Publications by authors named "James Williams"

630 Publications

Transition of Care from Pediatric to Adult Care in Eosinophilic Esophagitis: Insights from a Patient Perspective Survey.

J Pediatr Gastroenterol Nutr 2021 Sep 17. Epub 2021 Sep 17.

Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics, University of Colorado School of Medicine, Digestive Health Institute, Children's Hospital of Colorado Aurora, CO Trinity Partners, LLC, Waltham, MA Shire Human Genetic Therapies, Inc., a Takeda company, Cambridge, MA Takeda Pharmaceuticals USA, Inc., Lexington, MA The Department of Internal Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.

Abstract: Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease. Patients with a childhood diagnosis require ongoing disease management in adulthood. However, knowledge of the patient experience during pediatric to adult healthcare transition is lacking. Here, an online survey captured patient perceptions of the challenges faced by patients with EoE in the USA during transition to adult healthcare, and which resources, if implemented, could better support transition. Of 67 respondents, 91% (n = 61) were under adult care at the time of survey completion. Aspects that respondents struggled with most included meal planning, food shopping, cooking/finding foods that did not exacerbate their condition, and knowledge of insurance coverage. Although most respondents reported confidence in having the knowledge to manage their EoE, almost half of the respondents worried about managing their condition in the future. Resources detailing diet, medication and insurance management strategies could support the transition to adult healthcare for patients with EoE.
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http://dx.doi.org/10.1097/MPG.0000000000003303DOI Listing
September 2021

Improved Potency And Safety Of DNA-encoded Antibody Therapeutics Through Plasmid Backbone And Expression Cassette Engineering.

Hum Gene Ther 2021 Sep 4. Epub 2021 Sep 4.

University of Leuven, Herestraat 49, LEUVEN, Belgium, 3000;

DNA-encoded delivery of antibodies presents a labor- and cost-effective alternative to conventional antibody therapeutics. This study aims to improve potency and safety of this approach by evaluating various plasmid backbones and expression cassettes. In vitro, antibody levels consistently improved with decreasing sizes of backbone, ranging from conventional to minimal. In vivo, following intramuscular electrotransfer in mice, the correlation was less consistent. While the largest conventional plasmid (10.2 kb) gave the lowest mAb levels, a regular conventional plasmid (8.6 kb) demonstrated similar levels as a minimal Nanoplasmid (6.8 kb). A reduction in size beyond a standard conventional backbone thus did not improve mAb levels in vivo. Cassette modifications, such as swapping antibody chain order or use of two versus a single encoding plasmid, significantly increased antibody expression in vitro, but failed to translate in vivo. Conversely, a significant improvement in vivo but not in vitro was found with a set of muscle-specific promoters, of which a newly engineered variant gave roughly 1.5- to 2-fold higher plasma antibody concentrations than the ubiquitous CAG promoter. In conclusion, despite the limited translation between in vitro and in vivo, we identified various clinically relevant improvements to our DNA-based antibody platform, both in potency and biosafety.
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http://dx.doi.org/10.1089/hum.2021.105DOI Listing
September 2021

An evaluation of strategies for restoring a degraded New Zealand scallop fishery using stochastic dynamic simulation modelling.

J Environ Manage 2021 Sep 2;299:113547. Epub 2021 Sep 2.

National Institute of Water and Atmospheric Research Ltd (NIWA), 10 Kyle Street, Riccarton, Christchurch, 8011, New Zealand.

A decision-theoretical approach was used to evaluate strategies to rebuild a severely depleted scallop (Pecten novaezelandiae) populations in the Tasman Bay and Golden Bay of New Zealand. These strategies were: no intervention, cessation of seabed bottom contact fishing, and reduction of sediment and nutrient runoff from surrounding land through on-farm practices. Our approach combined outputs of estimated effects of on-farm practices on erosion and nutrient reduction with a stochastic dynamic model of the scallop populations. The most effective individual intervention is eliminating bottom contact fishing through dredging and trawling which increased scallop biomass on average by 73% compared to the no intervention scenario. Although on-farm practices have reduced sedimentation and nutrient runoff significantly (28-36% and 2%, respectively), they have no effect on scallop biomass if implemented individually and led to only marginal improvements in scallop biomass if implemented alongside cessation of bottom contact fishing (2-4%). Although our results showed, on average, substantial recovery in the scallop population when reducing seabed bottom contact and water pollution, the large uncertainty boundaries makes it unclear whether these improvements would be realized. The long-term success of such strategies will depend on the available habitat being able to sustain high densities of healthy scallop adults and recruits, a situation that has been posited in our analysis. Where scallop juvenile survival is compromised by sedimentation, nutrient pollution, or other exogenous influences, proposed interventions may be insufficient to aid recovery.
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http://dx.doi.org/10.1016/j.jenvman.2021.113547DOI Listing
September 2021

B-Doped δ-Layers and Nanowires from Area-Selective Deposition of BCl on Si(100).

ACS Appl Mater Interfaces 2021 Sep 18;13(34):41275-41286. Epub 2021 Aug 18.

Laboratory for Physical Sciences, 8050 Greenmead Drive, College Park, Maryland 20740, United States.

Atomically precise, δ-doped structures forming electronic devices in Si have been routinely fabricated in recent years by using depassivation lithography in a scanning tunneling microscope (STM). While H-based precursor/monatomic resist chemistries for incorporation of donor atoms have dominated these efforts, the use of halogen-based chemistries offers a promising path toward atomic-scale manufacturing of acceptor-based devices. Here, B-doped δ-layers were fabricated in Si(100) by using BCl as an acceptor dopant precursor in ultrahigh vacuum. Additionally, we demonstrate compatibility of BCl with both H and Cl monatomic resists to achieve area-selective deposition on Si. In comparison to bare Si, BCl adsorption selectivity ratios for H- and Cl-passivated Si were determined by secondary ion mass spectrometry depth profiling (SIMS) to be 310(10):1 and 1529(5):1, respectively. STM imaging revealed that BCl adsorbed readily on bare Si at room temperature, with SIMS measurements indicating a peak B concentration greater than 1.2(1) × 10 cm with a total areal dose of 1.85(1) × 10 cm resulting from a 30 langmuir BCl dose at 150 °C. In addition, SIMS showed a δ-layer thickness of ∼0.5 nm. Hall bar measurements of a similar sample were performed at 3.0 K, revealing a sheet resistance of ρ = 1.9099(4) kΩ □, a hole carrier concentration of = 1.90(2) × 10 cm, and a hole mobility of μ = 38.0(4) cm V s without performing an incorporation anneal. Finally, 15 nm wide B δ-doped nanowires were fabricated from BCl and were found to exhibit ohmic conduction. This validates the use of BCl as a dopant precursor for atomic-precision fabrication of acceptor-doped devices in Si and enables development of simultaneous n- and p-type doped bipolar devices.
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http://dx.doi.org/10.1021/acsami.1c10616DOI Listing
September 2021

Using micro computed tomographic imaging for analyzing kidney stones.

