs In Pakistan, Hafsa Majid, Lena Jafri, Sibtain Ahmed, Khadija Humayun, Salman Kirmani, Natasha Bahadur Ali, Bushra Moiz, Aysha Habib, Bushra Afroze

Department of Pathology and Laboratory Medicine

Newborn screening aims at detecting treatable disorders early so that the treatment can be initiated to prevent mortality and morbidity. Such programmes are well established in most developed countries, and all newborns are screened for selected metabolic, endocrine and other disorders based on disease epidemiology, testing and treatment availability, efficiency and cost-effectiveness. Even in developing countries, such screening programmes are initiated using heel prick capillary blood collected on filter paper. The current narrative review was planned to provide a perspective with evidence in favour of starting newborn screening for different disorders. The programme project should be initiated nationwide, taking one …

Proteinuria In Thrombotic Microangiopathy (Tma) Can Be Associated With Adaptive Partial Podocytopathy With Focal Podocyte Hyperplasia, Megan Moore, Olabisi Afaolayan-Oloye, Wei Li, Hassan Kanaan, Ping Zhang

Conference Presentation Abstracts

Background: TMA associated renal failure is easy to understand, but it has been difficult to explain the significant proteinuria in some cases of TMA. We recently confirmed that 100% of hyperplastic podocytes in collapsing glomerulopathy stained positively for CD133 (a stem cell/progenitor marker) as previously reported. The goal of this study was to determine if there was significant fusion of foot processes (FFP) and CD133-positive hyperplastic podocytes in TMA to correlate with the proteinuria. Design: The study included 12 negative controls (renal parenchyma away from renal cell carcinoma) and 25 TMA cases, either induced by drugs or due to other …

A Soft Tissue Tumor With Eml4-Alk Fusion, Granular Cell Changes, Metastasis, And Response To Kinase Inhibitor Therapy In A Young Girl, Zhenhong Qu, Chris Hysell, Ping Zhang, Mark Micale

Conference Presentation Abstracts

Background: An increasing number of soft tissue neoplasms with fusion of well-defined driver genes are being discovered. We report such a case in a 3-year-old girl with a 2-year follow-up. Design: The patient first presented at age of 3.5 years with a painless right axillary/chest wall mass without constitutional symptoms. MRI demonstrated a 4.5 x 3.5 x 3.5 cm T2 hyper- and T1 hypointense mass. The mass was excised and showed a well-demarcated solid lesion with a homogeneous pale-white fleshy cut surface. No necrosis, myxoid or cystic change, hemorrhage, or calcification was noted. Microscopically, it was a variably hypercellular lesion …

A Soft Tissue Tumor With Eml4-Alk Fusion, Granular Cell Changes, Metastasis, And Response To Kinase Inhibitor Therapy In A Young Girl, Zhenhong Qu, Chris Hysell, Ping Zhang, Mark Micale

Conference Presentation Abstracts

Background: An increasing number of soft tissue neoplasms with fusion of well-defined driver genes are being discovered. We report such a case in a 3-year-old girl with a 2-year follow-up. Design: The patient first presented at age of 3.5 years with a painless right axillary/chest wall mass without constitutional symptoms. MRI demonstrated a 4.5 x 3.5 x 3.5 cm T2 hyper- and T1 hypointense mass. The mass was excised and showed a well-demarcated solid lesion with a homogeneous pale-white fleshy cut surface. No necrosis, myxoid or cystic change, hemorrhage, or calcification was noted. Microscopically, it was a variably hypercellular lesion …

Final Counts Of Monoclonal Gammopathy Of Renal Significance (Mgrs) After Bone Marrow Biopsies (Bmb) And Follow-Up, Brandon Metcalf, James Zhiyan Huang, Wei Li, Hassan Kanaan, Ping Zhang

