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Glaucoma And Microglia-Induced Neuroinflammation, Makoto Ishikawa, Yukitoshi Izumi, Kota Sato, Taimu Sato, Charles F Zorumski, Hiroshi Kunikata, Toru Nakazawa

2020-Current year OA Pubs

Glaucoma is a multifactorial neurodegenerative disease characterized by a progressive optic neuropathy resulting in visual field defects. Elevated intraocular pressure (IOP) is the greatest risk factor for the development of glaucoma, and IOP reduction therapy is the only treatment currently available. However, there are many cases in which retinal degeneration progresses despite sufficient control of IOP. Therefore, it is important to elucidate the pathophysiology of glaucoma that is resistant to current IOP lowering therapies. Experiments using animal glaucoma models show the relationships between microglial neuroinflammatory responses and damage of retinal ganglion cells (RGCs). Inhibition of neuroinflammatory pathways associated with microglial …

Case Report: Peptide Receptor Radioligand Therapy In Metastatic Pediatric Neuroendocrine Tumors, Khanyisile Hlongwa, Olumayowa Kolade, Abdulilah Alnabulsi, Rachelle Steyn, Anita Brink, Vikas Prasad, Stuart More

2020-Current year OA Pubs

Neuroendocrine tumors (NETs) are not commonly diagnosed in children. Metastatic NETs tend to have poor outcomes, and this is seen in adult and pediatric populations. The role of somatostatin receptor imaging using [

Impact Of Multi-Source Data Augmentation On Performance Of Convolutional Neural Networks For Abnormality Classification In Mammography, Inchan Hwang, Hari Trivedi, Beatrice Brown-Mulry, Linglin Zhang, Vineela Nalla, Aimilia Gastounioti, Judy Gichoya, Laleh Seyyed-Kalantari, Imon Banerjee, Minjae Woo

2020-Current year OA Pubs

INTRODUCTION: To date, most mammography-related AI models have been trained using either film or digital mammogram datasets with little overlap. We investigated whether or not combining film and digital mammography during training will help or hinder modern models designed for use on digital mammograms.

METHODS: To this end, a total of six binary classifiers were trained for comparison. The first three classifiers were trained using images only from Emory Breast Imaging Dataset (EMBED) using ResNet50, ResNet101, and ResNet152 architectures. The next three classifiers were trained using images from EMBED, Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM), …

Inhibition Of Mirna Associated With A Disease-Specific Signature And Secreted Via Extracellular Vesicles Of Systemic Lupus Erythematosus Patients Suppresses Target Organ Inflammation In A Humanized Mouse Model, Nicholas A Young, Emily Schwarz, Braden M Zeno, Shane Bruckner, Rosana A Mesa, Kyle Jablonski, Lai-Chu Wu, Elisha D O Roberson, Wael N Jarjour

2020-Current year OA Pubs

INTRODUCTION: Distinct, disease-associated intracellular miRNA (miR) expression profiles have been observed in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients. Additionally, we have identified novel estrogenic responses in PBMCs from SLE patients and demonstrated that estrogen upregulates toll-like receptor (TLR)7 and TLR8 expression. TLR7 and TLR8 bind viral-derived single-stranded RNA to stimulate innate inflammatory responses, but recent studies have shown that miR-21, mir-29a, and miR-29b can also bind and activate these receptors when packaged and secreted in extracellular vesicles (EVs). The objective of this study was to evaluate the association of EV-encapsulated small RNA species in SLE …

Lymphatic Contractile Dysfunction In Mouse Models Of Cantú Syndrome With Katp Channel Gain-Of-Function, Michael J Davis, Jorge A Castorena-Gonzalez, Hae Jin Kim, Min Li, Maria Remedi, Colin G Nichols

2020-Current year OA Pubs

Cantú Syndrome (CS) is an autosomal dominant disorder caused by gain-of-function (GoF) mutations in the Kir6.1 and SUR2 subunits of K

Plasma And Cerebrospinal Fluid Proteomic Signatures Of Acutely Sleep-Deprived Humans: An Exploratory Study, Ana Vaquer-Alicea, Jinsheng Yu, Haiyan Liu, Brendan P Lucey

2020-Current year OA Pubs

STUDY OBJECTIVES: Acute sleep deprivation affects both central and peripheral biological processes. Prior research has mainly focused on specific proteins or biological pathways that are dysregulated in the setting of sustained wakefulness. This exploratory study aimed to provide a comprehensive view of the biological processes and proteins impacted by acute sleep deprivation in both plasma and cerebrospinal fluid (CSF).