C R Chim 2021 29;24(Suppl 2). Epub 2021 Jun 29.

CNRS, ICP, Bat349, Université Paris-11, 91405 Orsay, France.

Stone analysis is a critical part of the clinical characterization of urolithiasis. This article reviews the strengths and limitations of micro CT in the analysis of stones. Using micro CT alone in a series of 757 stone specimens, micro CT identified the 458 majority calcium oxalate specimens with a sensitivity of 99.6% and specificity of 95.3%. Micro CT alone was also successful in identifying majority apatite, brushite, uric acid, and struvite stones. For some minor minerals-such as apatite in calcium oxalate or calcium salts in uric acid stones-micro CT enables the detection of minute quantities well below 1%. The addition of a standard for calibrating X-ray attenuation values improves the ability of micro CT to identify common stone minerals. The three-dimensional nature of micro CT also allows for the visualization of surface features in stones, which is valuable for the study of stone formation.
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http://dx.doi.org/10.5802/crchim.89DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312732PMC
June 2021

Postnatal development alters functional compartmentalization of myosin light chain kinase in ovine carotid arteries.

Am J Physiol Regul Integr Comp Physiol 2021 Sep 28;321(3):R441-R453. Epub 2021 Jul 28.

Division of Physiology, Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California.

The rate-limiting enzyme for vascular contraction, myosin light chain kinase (MLCK), phosphorylates regulatory myosin light chain (MLC) at rates that appear faster despite lower MLCK abundance in fetal compared with adult arteries. This study explores the hypothesis that greater apparent tissue activity of MLCK in fetal arteries is due to age-dependent differences in intracellular distribution of MLCK in relation to MLC. Under optimal conditions, common carotid artery homogenates from nonpregnant adult female sheep and near-term fetuses exhibited similar values of and for MLCK. A custom-designed, computer-controlled apparatus enabled electrical stimulation and high-speed freezing of arterial segments at exactly 0, 1, 2, and 3 s, calculation of in situ rates of MLC phosphorylation, and measurement of time-dependent colocalization between MLCK and MLC. The in situ rate of MLC phosphorylation divided by total MLCK abundance averaged to values 147% greater in fetal (1.06 ± 0.28) than adult (0.43 ± 0.08) arteries, which corresponded, respectively, to 43 ± 10% and 31 ± 3% of the values measured in homogenates. Confocal colocalization analysis revealed in fetal and adult arteries that 33 ± 6% and 20 ± 5% of total MLCK colocalized with pMLC, and that MLCK activation was greater in periluminal than periadventitial regions over the time course of electrical stimulation in both age groups. Together, these results demonstrate that the catalytic activity of MLCK is similar in fetal and adult arteries, but that the fraction of total MLCK in the functional compartment involved in contraction is significantly greater in fetal than adult arteries.
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http://dx.doi.org/10.1152/ajpregu.00293.2020DOI Listing
September 2021

"Trust my morphology", the key message from a kidney stone.

Urolithiasis 2021 10 23;49(5):493-494. Epub 2021 Jul 23.

Department of Internal Medicine, Division of Mineral Metabolism, Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, UT Southwestern Medical Center, Dallas, TX, USA.

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http://dx.doi.org/10.1007/s00240-021-01280-4DOI Listing
October 2021

Positive Engagement with Pets Buffers the Impact of Intimate Partner Violence on Callous-Unemotional Traits in Children.

J Interpers Violence 2021 Jul 18:8862605211028301. Epub 2021 Jul 18.

Virginia Commonwealth University, School of Social Work, Virginia, United States.

Childhood exposure to intimate partner violence (IPV) is associated with serious psychological outcomes including increased odds of developing callous-unemotional (CU) traits and behaviors. Recent studies suggest that concomitant exposure to animal cruelty (AC) may increase this risk. However, even under these circumstances, bonds with companion animals may still be a protective factor that buffers the deleterious impact of IPV on child adjustment. This cross-sectional study evaluates whether, and to what extent, the association between exposure to IPV and children's CU and empathic-prosocial (EP) traits vary as a function of children's positive engagement with pets and exposure to AC. Participants included 204 children (aged 7-12 years; 57% Latinx) and their maternal caregiver who were recruited from domestic violence agencies in a western US state. We conducted multiple moderation analyses to evaluate each outcome individually (i.e., CU traits, EP traits), adjusting for the effects of child age, gender, and Hispanic ethnicity. Positive engagement with pets significantly moderated the relationship between IPV and CU traits, ∇R = 0.03, (1, 195) = 7.43, = -0.17, (195) = -2.73, = .007. Specifically, when high levels of positive engagement with pets is present, IPV is negatively associated with CU traits, whereas the reverse was true at low levels of positive engagement with pets. Evidence of moderation by AC was not supported. Our findings suggest that children who form close relationships with their pets in the context of IPV appear to derive important support from these animals; safeguarding the well-being of these animals may be critical to their long-term emotional health.
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http://dx.doi.org/10.1177/08862605211028301DOI Listing
July 2021

Association Between Graft Choice and 6-Year Outcomes of Revision Anterior Cruciate Ligament Reconstruction in the MARS Cohort.

Am J Sports Med 2021 08 14;49(10):2589-2598. Epub 2021 Jul 14.

