Research Spotlight

Posted June 24th 2020

Are cost advantages from a modern Indian hospital transferable to the United States?

Michael J. Mack M.D.

Michael J. Mack M.D.

Erhun, F., R. S. Kaplan, V. G. Narayanan, K. Brayton, M. Kalani, M. C. Mazza, C. Nguyen, T. Platchek, B. Mistry, R. Mann, D. Kazi, C. Pinnock, K. A. Schulman, J. Xue, D. Ballard, M. Mack, B. James, G. Poulsen, J. Punnen, D. Shetty and A. Milstein (2020). “Are cost advantages from a modern Indian hospital transferable to the United States?” Am Heart J 224: 148-155.

Full text of this article.

BACKGROUND: Multiple modern Indian hospitals operate at very low cost while meeting US-equivalent quality accreditation standards. Though US hospitals face intensifying pressure to lower their cost, including proposals to extend Medicare payment rates to all admissions, the transferability of Indian hospitals’ cost advantages to US peers remains unclear. METHODS: Using time-driven activity-based costing methods, we estimate the average cost of personnel and space for an elective coronary artery bypass graft (CABG) surgery at two American hospitals and one Indian hospital (NH). All three hospitals are Joint Commission accredited and have reputations for use of modern performance management methods. Our case study applies several analytic steps to distinguish transferable from non-transferable sources of NH’s cost savings. RESULTS: After removing non-transferable sources of efficiency, NH’s residual cost advantage primarily rests on shifting tasks to less-credentialed and/or less-experienced personnel who are supervised by highly-skilled personnel when perceived risk of complications is low. NH’s high annual CABG volume facilitates such supervised work “downshifting.” The study is subject to limitations inherent in case studies, does not account for the younger age of NH’s patients, or capture savings attributable to NH’s negligible frequency of re-admission or post-acute care facility placement. CONCLUSIONS: Most transferable bases for a modern Indian hospital’s cost advantage would require more flexible American states’ hospital and health professional licensing regulations, greater family participation in inpatient care, and stronger support by hospital executives and clinicians for substantially lowering the cost of care via regionalization of complex surgeries and weekend use of costly operating rooms.


Posted June 24th 2020

Propagation of Pathological α-Synuclein from the Urogenital Tract to the Brain Initiates MSA-like Syndrome.

Erxi Wu, Ph.D.

Erxi Wu, Ph.D.

Ding, X., L. Zhou, X. Jiang, H. Liu, J. Yao, R. Zhang, D. Liang, F. Wang, M. Ma, B. Tang, E. Wu, J. Teng and X. Wang (2020). “Propagation of Pathological α-Synuclein from the Urogenital Tract to the Brain Initiates MSA-like Syndrome.” iScience May 15;23(6):101166. [Epub ahead of print].

Full text of this article.

The neuropathological feature of multiple system atrophy (MSA), a fatal adult-onset disorder without effective therapy, is the accumulation of pathological α-synuclein (α-Syn) in the central nervous system (CNS). Here we show that pathological α-Syn exists in nerve terminals in detrusor and external urethral sphincter (EUS) of patients with MSA. Furthermore, α-Syn-preformed fibrils (PFFs) injected in the EUS or detrusor in TgM83(+/-) mice initiated the transmission of pathological α-Syn from the urogenital tract to brain via micturition reflex pathways, and these mice developed widespread phosphorylated α-Syn inclusion pathology together with phenotypes. In addition, urinary dysfunction and denervation-reinnervation of external anal sphincter were detected earlier in the mouse models with α-Syn PFFs inoculation before the behavioral manifestations. These results suggest that pathological α-Syn spreading through the micturition reflex pathways retrogradely from the urogenital tract to CNS may lead to urinary dysfunction in patients with MSA, which is different from the etiology of idiopathic Parkinson disease.


Posted June 24th 2020

CFTR variant testing: a technical standard of the American College of Medical Genetics and Genomics (ACMG).

Anthony R. Gregg, M.D.

Anthony R. Gregg, M.D.

Deignan, J. L., C. Astbury, G. R. Cutting, D. Del Gaudio, A. R. Gregg, W. W. Grody, K. G. Monaghan and S. Richards (2020). “CFTR variant testing: a technical standard of the American College of Medical Genetics and Genomics (ACMG).” Genet Med May 14. [Epub ahead of print].

Full text of this article.