METHODS: We collected plasma and CSF from human participants during one night of sleep deprivation and controlled normal sleep conditions. One thousand and three hundred proteins were measured at hour 0 and hour 24 using a high-scale aptamer-based proteomics platform (SOMAscan) …

Development Of An In-Vitro High-Throughput Screening System To Identify Modulators Of Genitalia Development, Yan Yin, Meade Haller, Tian Li, Liang Ma

2020-Current year OA Pubs

Sexually dimorphic outgrowth and differentiation of the embryonic genital tubercles (GTs) give rise to the penis in males and the clitoris in females. Defects in androgen production or in response to androgen signaling can lead to various congenital penile anomalies in both mice and humans. Due to lack of a high-throughput screening system, identification of crucial regulators of GT sexual differentiation has been slow. To overcome this research barrier, we isolated embryonic GT mesenchymal (GTme) cells to model genitalia growth and differentiation in vitro. Using either a mechanical or fluorescence-activated cell sorting-assisted purification method, GTme cells were isolated and assayed …

Editorial, Faizan Ali

Journal of Global Hospitality and Tourism

I am pleased to present the third issue of Journal of Global Hospitality and Tourism (JGHT), Volume 2, Issue 1. This issue focuses on ensuring the journal’s scope and strengthening its position in both conceptual developments and practical applications in global hospitality and tourism through publication of five quality manuscripts and 2 academic viewpoints: five full papers that underwent rigorous double-blind reviewing, an academic viewpoint, and an industry viewpoint. The present issue of JGHT contains five full papers, written by fourteen authors located in four different countries and affiliated with eight different universities.

Patient Experiences With Thyroid Nodules: A Qualitative Interview Survey, Matthew R Naunheim, Manuela Von Sneidern, Molly N Huston, Okenwa C Okose, Amr H Abdelhamid Ahmed, Gregory W Randolph, Mark G Shrime

2020-Current year OA Pubs

OBJECTIVE: To qualitatively explore the broad set of preferences and attitudes patients have about thyroid nodules, which influence the decision-making process.

STUDY DESIGN: A descriptive survey design was administered as interviews.

SETTING: Outpatient thyroid surgery clinic.

METHODS: Semistructured interviews were conducted with 20 patients presenting for initial evaluation of thyroid nodules at a surgeon's office. Probative, open-ended questions were posed regarding diagnosis, treatment, risk attitudes, and the decision-making process. Thematic analysis was used to develop code-transcribed interviews, and an iterative refinement resulted in underlying themes.

RESULTS: During the diagnostic process, patients integrated emotional responses (fear, anxiety, and shock) with rationale …

Intra-Articular Aav9 Α-L-Iduronidase Gene Replacement In The Canine Model Of Mucopolysaccharidosis Type I, Raymond Yu-Jeang Wang, Shih-Hsin Kan, Haoyue Zhang, Jodi D Smith, Afshin Aminian, Elizabeth Snella, Jackie K Jens, Sarah P Young, Patricia I Dickson, N Matthew Ellinwood

2020-Current year OA Pubs

Mucopolysaccharidosis type I (MPS I), an inherited lysosomal storage disorder characterized by deficiency of

Chronic Gcpii (Glutamate-Carboxypeptidase-Ii) Inhibition Reduces Pt217tau Levels In The Entorhinal And Dorsolateral Prefrontal Cortices Of Aged Macaques, Shveta Bathla, Nicolas Barthelemy, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Current approaches for treating sporadic Alzheimer's disease (sAD) focus on removal of amyloid beta 1-42 (Aβ

METHODS: Aged rhesus macaques were treated daily with the GCPII inhibitor, 2-MPPA (2-3-mercaptopropyl-penanedioic acid (2-MPPA)),Aged rhesus macaques were treated daily with the GCPII inhibitor, 2-MPPA (2-3-mercaptopropyl-penanedioic acid (2-MPPA)).