University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Although graft choice may be limited in the revision setting based on previously used grafts, most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome.

Hypothesis: In the ACL revision setting, there would be no difference between autograft and allograft in rerupture rate and patient-reported outcomes (PROs) at 6-year follow-up.

Study Design: Cohort study; Level of evidence, 2.

Methods: Patients who had revision surgery were identified and prospectively enrolled in this cohort study by 83 surgeons over 52 sites. Data collected included baseline characteristics, surgical technique and pathology, and a series of validated PRO measures. Patients were followed up at 6 years and asked to complete the identical set of PRO instruments. Incidence of additional surgery and reoperation because of graft failure were also recorded. Multivariable regression models were used to determine the predictors (risk factors) of PROs, graft rerupture, and reoperation at 6 years after revision surgery.

Results: A total of 1234 patients including 716 (58%) men were enrolled. A total of 325 (26%) underwent revision using a bone-patellar tendon-bone (BTB) autograft; 251 (20%), soft tissue autograft; 289 (23%), BTB allograft; 302 (25%), soft tissue allograft; and 67 (5%), other graft. Questionnaires and telephone follow-up for subsequent surgery information were obtained for 809 (66%) patients, while telephone follow-up was only obtained for an additional 128 patients for the total follow-up on 949 (77%) patients. Graft choice was a significant predictor of 6-year Marx Activity Rating Scale scores ( = .024). Specifically, patients who received a BTB autograft for revision reconstruction had higher activity levels than did patients who received a BTB allograft (odds ratio [OR], 1.92; 95% CI, 1.25-2.94). Graft rerupture was reported in 5.8% (55/949) of patients by their 6-year follow-up: 3.5% (16/455) of patients with autografts and 8.4% (37/441) of patients with allografts. Use of a BTB autograft for revision resulted in patients being 4.2 times less likely to sustain a subsequent graft rupture than if a BTB allograft were utilized ( = .011; 95% CI, 1.56-11.27). No significant differences were found in graft rerupture rates between BTB autograft and soft tissue autografts ( = .87) or between BTB autografts and soft tissue allografts ( = .36). Use of an autograft was found to be a significant predictor of having fewer reoperations within 6 years compared with using an allograft ( = .010; OR, 0.56; 95% CI, 0.36-0.87).

Conclusion: BTB and soft tissue autografts had a decreased risk in graft rerupture compared with BTB allografts. BTB autografts were associated with higher activity level than were BTB allografts at 6 years after revision reconstruction. Surgeons and patients should consider this information when choosing a graft for revision ACL reconstruction.
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http://dx.doi.org/10.1177/03635465211027170DOI Listing
August 2021

Neonatal presentation of PHACE syndrome.

BMJ Case Rep 2021 Jul 12;14(7). Epub 2021 Jul 12.

Department of Neonatal Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1136/bcr-2021-244183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276169PMC
July 2021

Identification of KMT2A-ARHGEF12 fusion in a child with a high-grade B-cell lymphoma.

Cancer Genet 2021 Jun 27;258-259:23-26. Epub 2021 Jun 27.

ARUP Laboratories, Salt Lake City, UT, United States; Department of Pathology, University of Utah, Salt Lake City, UT, United States. Electronic address:

Rearrangements involving KMT2A are common in de novo and therapy-related acute myeloid and lymphoblastic leukemias. There is a diverse recombinome associated with KMT2A involving at least 135 partner genes, with more being discovered due to advances in molecular genetic diagnostics. KMT2A-ARHGEF12 fusion has only rarely been reported, in five cases of acute leukemia and a single case of high-grade B-cell lymphoma. We present a 12-year-old boy with high-grade B-cell lymphoma and KMT2A-ARHGEF12 fusion, whose clinical, morphologic, phenotypic and genotypic profile is strikingly similar to the other case of high grade B cell lymphoma, both otherwise perfectly mimicking Burkitt lymphoma.
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http://dx.doi.org/10.1016/j.cancergen.2021.06.006DOI Listing
June 2021

Reply.

Clin Gastroenterol Hepatol 2021 Jun 29. Epub 2021 Jun 29.

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

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http://dx.doi.org/10.1016/j.cgh.2021.06.033DOI Listing
June 2021

SUN-MKL1 Crosstalk Regulates Nuclear Deformation and Fast Motility of Breast Carcinoma Cells in Fibrillar ECM Microenvironment.

Cells 2021 Jun 19;10(6). Epub 2021 Jun 19.

Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Aligned collagen fibers provide topography for the rapid migration of single tumor cells (streaming migration) to invade the surrounding stroma, move within tumor nests towards blood vessels to intravasate and form distant metastases. Mechanisms of tumor cell motility have been studied extensively in the 2D context, but the mechanistic understanding of rapid single tumor cell motility in the in vivo context is still lacking. Here, we show that streaming tumor cells in vivo use collagen fibers with diameters below 3 µm. Employing 1D migration assays with matching in vivo fiber dimensions, we found a dependence of tumor cell motility on 1D substrate width, with cells moving the fastest and the most persistently on the narrowest 1D fibers (700 nm-2.5 µm). Interestingly, we also observed nuclear deformation in the absence of restricting extracellular matrix pores during high speed carcinoma cell migration in 1D, similar to the nuclear deformation observed in tumor cells in vivo. Further, we found that actomyosin machinery is aligned along the 1D axis and actomyosin contractility synchronously regulates cell motility and nuclear deformation. To further investigate the link between cell speed and nuclear deformation, we focused on the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex proteins and SRF-MKL1 signaling, key regulators of mechanotransduction, actomyosin contractility and actin-based cell motility. Analysis of The Cancer Genome Atlas dataset showed a dramatic decrease in the LINC complex proteins SUN1 and SUN2 in primary tumor compared to the normal tissue. Disruption of LINC complex by SUN1 + 2 KD led to multi-lobular elongated nuclei, increased tumor cell motility and concomitant increase in F-actin, without affecting Lamin proteins. Mechanistically, we found that MKL1, an effector of changes in cellular G-actin to F-actin ratio, is required for increased 1D motility seen in SUN1 + 2 KD cells. Thus, we demonstrate a previously unrecognized crosstalk between SUN proteins and MKL1 transcription factor in modulating nuclear shape and carcinoma cell motility in an in vivo relevant 1D microenvironment.
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http://dx.doi.org/10.3390/cells10061549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234170PMC
June 2021

Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension.