Conference Presentation Abstracts

Background: MGRS is a relatively new concept for patients with renal paraprotein deposition (RPD) (except monoclonal cast nephropathy) with no bone marrow confirmed diagnosis of malignancy or premalignancy (< 10% monoclonal plasma cells). This concept has been used as a reason for a nephrology consult for a bone marrow biopsy (BMB), therefore it is important to evaluate the outcome of MGRS tentatively diagnosed via renal biopsy and confirmed by BMB. This study’s purpose was to identify what percentage of various subtypes of MGRS tentatively diagnosed via renal biopsy can be confirmed as MGRS by BMB and followup. Design: In total, 124 renal biopsies with variants of RPD were identified at our center out of 3811 renal biopsies (3.3% of overall cases) over past 10 years. Biopsy cases with known Myeloma, B Cell Lymphoma or Monoclonal Cast Nephropathy were separated as a heavy burden group. The remaining biopsies with RPD were considered as tentative MGRS diagnoses. Their BMB and clinical indices were followed up to determine the percent that resulted in a confirmed MGRS diagnosis. Results: Among the 124 renal paraprotein deposition cases, 43 cases (34.7%) were categorized to the heavy burden group (Figure). The remaining 81 cases with other variants of RPD were further divided into four categories based on the follow-up. Myeloma or Lymphoma were found in 34 cases (27.4%). Twelve outside consultation cases (10%) did not show follow-up biopsies as we were unable to obtain record access. BMB’s diagnosed as nonmalignant (6 cases, 4.8%) or premalignant (29 cases, 23.4%) were confirmed to be MGRS for a total of 35 cases (28.2%). Among the different categories of tentative MGRS, Monoclonal Light/Heavy Chain Deposition Diseases (L/HCDD) had the highest positivity rate for myeloma on the subsequent BMB. Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposition (PGNMID) had a high rate of nonmalignant or premalignant diagnosis by BMB. Monoclonal Amyloidosis had some nonmalignant and pre-malignant diagnoses after BMB although myeloma was associated with this renal entity. Conclusions: The data indicate that BMB is crucial for confirming a diagnosis of MGRS. The study also provides pathologists and clinicians with general expectations regarding the possible BMB outcome for the many variants of MGRS identified tentatively via renal biopsy.

Final Counts Of Monoclonal Gammopathy Of Renal Significance (Mgrs) After Bone Marrow Biopsies (Bmb) And Follow-Up, Brandon Metcalf, James Zhiyan Huang, Wei Li, Hassan Kanaan, Ping Zhang

Conference Presentation Abstracts

Background: MGRS is a relatively new concept for patients with renal paraprotein deposition (RPD) (except monoclonal cast nephropathy) with no bone marrow confirmed diagnosis of malignancy or premalignancy (< 10% monoclonal plasma cells). This concept has been used as a reason for a nephrology consult for a bone marrow biopsy (BMB), therefore it is important to evaluate the outcome of MGRS tentatively diagnosed via renal biopsy and confirmed by BMB. This study’s purpose was to identify what percentage of various subtypes of MGRS tentatively diagnosed via renal biopsy can be confirmed as MGRS by BMB and followup. Design: In total, 124 renal biopsies with variants of RPD were identified at our center out of 3811 renal biopsies (3.3% of overall cases) over past 10 years. Biopsy cases with known Myeloma, B Cell Lymphoma or Monoclonal Cast Nephropathy were separated as a heavy burden group. The remaining biopsies with RPD were considered as tentative MGRS diagnoses. Their BMB and clinical indices were followed up to determine the percent that resulted in a confirmed MGRS diagnosis. Results: Among the 124 renal paraprotein deposition cases, 43 cases (34.7%) were categorized to the heavy burden group (Figure). The remaining 81 cases with other variants of RPD were further divided into four categories based on the follow-up. Myeloma or Lymphoma were found in 34 cases (27.4%). Twelve outside consultation cases (10%) did not show follow-up biopsies as we were unable to obtain record access. BMB’s diagnosed as nonmalignant (6 cases, 4.8%) or premalignant (29 cases, 23.4%) were confirmed to be MGRS for a total of 35 cases (28.2%). Among the different categories of tentative MGRS, Monoclonal Light/Heavy Chain Deposition Diseases (L/HCDD) had the highest positivity rate for myeloma on the subsequent BMB. Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposition (PGNMID) had a high rate of nonmalignant or premalignant diagnosis by BMB. Monoclonal Amyloidosis had some nonmalignant and pre-malignant diagnoses after BMB although myeloma was associated with this renal entity. Conclusions: The data indicate that BMB is crucial for confirming a diagnosis of MGRS. The study also provides pathologists and clinicians with general expectations regarding the possible BMB outcome for the many variants of MGRS identified tentatively via renal biopsy.

Myeloperoxidase (Mpo) Immunostaining Can Identify Endothelial Injury Of Peritubular Capillaries And Glomeruli In Renal Antibody Mediated Rejection, Olabisi Afolayan-Oloye, Megan Moore, Wei Li, Hassan Kanaan, Ping Zhang

Conference Presentation Abstracts

Background: C4d positive staining in peritubular capillaries (PTC) of renal grafts has been used as a marker to support antibody mediated rejection (AMR), if there are morphologic changes of AMR and the renal recipient has positive donor specific antibody. But it is not clear if the C4d staining is related to any peritubular and glomerular injury during AMR. As injured endothelial cells can uptake the MPO into the endothelial cells, we used MPO immunostaining to highlight glomerular endothelial injury in crescentic glomerulonephritis previously. The goal of this study was to determine if there was an endothelial injury of PTC and …

Immortal Plain Gut Sutures: A Case Report, Hannah J. Anderson, Kathryn Lynn, Raziyeh Mahmoudzadeh, Tatyana Milman, Manish Jain, Sunir J Garg

Wills Eye Hospital Papers

Purpose: We report the case of a 79-year-old male who presented with irritation and foreign body sensation due to the subconjunctival plain gut sutures that did not dissolve three years after undergoing pars plana vitrectomy (PPV) for macular hole repair.