RESULTS: Aged macaques that received 2-MPPA had significantly lower pT217Tau levels in dlPFC and ERC, and had lowered plasma pT217Tau levels from baseline. pT217Tau levels correlated significantly with GCPII activity in dlPFC. Both 2-MPPA- and vehicle-treated monkeys showed cognitive improvement; 2-MPPA had no apparent side effects. Exploratory CSF analyses indicated reduced pS202Tau with 2-MPPA administration, …

Case Report: Insulin Hypersensitivity In Youth With Type 1 Diabetes, Einas H Alkhatib, Jody B Grundman, Anna M Adamusiak, Melena D Bellin, Joel P Brooks, Kevin S Buckley, Erin M Janssen, Maleewan Kitcharoensakkul, Kyle P Mcnerney, Thea L Pfeifer, Brooke I Polk, Brynn E Marks

2020-Current year OA Pubs

OBJECTIVE: Immediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration required for the treatment of type 1 diabetes (T1D).

METHODS: We present four cases of insulin hypersensitivity reactions occurring in youth with T1D and a literature review of this topic.

RESULTS: Insulin hypersensitivity reactions included types I, III, and IV with presentations ranging from localized urticaria, erythematous nodules, and eczematous plaques to anaphylaxis with respiratory distress. Reactions occurred in youth with newly diagnosed T1D and in those with long-standing T1D who were using both injection and …

Factors Influencing Delayed Clearance Of High Dose Methotrexate (Hdmtx) In Pediatric, Adolescent, And Young Adult Oncology Patients, Ema Mosleh, Stacy Snyder, Ningying Wu, Daniel N Willis, Rema Malone, Robert J Hayashi

2020-Current year OA Pubs

PURPOSE: To identify modifiable risk factors associated with prolonged clearance of methotrexate in pediatric, adolescent, and young adult (AYA) oncology patients receiving high dose methotrexate (HDMTX).

DESIGN/METHOD: A single institution, retrospective chart review of patients receiving HDMTX between 2010-2017. Patients had a diagnosis of either leukemia or osteosarcoma. Data included demographics, concurrent intravenous (IV) medications, IV fluids (IVF) administered, urine output (UO), and rises in serum creatinine (RSC) reflective of renal toxicity (RT). Outcome measures included 1) delayed targeted MTX clearance (DC), 2) actual time to clearance (TTC) and 3) length of stay (LOS).

RESULTS: Data from 447 HDMTX administrations …

Gene-Educational Attainment Interactions In A Multi-Population Genome-Wide Meta-Analysis Identify Novel Lipid Loci, Lisa De Las Fuentes, Karen L. Schwander, Yun Ju Sung, Mary F. Feitosa, Ahn Do, C. Charles Gu, Treva K. Rice, Mary K. Wojczynski, Michael M. Province, Dabeeru C. Rao, Et Al.

2020-Current year OA Pubs

No abstract provided.

What Can State Medical Boards Do To Effectively Address Serious Ethical Violations?, Tristan Mcintosh, Elizabeth Pendo, Heidi A Walsh, Kari A Baldwin, Patricia King, Emily E Anderson, Catherine V Caldicott, Jeffrey D Carter, Sandra H Johnson, Katherine Mathews, William A Norcross, Dana C Shaffer, James M Dubois

2020-Current year OA Pubs

State Medical Boards (SMBs) can take severe disciplinary actions (e.g., license revocation or suspension) against physicians who commit egregious wrongdoing in order to protect the public. However, there is noteworthy variability in the extent to which SMBs impose severe disciplinary action. In this manuscript, we present and synthesize a subset of 11 recommendations based on findings from our team's larger consensus-building project that identified a list of 56 policies and legal provisions SMBs can use to better protect patients from egregious wrongdoing by physicians.

Approach To Vaccinating The Pediatric Solid Organ Transplant Candidate And Recipient, Carol M Kao, Marian G Michaels

2020-Current year OA Pubs

Solid organ transplantation (SOT) candidates and recipients are at increased risk for morbidity and mortality from vaccine-preventable infections. Children are at particular risk given that they may not have completed their primary immunization series at time of transplant or have acquired natural immunity to pathogens from community exposures. Multiple society guidelines exist for vaccination of SOT candidate and recipients, although challenges remain given limited safety and efficacy data available for pediatric SOT recipients, particularly for live-vaccines. After transplant, individual patient nuances regarding exposure risks and net state of immunosuppression will impact timing of immunizations. The purpose of this review is …

Rare Predicted Loss-Of-Function Variants Of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19, Daniela Matuozzo, Megan A. Cooper, Et Al.

2020-Current year OA Pubs

No abstract provided.