Clin Gastroenterol Hepatol 2021 Jun 26. Epub 2021 Jun 26.

Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Background & Aims: We evaluated treatment withdrawal, long-term outcomes, and safety of budesonide oral suspension (BOS) 2.0 mg twice daily in patients with eosinophilic esophagitis who completed a 12-week induction study.

Methods: Induction full responders (≤6 eosinophils per high-power field [eos/hpf] and ≥30% reduction in the Dysphagia Symptom Questionnaire score) to BOS 2.0 mg twice daily (ORBIT1/SHP621-301/NCT02605837) were randomized to continue BOS (BOS-BOS) or withdraw to placebo (BOS-PBO) for 36 weeks (ORBIT2/SHP621-302/NCT02736409). Induction partial responders and nonresponders, and patients who received induction placebo, received BOS for 36 weeks. The primary end point was the proportion of BOS-BOS and BOS-PBO patients who relapsed (≥15 eos/hpf and ≥4 days of dysphagia [Dysphagia Symptom Questionnaire] over 2 weeks) by week 36. The key secondary end point was the proportion of induction partial responders and nonresponders who fully responded after 52 weeks of total BOS therapy. Secondary end points included the following: proportion of induction full responders with histologic responses (≤1, ≤6, <15 eos/hpf) at week 12 of the extension study, and safety outcomes.

Results: The randomized withdrawal period enrolled 48 patients (BOS-BOS, n = 25; BOS-PBO, n = 23); 106 induction partial responders and nonresponders, and 65 induction placebo patients received BOS. More BOS-PBO than BOS-BOS patients relapsed over 36 weeks (43.5% vs 24.0%; P = .131) and had histologic responses at week 12 of therapy (P < .001). Overall, 13.2% of induction partial responders and nonresponders fully responded at week 36. BOS was well tolerated; therapy duration was not associated with new safety concerns.

Conclusions: For induction full responders, continuing BOS numerically improved maintenance of efficacy vs withdrawal. A longer therapy duration did not raise safety concerns. (ClinicalTrials.gov: NCT02736409.).
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http://dx.doi.org/10.1016/j.cgh.2021.06.020DOI Listing
June 2021

Human jackstone arms show a protein-rich, X-ray lucent core, suggesting that proteins drive their rapid and linear growth.

Urolithiasis 2021 Jun 6. Epub 2021 Jun 6.

Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.

Jackstone calculi, having arms that extend out from the body of the stone, were first described over a century ago, but this morphology of stones has been little studied. We examined 98 jackstones from 50 different patient specimens using micro-computed tomography (micro CT) and infrared (IR) spectroscopy. Micro CT showed that jackstone arms consisted of an X-ray lucent core within each arm. This X-ray lucent core frequently showed sporadic, thin layers of apatite arranged transversely to the axis of the arm. The shells of the jackstones were always composed of calcium oxalate (CaOx), and with the monohydrate form the majority or sole mineral. Study of layering in the shell regions by micro CT showed that growth lines extended from the body of the stone out onto jack arms and that the thickness of the shell covering of jack arms often thinned with distance from the stone body, suggesting that the arms grew at a faster radial rate than did the stone body. Histological cross-sections of decalcified jackstone arms showed the core to be more highly autofluorescent than was the CaOx shell, and immunohistochemistry showed the core to be enriched in Tamm-Horsfall protein. We hypothesize that the protein-rich core of a jack arm might preferentially bind more protein from the urine and resist deposition of CaOx, such that the arm grows in a linear manner and at a faster rate than the bulk of the stone. This hypothesis thus predicts an enrichment of certain urine proteins in the core of the jack arm, a theory that is testable by appropriate analysis.
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http://dx.doi.org/10.1007/s00240-021-01275-1DOI Listing
June 2021

Human kidney stones: a natural record of universal biomineralization.

Nat Rev Urol 2021 Jul 24;18(7):404-432. Epub 2021 May 24.

Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

GeoBioMed - a new transdisciplinary approach that integrates the fields of geology, biology and medicine - reveals that kidney stones composed of calcium-rich minerals precipitate from a continuum of repeated events of crystallization, dissolution and recrystallization that result from the same fundamental natural processes that have governed billions of years of biomineralization on Earth. This contextual change in our understanding of renal stone formation opens fundamentally new avenues of human kidney stone investigation that include analyses of crystalline structure and stratigraphy, diagenetic phase transitions, and paragenetic sequences across broad length scales from hundreds of nanometres to centimetres (five Powers of 10). This paradigm shift has also enabled the development of a new kidney stone classification scheme according to thermodynamic energetics and crystalline architecture. Evidence suggests that ≥50% of the total volume of individual stones have undergone repeated in vivo dissolution and recrystallization. Amorphous calcium phosphate and hydroxyapatite spherules coalesce to form planar concentric zoning and sector zones that indicate disequilibrium precipitation. In addition, calcium oxalate dihydrate and calcium oxalate monohydrate crystal aggregates exhibit high-frequency organic-matter-rich and mineral-rich nanolayering that is orders of magnitude higher than layering observed in analogous coral reef, Roman aqueduct, cave, deep subsurface and hot-spring deposits. This higher frequency nanolayering represents the unique microenvironment of the kidney in which potent crystallization promoters and inhibitors are working in opposition. These GeoBioMed insights identify previously unexplored strategies for development and testing of new clinical therapies for the prevention and treatment of kidney stones.
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http://dx.doi.org/10.1038/s41585-021-00469-xDOI Listing
July 2021

Development, implementation, and use of an "equity lens" integrated into an institutional quality scorecard.

J Am Med Inform Assoc 2021 07;28(8):1785-1790

Section of General Internal Medicine, Biological Sciences Division, University of Chicago, Chicago, Illinois, USA.

