Publications by authors named "Jonathan Nguyen"

61 Publications

Correlating Immune Cell Infiltration Patterns with Recurrent Somatic Mutations in Advanced Clear Cell Renal Cell Carcinoma.

Eur Urol Focus 2021 May 11. Epub 2021 May 11.

Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Integrated Mathematical Oncology Department, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Background: Clear cell renal cell carcinoma (ccRCC) tumors have low frequencies of genetic alterations compared with other malignancies, but very high levels of immune cell infiltration and favorable response rates to immunotherapy. Currently, the interplay between specific ccRCC somatic mutations and immune infiltration pattern is unclear.

Objective: To analyze the associations between common ccRCC somatic mutations and immune cell infiltration patterns within the tumor immune microenvironment (TIME).

Design, Setting, And Participants: The study included tumor samples (24 primary and 24 metastatic) from 48 patients with stage IV ccRCC. Targeted sequencing was performed for well-characterized recurrent somatic mutations in ccRCC, with the analysis focusing on the six most common ones: VHL, BAP1, PBRM1, SETD2, TP53, and KDM5C. For each sample, multiplex immunofluorescence (IF) was performed in lymphoid and myeloid panels, for seven regions of interest in three zones (tumor core, stroma, and tumor-stroma interface). IF-derived cellular densities were compared across patients, stratified by their somatic mutation status, using a linear mixed-model analysis. External validation was pursued using RNA-seq enrichment scoring from three large external data sources.

Results And Limitations: Tumors with SETD2 mutations demonstrated significantly decreased levels of FOXP3+ T cells in the tumor core, stroma, and tumor-stroma interface. PBRM1 mutations were associated with decreased FOXP3+ T cells in the tumor core. Primary KDM5C mutations were associated with significantly increased CD206+ macrophage tumor infiltration in the tumor core. A computational method estimating immune cell types in the TIME using bulk RNA-seq data, xCell scoring, failed to validate associations from the IF analysis in large external data sets. A major limitation of the study is the relatively small patient population studied.

Conclusions: This study provides evidence that common somatic mutations in ccRCC, such as SETD2, PBRM1, and KDM5C, are associated with distinct immune infiltration patterns within the TIME.

Patient Summary: In this study, we analyzed tumor samples from patients with metastatic kidney cancer to determine whether common genetic mutations that arise from the cancer cells are associated with the density of immune cells found within those tumors. We found several distinct immune cell patterns that were associated with specific genetic mutations. These findings provide insight into the interaction between cancer genetics and the immune system in kidney cancer.
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http://dx.doi.org/10.1016/j.euf.2021.04.014DOI Listing
May 2021

Spatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma.

PLoS One 2021 21;16(4):e0245415. Epub 2021 Apr 21.

Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.

Immune infiltration is typically quantified using cellular density, not accounting for cellular clustering. Tumor-associated macrophages (TAM) activate oncogenic signaling through paracrine interactions with tumor cells, which may be better reflected by local cellular clustering than global density metrics. Using multiplex immunohistochemistry and digital pathologic analysis we quantified cellular density and cellular clustering for myeloid cell markers in 129 regions of interest from 55 samples from 35 patients with metastatic ccRCC. CD68+ cells were found to be clustered with tumor cells and dispersed from stromal cells, while CD163+ and CD206+ cells were found to be clustered with stromal cells and dispersed from tumor cells. CD68+ density was not associated with OS, while high tumor/CD68+ cell clustering was associated with significantly worse OS. These novel findings would not have been identified if immune infiltrate was assessed using cellular density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors. Significance: Increased clustering of CD68+ TAMs and tumor cells was associated with worse overall survival for patients with metastatic ccRCC. This effect would not have been identified if immune infiltrate was assessed using cell density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245415PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059840PMC
April 2021

Effectively Conducting Oncology Clinical Trials During the COVID-19 Pandemic.

Adv Radiat Oncol 2021 May-Jun;6(3):100676. Epub 2021 Mar 3.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: Clinical trial enrollment has declined globally as a result of the coronavirus disease 2019 (COVID-19) pandemic. This underscores the importance of structured methods to continue critical medical research safely and efficiently.