Observation: A 79-year-old male presented with foreign body sensation and irritation in his left eye. On slit lamp examination, the source of the foreign body sensation was two apparently intact plain gut sutures were visible under the conjunctiva, nasal and temporal to the cornea. These plain gut sutures were placed at the conclusion of PPV surgery three years prior to …

Clinical Validation Of A Multiplex Pcr-Based Detection Assay Using Saliva Or Nasopharyngeal Samples For Sars-Cov-2, Influenza A And B, Nikhil S. Sahajpal, Ashis K. Mondal, Sudha Ananth, Allan Njau, Kimya Jones, Pankaj Ahluwalia, Eesha Oza, Ted M. Ross, Vamsi Kota, Arvind Kothandaraman

Pathology, East Africa

The COVID-19 pandemic has resulted in significant diversion of human and material resources to COVID-19 diagnostics, to the extent that influenza viruses and co-infection in COVID-19 patients remains undocumented and pose serious public-health consequences. We optimized and validated a highly sensitive RT-PCR based multiplex-assay for the detection of SARS-CoV-2, influenza A and B viruses in a single-test. This study evaluated clinical specimens (n = 1411), 1019 saliva and 392 nasopharyngeal swab (NPS), tested using two-assays: FDA-EUA approved SARS-CoV-2 assay that targets N and ORF1ab gene, and the PKamp-RT-PCR based assay that targets SARS-CoV-2, influenza viruses A and B. Of the …

Radiation Doses In Patients Undergoing Computed Tomographic Coronary Artery Calcium Evaluation With A 64-Slice Scanner Versus A 256-Slice Scanner, Paul Madaj, Dong Li, Rine Nakanishi, Daniele Andreini, Gianluca Pontone, Edoardo Conte, Rachael O'Rourke, Christian Hamilton-Craig, Manojna Nimmagadda, Nicholas Kim, Badiha Fatima, Christopher Dailing, Kashif Shaikh, Chandana Shekar, Ju Hwan Lee, Matthew J Budoff

The Texas Heart Institute Journal

Computed tomographic coronary artery calcium scanning enables cardiovascular risk stratification; however, exposing patients to high radiation levels is an ongoing concern. New-generation computed tomographic systems use lower radiation doses than older systems do. To quantify comparative doses of radiation exposure, we prospectively acquired images from 220 patients with use of a 64-slice GE LightSpeed VCT scanner (control group, n=110) and a 256-slice GE Revolution scanner (study group, n=110). The groups were matched for age, sex, and body mass index; statistical analysis included t tests and linear regression.

The mean dose-length product was 21% lower in the study group than in …

The Status And Future Of Emergency Care In The Republic Of Kenya, J. Austin Lee, Grace Wanjiku, Naomi Nduku, Adam R. Aluisio, Ramu Kharel, John Tabu Simiyu, Benjamin Wachira

Emergency Medicine, East Africa

Kenya is a rapidly developing country with a growing economy and evolving health care system. In the decade since the last publication on the state of emergency care in Kenya, significant developments have occurred in the country's approach to emergency care. Importantly, the country decentralized most health care functions to county governments in 2013. Despite the triple burden of traumatic, communicable, and non-communicable diseases, the structure of the health care system in the Republic of Kenya is evolving to adapt to the important role for the care of emergent medical conditions. This report provides a ten-year interval update on the …

Prolonged Glycemic Adaptation Following Transition From A Low- To High-Carbohydrate Diet: A Randomized Controlled Feeding Trial, Lisa T Jansen, Nianlan Yang, Julia M W Wong, Tapan Mehta, David B Allison, David S Ludwig, Cara B Ebbeling

Children’s Nutrition Research Center Staff Publications

Objective: Consuming ≥150 g/day carbohydrate is recommended for 3 days before an oral glucose tolerance test (OGTT) for diabetes diagnosis. For evaluation of this recommendation, time courses of glycemic changes following transition from a very-low-carbohydrate (VLC) to high-carbohydrate diet were assessed with continuous glucose monitoring (CGM).