Few healthcare provider organizations systematically track their healthcare equity, and fewer enable direct interaction with such data by their employees. From May to August 2019, we enhanced the data architecture and reporting functionality of our existing institutional quality scorecard to allow direct comparisons of quality measure performance by gender, age, race, ethnicity, language, zip code, and payor. The Equity Lens was made available to over 4000 staff in September 2019 for 82 institutional quality measures. During the first 11 months, 235 unique individuals used the tool; users were most commonly from the quality and equity departments. Two early use cases evaluated hypertension control and readmissions by race, identifying potential inequities. This is the first description of an interactive equity lens integrated into an institutional quality scorecard made available to healthcare system employees. Early evidence suggests the tool is used and can inform quality improvement initiatives.
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http://dx.doi.org/10.1093/jamia/ocab082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324221PMC
July 2021

Do Narcotic Use, Physical Therapy Location, or Payer Type Predict Patient-Reported Outcomes After Anterior Cruciate Ligament Reconstruction?

Orthop J Sports Med 2021 Apr 26;9(4):2325967121994833. Epub 2021 Apr 26.

Investigation performed at Cleveland Clinic, Cleveland, Ohio, USA.

Background: Opioid use and public insurance have been correlated with worse outcomes in a number of orthopaedic surgeries. These factors have not been investigated with anterior cruciate ligament reconstruction (ACLR).

Purpose/hypothesis: To evaluate if narcotic use, physical therapy location, and insurance type are predictors of patient-reported outcomes after ACLR. It was hypothesized that at 1 year postsurgically, increased postoperative narcotic use would be associated with worse outcomes, physical therapy obtained within the authors' integrated health care system would lead to better outcomes, and public insurance would lead to worse outcomes and athletic activity.

Study Design: Cohort study; Level of evidence, 2.

Methods: All patients undergoing unilateral, primary ACLR between January 2015 and February 2016 at a large health system were enrolled in a standard-of-care prospective cohort. Knee injury and Osteoarthritis Score (KOOS) and the Hospital for Special Surgery Pediatric-Functional Activity Brief Scale (HSS Pedi-FABS) were collected before surgery and at 1 year postoperatively. Concomitant knee pathology was assessed arthroscopically and electronically captured. Patient records were analyzed to determine physical therapy location, insurance status, and narcotic use. Multivariable regression analyses were used to identify significant predictors of the KOOS and HSS Pedi-FABS score.

Results: A total of 258 patients were included in the analysis (mean age, 25.8; 51.2% women). In multivariable regression analysis, narcotic use, physical therapy location, and insurance type were not independent predictors of any KOOS subscales. Public insurance was associated with a lower HSS Pedi-FABS score (-4.551, = .047) in multivariable analysis. Narcotic use or physical therapy location was not associated with the HSS Pedi-FABS score.

Conclusion: Increased narcotic use surrounding surgery, physical therapy location within the authors' health care system, and public versus private insurance were not associated with disease-specific KOOS subscale scores. Patients with public insurance had worse HSS Pedi-FABS activity scores compared with patients with private insurance, but neither narcotic use nor physical therapy location was associated with activity scores. Physical therapy location did not influence outcomes, suggesting that patients be given a choice in the location they received physical therapy (as long as a standardized protocol is followed) to maximize compliance.
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http://dx.doi.org/10.1177/2325967121994833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085373PMC
April 2021

Mental health and wellbeing implications of the COVID-19 quarantine for disabled and disadvantaged children and young people: evidence from a cross-cultural study in Zambia and Sierra Leone.

BMC Psychol 2021 May 15;9(1):79. Epub 2021 May 15.

School of Business and Law, University of East London, London, UK.

Background: The mental health impact of the COVID-19 pandemic and quarantining on children and young people (CYP) living in low- and middle-income countries (LMICs) has yet to be fully comprehended. CYP in LMICs are at utmost risk, given the COVID-19-related restrictions and social distancing measures, resulting in reduced access to school-based services for nutritional and mental health needs. This study examined mental health of CYP during the first COVID-19 lockdown in Zambia and Sierra Leone.

Method: A total of 468 disabled and disadvantaged CYP aged 12 to 25 completed a planning tool that comprised the short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), as well as open-ended questions covering social connectedness, physical distancing and educational challenges during the lockdown. The community coaches screened individuals and families who could be eligible to receive emergency aid, and based on a convenience sample following distribution of aid, recipients were invited to complete the planning tool.

Results: The data showed that participants in the global south have increasing anxieties and fears centred on accessing offline educational resources and income loss in the family effecting food security and their ability to return to education. Mean (SD) SWEMWBS scores for all participants in Zambia and Sierra Leone, were 19.61 (3.45) and 21.65 (2.84), respectively. Mental well-being scores were lower in females, children aged 12-14 and participants with two or more disabilities. Factors significantly associated with poor mental wellbeing in the sample were: type of disability, nationality, peer relationships, connection to others during the pandemic, knowledge about COVID-19, worry about the long-term impact of COVID-19, and the types of self-isolating.

Conclusion: The study shows that participants who self-reported low levels of COVID-19 health literacy also scored low on the mental wellbeing self-assessment. Yet, despite undoubted limited resources, these CYP are doing well in identifying their needs and maintaining hope in the face of the problems associated with COVID-19 in countries where stigma persists around mental ill-health.
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http://dx.doi.org/10.1186/s40359-021-00583-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123096PMC
May 2021

Impact of natalizumab on quality of life in a real-world cohort of patients with multiple sclerosis: Results from MS PATHS.

Mult Scler J Exp Transl Clin 2021 Apr-Jun;7(2):20552173211004634. Epub 2021 Apr 15.

Biogen, Cambridge, MA, USA, at the time of these analyses.

Background: Optimizing multiple sclerosis treatment warrants understanding of changes in physical, mental, and social health.

Objective: To assess the impact of natalizumab on Quality of Life in Neurological Disorders (Neuro-QoL) scores.

Methods: Annualized change in T-scores and likelihood of ≥5-point improvement over baseline were calculated for each Neuro-QoL domain after natalizumab initiation. Comparisons with ocrelizumab-treated patients were conducted after propensity score weighting and adjustment for relevant co-medications, year, and drug-year interaction.