Methods And Materials: We report the effect of a phased trial reopening strategy, remote research staffing, and telemedicine on cancer trial enrollment at one of the largest radiation oncology academic cancer centers. In phase 1, trials investigating definitive therapeutic benefit were opened, followed by trials not increasing patient exposure or pulmonary toxicity risk in phase 2. During phase 2.5, multicenter trials reopened and limited research staff were allowed on site.

Results: Despite initial enrollment declines during the early pandemic, the percentage of new patients enrolling in clinical trials from March to August 2020 was 8.8%, and represented a 10.5% relative increase from 2019. Monthly accrual enrollment from March to August 2019 ranged from 42 to 71, compared with enrollment during COVID-19 from 23 to 73 patients ( < .001).

Conclusions: Through a phased approach to trial reopening and adaptive techniques, the division of radiation oncology maintained cancer trial accrual during the COVID-19 pandemic. The experience may help centers maintain accrual, preserve clinical trial integrity, and minimize risk to patients and staff.
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http://dx.doi.org/10.1016/j.adro.2021.100676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927592PMC
March 2021

The T681I mutation is highly resistant to imatinib and dasatinib and detectable in clinical samples prior to treatment.

Haematologica 2021 Feb 25. Epub 2021 Feb 25.

Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.

Not available.
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http://dx.doi.org/10.3324/haematol.2020.261354DOI Listing
February 2021

Clinical decision making involving prescription drug monitoring programs: A factorial, vignette-based study among student pharmacists.

J Am Pharm Assoc (2003) 2021 May-Jun;61(3):316-324. Epub 2021 Feb 10.

Objectives: Prescription drug monitoring programs (PDMPs) are state-maintained databases that providers may reference when deciding to prescribe or dispense controlled substances. As more states begin to mandate PDMP use at the point of care, it is imperative to assess how pharmacists use PDMP information when determining whether to fill a controlled substance prescription (CSP). The objective of this study was to evaluate which factors affected fourth-year student pharmacists' decision to fill an opioid prescription, their level of confidence in their decision making, and familiarity with the PDMP.

Methods: We used a 2 factorial design to present a series of text-based vignettes to fourth-year student pharmacists. Each participant received 8 vignettes (5 randomly selected, 3 fixed), representing a hypothetical hydrocodone-acetaminophen combination prescription with varying levels of the following dichotomous factors: doctor shopping, dosage, pharmacy shopping, and concurrent benzodiazepine prescription. Participants were asked to decide whether or not they would fill each of the hypothetical prescriptions they received. A multilevel model was used to measure the association between each of the vignette factors, age, race, sex, experience with PDMP, and the decision to refuse to fill a prescription. Each vignette response served as an independent observation.

Results: A total of 87 participants yielded 696 vignette responses. Participants were significantly more likely to refuse to fill prescriptions with doctor shopping (adjusted odds ratio [aOR] 19.86 [95% CI 10.78-36.58]), pharmacy shopping (6.78 [4.13-11.12]), dosage (1.83 [1.16-2.90]), or if the student pharmacist was of female sex (1.73 [1.02-2.93]). Concomitant benzodiazepine use was not associated with a no-fill decision (1.45 [0.92-2.27]).

Conclusion: This study reveals that student pharmacists' decision to fill a prescription is dependent on both prescription characteristics and a patient's CSP history. The importance of PDMP history cannot be downplayed and suggests that PDMP use may be effective in informing patient care decisions. Still, the variability in filling decision highlights the need to teach a formulaic approach to CSP dispensing in colleges of pharmacy.
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http://dx.doi.org/10.1016/j.japh.2021.01.010DOI Listing
February 2021

Challenges of acute care surgery: Ballistic wound through a Bochdalek hernia.

J Trauma Acute Care Surg 2021 05;90(5):e116-e118

From the Department of Surgery (B.P.L., A.A.G., J.D.S.), Emory University; and Department of Surgery (J.H.N.), Morehouse School of Medicine, Atlanta, Georgia.

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http://dx.doi.org/10.1097/TA.0000000000003102DOI Listing
May 2021

Intra-abdominal Inferior Vena Cava Injuries: Operative Strategies and Outcomes.

Am Surg 2020 Dec 19:3134820973395. Epub 2020 Dec 19.

1371Emory University School of Medicine, 71741Grady Memorial Hospital, Atlanta, GA, USA.