Pathogenic variants in the CFTR gene are causative of classic cystic fibrosis (CF) as well as some nonclassic CF phenotypes. In 2001, CF became the first target of pan-ethnic universal carrier screening by molecular methods. The American College of Medical Genetics and Genomics (ACMG) recommended a core panel of 23 disease-causing variants as the minimal set to be included in pan-ethnic carrier screening of individuals with no family history of the disease, and these variants were usually assessed using targeted methods. The original recommendation also left open the option for laboratories to offer expanded CFTR variant panels; however, at the time, expanded CFTR variant panels were met with some controversy on the basis of the available technologies and the limited phenotypic knowledge of rare variants. Both of those aspects have now evolved, prompting this update of the ACMG technical standards for CFTR variant testing.


Posted June 24th 2020

A Human Lung Challenge Model to Evaluate the Safety and Immunogenicity of PPD and Live Bacillus Calmette-Guérin.

Shashikant Srivastava M.D.

Shashikant Srivastava M.D.

Davids, M., A. Pooran, C. Hermann, L. Mottay, F. Thompson, J. Cardenas, J. Gu, T. Koeuth, R. Meldau, J. Limberis, P. Gina, S. Srivastava, B. Calder, A. Esmail, M. Tomasicchio, J. Blackburn, T. Gumbo and K. Dheda (2020). “A Human Lung Challenge Model to Evaluate the Safety and Immunogenicity of PPD and Live Bacillus Calmette-Guérin.” Am J Respir Crit Care Med 201(10): 1277-1291.

Full text of this article.

Rationale: A human model to better understand tuberculosis immunopathogenesis and facilitate vaccine development is urgently needed.Objectives: We evaluated the feasibility, safety, and immunogenicity of live bacillus Calmette-Guérin (BCG) in a lung-oriented controlled human infection model.Methods: We recruited 106 healthy South African participants with varying degrees of tuberculosis susceptibility. Live BCG, sterile PPD, and saline were bronchoscopically instilled into separate lung segments (n = 65). A control group (n = 34) underwent a single bronchoscopy without challenge. The primary outcome was safety. Cellular and antibody immune signatures were identified in BAL before and 3 days after challenge using flow cytometry, ELISA, RNA sequencing, and mass spectrometry.Measurements and Main Results: The frequency of adverse events was low (9.4%; n = 10), similar in the challenge versus control groups (P = 0.8), and all adverse events were mild and managed conservatively in an outpatient setting. The optimal PPD and BCG dose was 0.5 TU and 10(4) cfu, respectively, based on changes in BAL cellular profiles (P = 0.02) and antibody responses (P = 0.01) at incremental doses before versus after challenge. At 10(4) versus 10(3) cfu BCG, there was a significant increase in number of differentially expressed genes (367 vs. 3; P < 0.001) and dysregulated proteins (64 vs. 0; P < 0.001). Immune responses were highly setting specific (in vitro vs. in vivo) and compartment specific (BAL vs. blood) and localized to the challenged lung segments.Conclusions: A lung-oriented mycobacterial controlled human infection model using live BCG and PPD is feasible and safe. These data inform the study of tuberculosis immunopathogenesis and strategies for evaluation and development of tuberculosis vaccine candidates.


Posted June 24th 2020

Sugammadex Administration to Facilitate Timely Neurologic Examination in the Traumatic Brain Injury Patient.

Jonathan M. Curley, M.D.

Jonathan M. Curley, M.D.

Curley, J. M., D. P. Ciceri and W. C. Culp, Jr. (2020). “Sugammadex Administration to Facilitate Timely Neurologic Examination in the Traumatic Brain Injury Patient.” Neurocrit Care 32(3): 880-882.

Full text of this article.

Neuromuscular blocking agents are frequently administered to traumatic brain injury patients during initial airway management; however, paralytics can delay diagnosis and treatment by impeding the neurologic examination. Sugammadex is a relatively new medication approved for reversal of amino-steroid paralytic agents such as rocuronium or vecuronium. We describe the use of sugammadex to reverse prolonged rocuronium-induced paralysis in a dialysis-dependent patient who suffered a traumatic brain injury. This reversal allowed for immediate evaluation by a neurosurgeon, neurosurgical intervention, and subsequent detection of patient neurologic deterioration by examination which otherwise may have been mistaken for prolonged paralysis. To the authors’ knowledge, the use of sugammadex for this purpose has not previously been reported. [No abstract; excerpt from article].