Results: Among 164 natalizumab patients analyzed, 8 of 12 Neuro-QoL domains improved significantly, with greater improvement in patients with abnormal baseline Neuro-QoL. In the subgroup comparison of natalizumab-treated ( = 145) and ocrelizumab-treated ( = 520) patients, significant improvement occurred in 9 of 12 and 4 of 12 domains, respectively. The difference between groups was statistically significant for positive affect and well-being ( = 0.02), sleep ( = 0.003), and satisfaction with social roles and activities (SRA) ( = 0.03) in the overall population and for emotional and behavioral dyscontrol ( = 0.01), participation in SRA ( = 0.0001), and satisfaction with SRA ( = 0.02) in patients with abnormal baseline Neuro-QoL.

Conclusions: Natalizumab can produce clinically meaningful improvements in mental and social health. Such improvements are unlikely to be primarily driven by expectation bias, as their magnitude exceeded improvements with another high-efficacy therapy, ocrelizumab.
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http://dx.doi.org/10.1177/20552173211004634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053767PMC
April 2021

Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial.

Clin Gastroenterol Hepatol 2021 Apr 19. Epub 2021 Apr 19.

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background & Aims: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease for which there is currently no pharmacologic therapy approved by the US Food and Drug Administration.

Methods: In this double-blind, placebo-controlled, phase 3 trial, patients 11-55 years of age with EoE and dysphagia were randomized 2:1 to receive budesonide oral suspension (BOS) 2.0 mg twice daily or placebo for 12 weeks at academic or community care practices. Co-primary endpoints were the proportion of stringent histologic responders (≤6 eosinophils/high-power field) or dysphagia symptom responders (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] score) over 12 weeks. Changes in DSQ score (key secondary endpoint) and EoE Endoscopic Reference Score (EREFS) (secondary endpoint) from baseline to week 12, and safety parameters were examined.

Results: Overall, 318 patients (BOS, n = 213; placebo, n = 105) were randomized and received ≥1 dose of study treatment. More BOS-treated than placebo-treated patients achieved a stringent histologic response (53.1% vs 1.0%; Δ52% [95% confidence interval (CI), 43.3%-59.1%]; P < .001) or symptom response (52.6% vs 39.1%; Δ13% [95% CI, 1.6%-24.3%]; P = .024) over 12 weeks. BOS-treated patients also had greater improvements in least-squares mean DSQ scores and EREFS over 12 weeks than placebo-treated patients: DSQ, -13.0 (SEM 1.2) vs -9.1 (SEM 1.5) (Δ-3.9 [95% CI, -7.1 to -0.8]; P = .015); EREFS, -4.0 (SEM 0.3) vs -2.2 (SEM 0.4) (Δ-1.8 [95% CI, -2.6 to -1.1]; P < .001). BOS was well tolerated; most adverse events were mild or moderate in severity.

Conclusions: In patients with EoE, BOS 2.0 mg twice daily was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks. BOS 2.0 mg twice daily was well tolerated. ClinicalTrials.gov number: NCT02605837.
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http://dx.doi.org/10.1016/j.cgh.2021.04.022DOI Listing
April 2021

A deepening understanding of animal culture suggests lessons for conservation.

Proc Biol Sci 2021 04 21;288(1949):20202718. Epub 2021 Apr 21.

Sea Mammal Research Unit, School of Biology, University of St Andrews, St Andrews KY16 8LB, UK.

A key goal of conservation is to protect biodiversity by supporting the long-term persistence of viable, natural populations of wild species. Conservation practice has long been guided by genetic, ecological and demographic indicators of risk. Emerging evidence of animal culture across diverse taxa and its role as a driver of evolutionary diversification, population structure and demographic processes may be essential for augmenting these conventional conservation approaches and decision-making. Animal culture was the focus of a ground-breaking resolution under the Convention on the Conservation of Migratory Species of Wild Animals (CMS), an international treaty operating under the UN Environment Programme. Here, we synthesize existing evidence to demonstrate how social learning and animal culture interact with processes important to conservation management. Specifically, we explore how social learning might influence population viability and be an important resource in response to anthropogenic change, and provide examples of how it can result in phenotypically distinct units with different, socially learnt behavioural strategies. While identifying culture and social learning can be challenging, indirect identification and parsimonious inferences may be informative. Finally, we identify relevant methodologies and provide a framework for viewing behavioural data through a cultural lens which might provide new insights for conservation management.
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http://dx.doi.org/10.1098/rspb.2020.2718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059593PMC
April 2021

Measured Resection Techniques Do Not Align to the Cylindrical Axis in Kinematic Total Knee Arthroplasty.

Arthroplast Today 2021 Apr 23;8:157-162. Epub 2021 Mar 23.

Orthopaedic Department, Westmead Hospital, Westmead, New South Wales, Australia.

Background: There has been increasing interest with improved functional results in kinematically aligned total knee arthroplasty. Kinematic alignment seeks to replicate the rotational axes of the individual knee. The femoral component can either be aligned to the estimated prearthritic distal and posterior joint lines via a measured-resection technique or by aligning to the cylindrical axis (CA). The CA is calculated using three-dimensional imaging and defined as a line equidistant from the medial and lateral condylar surfaces from 15° to 115° flexion. This study investigates whether these 2 techniques lead to similar alignment angles in the coronal plane.

Materials And Methods: One hundred three knees undergoing total knee arthroplasty were assessed using a computed tomography-based protocol. The image-based cylindrical axis coronal angle (CAA) was calculated, and the distal condylar coronal angle (DCA) was calculated to simulate a caliper measured resection technique. A computed tomographic planning software program was used to measure the offset from the distal-most extent of the calculated cylinder to the distal-most aspect of the condyles.

Results: The DCA measured 3.3° valgus (standard deviation 2.4°) and the CAA 1.8° valgus (standard deviation 2.1°). The mean difference in offset from CAA radius to DCA from the medial condyle and the lateral condyle was 2.85 mm and 1.51 mm, respectively, increasing valgus predilection.