Healthcare-Associated Infections (Hais) During The Coronavirus Disease 2019 (Covid-19) Pandemic: A Time-Series Analysis, John M Sahrmann, Katelin B Nickel, Dustin Stwalley, Erik R Dubberke, Patrick G Lyons, Andrew P Michelson, Kathleen M Mcmullen, Sumanth Gandra, Margaret A Olsen, Jennie H Kwon, Jason P Burnham

2020-Current year OA Pubs

OBJECTIVE: To use interrupted time-series analyses to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infections (HAIs). We hypothesized that the pandemic would be associated with higher rates of HAIs after adjustment for confounders.

DESIGN: We conducted a cross-sectional study of HAIs in 3 hospitals in Missouri from January 1, 2017, through August 31, 2020, using interrupted time-series analysis with 2 counterfactual scenarios.

SETTING: The study was conducted at 1 large quaternary-care referral hospital and 2 community hospitals.

PARTICIPANTS: All adults ≥18 years of age hospitalized at a study hospital for ≥48 hours were included in …

A Single-Molecule Method For Measuring Fluorophore Labeling Yields For The Study Of Membrane Protein Oligomerization In Membranes, Melanie Ernst, Tugba N. Ozturk, Janice L. Robertson

2020-Current year OA Pubs

Membrane proteins are often observed as higher-order oligomers, and in some cases in multiple stoichiometric forms, raising the question of whether dynamic oligomerization can be linked to modulation of function. To better understand this potential regulatory mechanism, there is an ongoing effort to quantify equilibrium reactions of membrane protein oligomerization directly in membranes. Single-molecule photobleaching analysis is particularly useful for this as it provides a binary readout of fluorophores attached to protein subunits at dilute conditions. However, any quantification of stoichiometry also critically requires knowing the probability that a subunit is fluorescently labeled. Since labeling uncertainty is often unavoidable, we …

Sik3 And Wnk Converge On Fray To Regulate Glial K+ Buffering And Seizure Susceptibility, Lorenzo Lones, Aaron Diantonio

2020-Current year OA Pubs

Glial cells play a critical role in maintaining homeostatic ion concentration gradients. Salt-inducible kinase 3 (SIK3) regulates a gene expression program that controls K+ buffering in glia, and upregulation of this pathway suppresses seizure behavior in the eag, Shaker hyperexcitability mutant. Here we show that boosting the glial SIK3 K+ buffering pathway suppresses seizures in three additional molecularly diverse hyperexcitable mutants, highlighting the therapeutic potential of upregulating glial K+ buffering. We then explore additional mechanisms regulating glial K+ buffering. Fray, a transcriptional target of the SIK3 K+ buffering program, is a kinase that promotes K+ uptake by activating the Na+/K+/Cl- …

Multi-Omic Association Study Identifies Dna Methylation-Mediated Genotype And Smoking Exposure Effects On Lung Function In Children Living In Urban Settings, Matthew Dapas, Michelle A. Gill, Et Al

2020-Current year OA Pubs

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; βz = -0.31, …

A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer

2020-Current year OA Pubs

PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were …

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al.

2020-Current year OA Pubs

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …

Factors Associated With Persistent Postsurgical Pain After Total Knee Or Hip Joint Replacement: A Systematic Review And Meta-Analysis, Arunangshu Ghoshal, Shivam Bhanvadia, Som Singh, Lauren Yaeger, Simon Haroutounian

2020-Current year OA Pubs

Studies have identified demographic, clinical, psychosocial, and perioperative variables associated with persistent pain after a variety of surgeries. This study aimed to perform a systematic review and meta-analysis of factors associated with persistent pain after total knee replacement (TKR) and total hip replacement (THR) surgeries. To meet the inclusion criteria, studies were required to assess variables before or at the time of surgery, include a persistent postsurgical pain (PPSP) outcome measure at least 2 months after a TKR or THR surgery, and include a statistical analysis of the effect of the risk factor(s) on the outcome measure. Outcomes from studies …

Pregnancy-Induced Differential Expression Of Sars-Cov-2 And Influenza A Viral Entry Factors In The Lower Respiratory Tract, Tusar Giri, Santosh Panda, Arvind Palanisamy

2020-Current year OA Pubs

Despite differences in the clinical presentation of coronavirus disease-19 and pandemic influenza in pregnancy, fundamental mechanistic insights are currently lacking because of the difficulty in recruiting critically ill pregnant subjects for research studies. Therefore, to better understand host-pathogen interaction during pregnancy, we performed a series of foundational experiments in pregnant rats at term gestation to assess the expression of host entry factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) and genes associated with innate immune response in the lower respiratory tract. We report that pregnancy is characterized by a decrease in host factors mediating …