Research design and methods: After achieving a weight loss target of 15% (±3%) on the run-in VLC diet, participants (18-50 years old, BMI ≥27 kg/m2) were randomly assigned for 10 weeks to one of three isoenergetic diets: VLC (5% carbohydrate and 77% fat); high carbohydrate, high starch (HC-Starch) (57% carbohydrate and 25% fat, including …

Evaluation Of The Type I Error Rate When Using Parametric Bootstrap Analysis Of A Cluster Randomized Controlled Trial With Binary Outcomes And A Small Number Of Clusters, Lilian Golzarri-Arroyo, Stephanie L Dickinson, Yasaman Jamshidi-Naeini, Roger S Zoh, Andrew W Brown, Arthur H Owora, Peng Li, J Michael Oakes, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Cluster randomized controlled trials (cRCTs) are increasingly used but must be analyzed carefully. We conducted a simulation study to evaluate the validity of a parametric bootstrap (PB) approach with respect to the empirical type I error rate for a cRCT with binary outcomes and a small number of clusters.

Methods: We simulated a case study with a binary (0/1) outcome, four clusters, and 100 subjects per cluster. To compare the validity of the test with respect to error rate, we simulated the same experiment with K=10, 20, and 30 clusters, each with 2,000 simulated datasets. To test the null …

Teen Reactions To A Self-Representational Avatar: A Qualitative Exploration, Emily Baysden, Ninna Mendoza, Chishinga Callender, Zhigang Deng, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Purpose: This research presents findings from a qualitative exploration of the reactions of adolescents (12-14 years old) to navigating an exergame with an avatar created from multiple scans of the player (referred to as a self-representational avatar).

Methods: Post-gameplay interviews were conducted with adolescents following participation in a 20-min laboratory session (21.2 ± 0.8 min, mean ± SD) where the self-representational avatar was navigated through an exergame. Verbatim transcripts (n = 40) were coded and analyzed by 2 independent coders using hybrid thematic analysis for this secondary data analysis. Codes were reviewed to identify themes representing adolescents' reactions.

Results: Four …

Clonal Hematopoiesis Is Associated With Higher Risk Of Stroke, Romit Bhattacharya, Seyedeh M Zekavat, Jeffrey Haessler, Myriam Fornage, Laura Raffield, Md Mesbah Uddin, Alexander G Bick, Abhishek Niroula, Bing Yu, Christopher Gibson, Gabriel Griffin, Alanna C Morrison, Bruce M Psaty, William T Longstreth, Joshua C Bis, Stephen S Rich, Jerome I Rotter, Russell P Tracy, Adolfo Correa, Sudha Seshadri, Andrew Johnson, Jason M Collins, Kathleen M Hayden, Tracy E Madsen, Christie M Ballantyne, Siddhartha Jaiswal, Benjamin L Ebert, Charles Kooperberg, Joann E Manson, Eric A Whitsel, Nhlbi Trans-Omics For Precision Medicine Program, Pradeep Natarajan, Alexander P Reiner

Faculty, Staff and Student Publications

Background and purpose: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke.

Methods: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and …

Type 2 Diabetes Partitioned Polygenic Scores Associate With Disease Outcomes In 454,193 Individuals Across 13 Cohorts, Daniel Dicorpo, Jessica Leclair, Joanne B Cole, Chloé Sarnowski, Fariba Ahmadizar, Lawrence F Bielak, Anneke Blokstra, Erwin P Bottinger, Layal Chaker, Yii-Der I Chen, Ye Chen, Paul S De Vries, Tariq Faquih, Mohsen Ghanbari, Valborg Gudmundsdottir, Xiuqing Guo, Natalie R Hasbani, Dorina Ibi, M Arfan Ikram, Maryam Kavousi, Hampton L Leonard, Aaron Leong, Josep M Mercader, Alanna C Morrison, Girish N Nadkarni, Mike A Nalls, Raymond Noordam, Michael Preuss, Jennifer A Smith, Stella Trompet, Petra Vissink, Jie Yao, Wei Zhao, Eric Boerwinkle, Mark O Goodarzi, Vilmundur Gudnason, J Wouter Jukema, Sharon L R Kardia, Ruth J F Loos, Ching-Ti Liu, Alisa K Manning, Dennis Mook-Kanamori, James S Pankow, H Susan J Picavet, Naveed Sattar, Eleanor M Simonsick, W M Monique Verschuren, Ko Willems Van Dijk, Jose C Florez, Jerome I Rotter, James B Meigs, Josée Dupuis, Miriam S Udler

Faculty, Staff and Student Publications

OBJECTIVE: Type 2 diabetes (T2D) has heterogeneous patient clinical characteristics and outcomes. In previous work, we investigated the genetic basis of this heterogeneity by clustering 94 T2D genetic loci using their associations with 47 diabetes-related traits and identified five clusters, termed β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. The relationship between these clusters and individual-level metabolic disease outcomes has not been assessed.

RESEARCH DESIGN AND METHODS: Here we constructed individual-level partitioned polygenic scores (pPS) for these five clusters in 12 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (n = 454,193) …