Conclusions: Caliper measured resection kinematically aligned techniques will position the femoral component in a significantly more valgus position than when aligning to the CA of the knee. This is due to an increased offset of the distal femoral articulation from the most distal aspect of the cylinder on the medial side of the knee.
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http://dx.doi.org/10.1016/j.artd.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994728PMC
April 2021

Antibodies to neutralising epitopes synergistically block the interaction of the receptor-binding domain of SARS-CoV-2 to ACE 2.

Clin Transl Immunology 2021 7;10(3):e1260. Epub 2021 Mar 7.

Institute for Glycomics Griffith University Gold Coast QLD Australia.

Objectives: A major COVID-19 vaccine strategy is to induce antibodies that prevent interaction between the Spike protein's receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2). These vaccines will also induce T-cell responses. However, concerns were raised that aberrant vaccine-induced immune responses may exacerbate disease. We aimed to identify minimal epitopes on the RBD that would induce antibody responses that block the interaction of the RBD and ACE2 as a strategy leading to an effective vaccine with reduced risk of inducing immunopathology.

Methods: We procured a series of overlapping 20-amino acid peptides spanning the RBD and asked which were recognised by plasma from COVID-19 convalescent patients. Identified epitopes were conjugated to diphtheria-toxoid and used to vaccinate mice. Immune sera were tested for binding to the RBD and for their ability to block the interaction of the RBD and ACE2.

Results: Seven putative vaccine epitopes were identified. Memory B-cells (MBCs) specific for one of the epitopes were identified in the blood of convalescent patients. When used to vaccinate mice, six induced antibodies that bound recRBD and three induced antibodies that could partially block the interaction of the RBD and ACE2. However, when the sera were combined in pairs, we observed significantly enhanced inhibition of binding of RBD to ACE2. Two of the peptides were located in the main regions of the RBD known to contact ACE2. Of significant importance to vaccine development, two of the peptides were in regions that are invariant in the UK and South African strains.

Conclusion: COVID-19 convalescent patients have SARS-CoV-2-specific antibodies and MBCs, the specificities of which can be defined with short peptides. Epitope-specific antibodies synergistically block RBD-ACE2 interaction.
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http://dx.doi.org/10.1002/cti2.1260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937407PMC
March 2021

Acute appendiceal diverticulitis: a case report.

Radiol Case Rep 2021 May 24;16(5):1072-1074. Epub 2021 Feb 24.

Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905 USA.

Acute appendiceal diverticulitis is a difficult prospective diagnosis due to both its rarity and clinical overlap with other ileocecal diseases, such as acute appendicitis. Few preoperative radiological images of acute appendiceal diverticulitis have been presented in the literature. We report a case of acute appendiceal diverticulitis initially diagnosed with outpatient ultrasound and confirmed with contrast-enhanced computed tomography in an 85-year-old male who presented with right lower quadrant pain. Appendiceal diverticulitis is an often overlooked diagnosis, and given its association with appendiceal neoplasms and relatively high rate of perforation, it is important to consider this entity in patients with right lower quadrant pain in order to ensure that they are managed appropriately. The addition of high quality ultrasound and computed tomography (CT) images to the literature may heighten awareness of this rare condition and facilitate accurate preoperative diagnosis and management in these patients.
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http://dx.doi.org/10.1016/j.radcr.2021.02.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921191PMC
May 2021

Initial experience of the High-Density Grid catheter in patients undergoing catheter ablation for atrial fibrillation.

J Interv Card Electrophysiol 2021 Feb 27. Epub 2021 Feb 27.

Electrophysiology Department, Barts Heart Centre, St. Bartholomew's Hospital, London, UK.

Purpose: A significant proportion of patients undergoing catheter ablation for atrial fibrillation (AF) experience arrhythmia recurrence. This is mostly due to pulmonary vein reconnection (PVR). Whether mapping using High-Density Wave (HDW) technology is superior to standard bipolar (SB) configuration at detecting PVR is unknown. We aimed to evaluate the efficacy of HDW technology compared to SB mapping in identifying PVR.

Methods: High-Density (HD) multipolar Grid catheters were used to create left atrial geometries and voltage maps in 36 patients undergoing catheter ablation for AF (either due to recurrence of an atrial arrhythmia from previous AF ablation or de novo AF ablation). Nineteen SB maps were also created and compared. Ablation was performed until pulmonary vein isolation was achieved.

Results: Median time of mapping with HDW was 22.3 [IQR: 8.2] min. The number of points collected with HDW (13299.6±1362.8 vs 6952.8±841.9, p<0.001) and used (2337.3±158.0 vs 1727.5±163.8, p<0.001) was significantly higher compared to SB. Moreover, HDW was able to identify more sleeves (16 for right and 8 for left veins), where these were confirmed electrically silent by SB, with significantly increased PVR sleeve size as identified by HDW (p<0.001 for both right and left veins). Importantly, with the use of HDW, the ablation strategy changed in 23 patients (64% of targeted veins) with a significantly increased number of lesions required as compared to SB for right (p=0.005) and left veins (p=0.003).

Conclusion: HDW technology is superior to SB in detecting pulmonary vein reconnections. This could potentially result into a significant change in ablation strategy and possibly to increased success rate following pulmonary vein isolation.
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http://dx.doi.org/10.1007/s10840-021-00950-yDOI Listing
February 2021

Phase I study of JAK1/2 inhibitor ruxolitinib with weekly paclitaxel for the treatment of HER2-negative metastatic breast cancer.

Cancer Chemother Pharmacol 2021 05 14;87(5):673-679. Epub 2021 Feb 14.

Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.

Purpose: Preclinical studies support the JAK2-STAT3 signaling pathway as a key driver in CD44+ CD24- "stem-cell-like" breast cancer cells. Ruxolitinib is an orally bioavailable JAK1/2 inhibitor. We aimed to identify the recommended phase 2 dose (RP2D) of ruxolitinib in combination with paclitaxel in patients with HER2-negative metastatic breast cancer (MBC).

Methods: Eligible patients had HER2-negative MBC and had received ≤ 3 chemotherapy regimens for advanced disease. Patients received oral ruxolitinib (10-25 mg bid) in a 3 + 3 dose escalation design in combination with weekly paclitaxel 80 mg/m in a 3-week cycle. The primary objective was to determine the maximum tolerated dose (MTD) and the RP2D.