Adherence To And Experiences Of K-12 Students In Modified And Standard Home Quarantine During The Sars-Cov-2 Pandemic In Missouri, Mary Claire Worrell, Sara Malone, Patrick Dawson, Stephanie A. Fritz, Ebony Thomas, Bre Peeler, Catherine Rains, Sarah C. Tinker, John C. Neatherlin, Lisa Barrios, Jon Mooney, Katie Towns, Jason Newland, Johanna S. Salzer

2020-Current year OA Pubs

BACKGROUND: In November 2020, during the SARS-CoV-2 pandemic, Missouri allowed local public health jurisdictions the option to implement a modified quarantine policy allowing kindergarten through 12 (K-12) students with low-risk exposures to continue in-person learning. We assessed adherence to quarantine among participants in modified quarantine and standard home quarantine and the psychosocial impacts of quarantine on students and families.

METHODS: In January-March 2021, as part of an investigation of in-school transmission of SARS-CoV-2, parents of 586 participating K-12 students identified as a close contact with a person with SARS-CoV-2 were sent a survey to assess their activities and psychosocial impacts …

X-Ray And Mr Contrast Bearing Nanoparticles Enhance The Therapeutic Response Of Image-Guided Radiation Therapy For Oral Cancer, Gayatri Sharma, Mir Hadi Razeghi Kondelaji, Guru P. Sharma, Christopher Hansen, Abdul K. Parchur, Shayan Shafiee, Jaidip M. Jagtap, Brian Fish, Carmen Bergom, Eric Paulson, William A. Hall, Heather A. Himburg, Amit Joshi

2020-Current year OA Pubs

INTRODUCTION: Radiation therapy for head and neck squamous cell carcinoma is constrained by radiotoxicity to normal tissue. We demonstrate 100 nm theranostic nanoparticles for image-guided radiation therapy planning and enhancement in rat head and neck squamous cell carcinoma models.

METHODS: PEG conjugated theranostic nanoparticles comprising of Au nanorods coated with Gadolinium oxide layers were tested for radiation therapy enhancement in 2D cultures of OSC-19-GFP-luc cells, and orthotopic tongue xenografts in male immunocompromised Salt sensitive or SS rats via both intratumoral and intravenous delivery. The radiation therapy enhancement mechanism was investigated.

RESULTS: Theranostic nanoparticles demonstrated both X-ray/magnetic resonance contrast in a …

Small Molecule Inhibiting Microglial Nitric Oxide Release Could Become A Potential Treatment For Neuroinflammation, Philipp Jordan, Amanda Costa, Et Al.

2020-Current year OA Pubs

Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or …

Imputation Of Missing Values For Cochlear Implant Candidate Audiometric Data And Potential Applications, Cole Pavelchek, Andrew P. Michelson, Amit Walia, Amanda Ortmann, Jacques Herzog, Craig A. Buchman, Matthew A. Shew

2020-Current year OA Pubs

OBJECTIVE: Assess the real-world performance of popular imputation algorithms on cochlear implant (CI) candidate audiometric data.

METHODS: 7,451 audiograms from patients undergoing CI candidacy evaluation were pooled from 32 institutions with complete case analysis yielding 1,304 audiograms. Imputation model performance was assessed with nested cross-validation on randomly generated sparse datasets with various amounts of missing data, distributions of sparsity, and dataset sizes. A threshold for safe imputation was defined as root mean square error (RMSE) <10dB. Models included univariate imputation, interpolation, multiple imputation by chained equations (MICE), k-nearest neighbors, gradient boosted trees, and neural networks.

RESULTS: Greater quantities of missing data were associated with worse performance. Sparsity in audiometric data is not uniformly distributed, as inter-octave frequencies are less commonly …

Higher Dose Oral Fluconazole For The Treatment Of Aids-Related Cryptococcal Meningitis (Hiflac)--Report Of A5225, A Multicentre, Phase I/Ii, Two-Stage, Dose-Finding, Safety, Tolerability And Efficacy Randomised, Amphotericin B-Controlled Trial Of The Aids Clinical Trials Group, Umesh G. Lalloo, David B. Clifford, Et Al.

2020-Current year OA Pubs

BACKGROUND: The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken.

METHODS: In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio. A particular dose was not tested in Stage 2 if there were significant …