Visceral vascular injuries are relatively uncommon even in busy urban trauma centers. The inferior vena cava (IVC) is the most frequently injured visceral vein and can be a complex operative challenge. Despite advances in early volume resuscitation, improved transport times, prompt operative intervention, and hemorrhage control, mortality rates have remained largely unchanged. This article conducts an in-depth review of the literature surrounding IVC injuries and a detailed discussion of operative strategies and management as survivability is ultimately dependent on the grade of injury, location, and the presence of hemorrhagic shock.
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http://dx.doi.org/10.1177/0003134820973395DOI Listing
December 2020

Pulmonary Artery Bullet Embolization: Presentation and Management.

Am Surg 2020 Dec 6:3134820940261. Epub 2020 Dec 6.

1371 Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.

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http://dx.doi.org/10.1177/0003134820940261DOI Listing
December 2020

Is Blush on CT Scan in Patients With Pelvic Fracture Associated With Embolization Rates and Outcomes?

Am Surg 2020 Dec 6:3134820940246. Epub 2020 Dec 6.

1371 Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.

Introduction: In trauma patients with pelvic fractures, computed tomography (CT) scans are a critical tool to evaluate life-threatening hemorrhage. Contrast extravasation, or "blush", on CT may be a sign of bleeding, prompting a consult for angiography and possible embolization. However, the utility of blush on CT is controversial. We sought to evaluate our experience with patients who sustained pelvic fractures and had blush on CT.

Method: A retrospective review was performed for all patients with blunt pelvic fractures between January 1, 2017 and December 31, 2018. Demographic, clinical, radiographic, and injury data were obtained. Comparison of mortality, hospital length of stay (LOS), and intensive care unit (ICU) LOS was performed for 3 subgroups: angio versus no angio; embo versus no embo; prophylactic embo versus therapeutic embo. We also calculated the sensitivity, specify, positive predictive value (PPV), and negative predictive value (NPV) of CT blush to predict the need for embolization.

Results: 889 patients were found to have a blunt pelvic fracture. 51 patients had blush on CT scan. 29 (56.9%) underwent angiography. 17 (58.6%) of these 29 patients were found to have extravasation and were embolized. 12 patients had an angio with no extravasation, and 6 of these patients (50%) underwent prophylactic embolization. No significant difference was found for hospital LOS, ICU LOS, or mortality in our 3 groups. Sensitivity, specificity, PPV, and NPV for CT blush were 74%, 96%, 33%, 99%, respectively.

Conclusion: Patients with active extravasation undergoing embolization had similar outcomes to patients without active extravasation. Blush on CT scan had low sensitivity and low PPV but high specificity and high NPV. Future studies need to include careful attention to the CT protocol utilized as well as patient selection.
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http://dx.doi.org/10.1177/0003134820940246DOI Listing
December 2020

Blunt Traumatic Injury to the Superficial Femoral Artery in a Morbidly Obese Female: Case Report Using Endovascular Covered Stent Repair.

Vasc Endovascular Surg 2021 Feb 10;55(2):192-195. Epub 2020 Sep 10.

Marcus Trauma Center, Emory University School of Medicine, 71741Grady Memorial Hospital, Atlanta, GA, USA.

Lower extremity vascular injuries following trauma are rare events that require prompt identification and management in order to prevent ischemia and limb loss. Endovascular approaches, rather than traditional open procedures, are increasingly used to treat a wide range of vascular disease. The use of endovascular repair for revascularization in the trauma setting is not routine but may provide an appealing alternative in select trauma patients and injuries. We present a case of successful endovascular repair with stent grafting of a superficial femoral artery intimal injury following a femur fracture in a 35-year-old morbidly obese female and review the current literature regarding the use of endovascular therapy in the trauma setting.
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http://dx.doi.org/10.1177/1538574420954576DOI Listing
February 2021

Traumatic Blunt Injuries to the Celiac Artery: A 5-Year Review From a Level I Trauma Center.

Am Surg 2020 Dec 8;86(12):1651-1655. Epub 2020 Jul 8.

1374 Department of Surgery, Morehouse School of Medicine, Atlanta, GA, USA.

Background: Injury to the celiac artery secondary to a blunt mechanism of trauma is an extremely rare injury that accounts for only 1%-2% of all visceral vascular lesions. Although rare, this injury is associated with significant mortality. Despite this high mortality, there are currently only a few published case series of blunt celiac artery injuries in the literature. This study sought to review all cases of blunt celiac artery injuries that presented to our Level I trauma center over a 5-year period.