Results: Nineteen patients received protocol therapy (mean age 52 years). Eight (42%) had triple-negative breast cancer and 11 (58%) had hormone receptor-positive disease; 12 (63%) had visceral disease. Ten (53%) patients had not received prior treatment for advanced disease. Patients received a median number of 5 cycles of combination therapy (range 1-12) and five patients continued single-agent ruxolitinib. The MTD of ruxolitinib was 25 mg bid when combined with paclitaxel, and the RP2D for the combination was 15 mg bid. Thirteen (68%) patients required dose reductions or holds. Most frequent toxicities reported of any grade were neutropenia (50%) and anemia (33%). There were no grade 4/5 toxicities attributed to study drug. Four (21%) patients had PR, 12 (63%) had SD and three (16%) had PD as their best response.

Conclusion: The combination of ruxolitinib and weekly paclitaxel was well tolerated with evidence of clinical activity. Further analysis of this combination is ongoing (NCT02041429).

Trial Registration: NCT02041429. Date of registration: January 22, 2014.
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http://dx.doi.org/10.1007/s00280-021-04245-xDOI Listing
May 2021

Renal Protection Phenomenon Observed in a Porcine Model After Electromagnetic Lithotripsy Using a Treatment Pause.

J Endourol 2021 05 22;35(5):682-686. Epub 2021 Feb 22.

Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Pretreating the kidney with 100 low-energy shock waves (SWs) with a time pause before delivering a clinical dose of SWs (Dornier HM-3, 2000 SWs, 24 kV, and 120 SWs/min) has been shown to significantly reduce the size of the hemorrhagic lesion produced in that treated kidney, compared to a protocol without pretreatment. It has been assumed that a similar reduction in injury will occur with lithotripters other than the HM-3, but experiments to confirm this assumption are lacking. In this study, we sought to verify that the lesion protection phenomenon also occurs in a lithotripter using an electromagnetic shock source and dry-head coupling. Eleven female pigs were placed in a Dornier Compact S lithotripter where the left kidney of each animal was targeted for lithotripsy treatment. Some kidneys received 2500 SWs at power level (PL) = 5 (120 SWs/min) while some kidneys were pretreated with 100 SWs at PL = 1, with a 3-minute time pause, followed immediately by 2500 SWs at PL = 5 (120 SWs/min). Lesion size analysis was performed to assess the volume of hemorrhagic tissue injury created by each treatment regimen (% functional renal volume). Lesion size fell by 85% ( = 0.01) in the 100 SW pretreatment group compared to the injury produced by a regimen without pretreatment. The results suggest that the treatment pause protection phenomenon occurs with a Dornier Compact S, a machine distinctly different from the Dornier HM-3. This result also suggests that this phenomenon may be observed generally in SW lithotripters.
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http://dx.doi.org/10.1089/end.2020.0681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147507PMC
May 2021

Limitations of Available Blood Products for Massive Transfusion During Mass Casualty Events at us Level 1 Trauma Centers.

Shock 2021 Jan 14. Epub 2021 Jan 14.

The Center for Translational Injury Research the Departments of Surgery Duke University Pratt School of Engineering Pathology and Laboratory Medicine Emergency Medicine, The McGovern Medical School at the University of Texas Health Science Center, Houston, Texas The Red Duke Trauma Institute at Memorial Hermann Hospital, Texas Medical Center, Houston, Texas, Department of Surgery Vanderbilt University School of Medicine, Nashville, TN, Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, UK Department of Surgery, University of California Riverside, Riverside, California, USA VCU Surgery Trauma, Critical Care and Emergency Surgery, Richmond, Virginia, USA Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, The Ottawa Hospital, Civic Campus, Ottawa, Ontario, Canada Department of Cardiothoracic and Vascular Surgery, Faculty of Life Science Örebro University Hospital and University, Örebro, Sweden Vascular Surgery Service, San Antonio Military Medical Center, San Antonio, Texas, USA Regional Trauma Services Foothills Medical Centre; Departments of Surgery, Critical Care Medicine, University of Calgary, Calgary, Alberta; Canadian Forces Health Services Fundación Valle del Lili, Division of Trauma and Acute Care Surgery, Department of Surgery. Universidad del Valle, Colombia Department of Surgery and Surgical Critical Care, University of Campinas, Campinas, Brazil Department of Cardiothoracic and Vascular Surgery, Linköping University Hospital, Linköping, Sweden Division Chief Acute Care Surgery, Department of Surgery Tulane, New Orleans, Louisiana, USA.

Introduction: Exsanguination remains a leading cause of preventable death in traumatically injured patients. To better treat hemorrhagic shock, hospitals have adopted massive transfusion protocols (MTPs) which accelerate the delivery of blood products to patients. There has been an increase in mass casualty events (MCE) worldwide over the past two decades. These events can overwhelm a responding hospital's supply of blood products. Using a computerized model, this study investigated the ability of US trauma centers (TCs) to meet the blood product requirements of MCEs.

Methods: Cross-sectional survey data of on-hand blood products were collected from 16 US level-1 TCs. A discrete event simulation model of a TC was developed based on historic data of blood product consumption during MCEs. Each hospital's blood bank was evaluated across increasingly more demanding MCEs using modern MTPs to guide resuscitation efforts in massive transfusion (MT) patients.

Results: A total of 9,000 simulations were performed on each TC's data. Under the least demanding MCE scenario, the median size MCE in which TCs failed to adequately meet blood product demand was 50 patients (IQR 20-90), considering platelets. 10 TCs exhaust their supply of platelets prior to RBCs or plasma. Disregarding platelets, five TCs exhausted their supply of O- packed red blood cells (RBCs), six exhausted their AB plasma supply, and five had a mixed exhaustion picture.

Conclusion: Assuming a TC's ability to treat patients is limited only by their supply of blood products, US level-1 TCs lack the on-hand blood products required to adequately treat patients following a MCE. Use of non-traditional blood products, that have a longer shelf life, may allow TCs to better meet the blood product requirement needs of patients following larger MCEs.
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http://dx.doi.org/10.1097/SHK.0000000000001719DOI Listing
January 2021
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