Methods: This was a retrospective chart review of all patients who presented with a traumatic blunt celiac artery injury between January 2012 and March 2017.

Results: A total of 10 patients met the inclusion criteria for this study. The majority of patients were male (7/10, 70%), the average age was 38.3 ± 16.1 years, and overall mortality was 20% (2/10). On average, patients spent 10.2 ± 6.5 days in the hospital, 4.4 ± 4.5 days in the ICU, and 1.6 ± 2.0 days on the ventilator. The majority of patients presented with either an intimal dissection (3/10, 30%) or an intraluminal thrombus (3/10, 30%). Other injuries included pseudoaneurysms (2/10, 20%), complete avulsion (1/10, 10%), and an intimal dissection with thrombus (1/10, 10%). Of these injuries, 2 (20%) were noted to have retrograde flow on imaging studies including computed tomography angiography and a visceral angiogram. The majority of patients (8/10, 80%) were managed nonoperatively, and 5 (50%) patients were discharged home on aspirin. One patient who was initially managed nonoperatively required an unplanned return to the operating room for ischemic bowel, liver, and stomach. There were no other complications noted.

Discussion: Traumatic blunt injury to the celiac artery is rare. Although there are multiple treatment options, there is currently no consensus in regard to management guidelines. In this case series, the majority of patients were successfully managed nonoperatively suggesting that a selective approach for intervention on patients with a blunt celiac artery injury should be considered.
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http://dx.doi.org/10.1177/0003134820933572DOI Listing
December 2020

Tracheoinnominate Fistula After Percutaneous Tracheostomy: Successful Management with Endovascular Stenting.

Am Surg 2020 Jun 29:3134820923330. Epub 2020 Jun 29.

1371Department of Surgery, Emory University School of Medicine, Grady Memorial Hospital, Atlanta, GA, USA.

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http://dx.doi.org/10.1177/0003134820923330DOI Listing
June 2020

Breast Reconstruction in the Social Media Age.

Aesthet Surg J 2021 01;41(2):200-205

Division of Plastic and Reconstructive Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, GA.

Background: The internet and social media are sources of information regarding breast reconstruction, which can educate and influence patients.

Objectives: This study aimed to evaluate internet and social media usage by breast reconstruction patients and its impact on patients.

Methods: Eighty-six breast reconstruction patients over a 7-month period answered an anonymous survey, which queried demographics, reconstruction type, internet usage, social media usage, expectations, and impact on decisions. Fisher's exact test was performed to evaluate the use of social media.

Results: Overall, 95% of patients used the internet for breast reconstruction information. The information was found to be easy to understand by 70% of patients, helpful by 76%, and trustworthy by 60%. The information influenced decisions regarding procedure by 23% of patients, regarding surgeon by 23%, and regarding hospital by 22%. Social media was used by 71% of the patients; 62% of patients found it easy to understand, 57% found it helpful, and 48% found it trustworthy. The information influenced decisions regarding procedure by 16% of patients, regarding surgeon by 11%, and regarding hospital by 10%. Twenty-six percent of women expected their final breast reconstruction to look better than their premastectomy breasts, 55% as good or similar, and 12% reported appearance to be unimportant. Women found social media information to be less helpful than internet information. There was no significant association between expectations and social media vs no social media usage.

Conclusions: Patients who undergo breast reconstruction use the internet and social media as sources of information. Although the information is generally trusted, it does not seem to heavily influence patient decision-making. Providers remain patients' main source of information, and need to direct patients to high-quality and accessible resources.
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http://dx.doi.org/10.1093/asj/sjaa204DOI Listing
January 2021

The role of diagnostic laparoscopy for trauma at a high-volume level one center.

Surg Endosc 2021 Jun 4;35(6):2667-2670. Epub 2020 Jun 4.

Department of Surgery, Emory University School of Medicine, 525 Glen Iris Dr. NE #2532, Atlanta, GA, 30308, USA.

Background: The role of minimally invasive surgery in trauma has continued to evolve over the past 20 years. Diagnostic laparoscopy (DL) has become increasingly utilized for the diagnosis and management of both blunt and penetrating injuries.

Objective: While the safety and feasibility of laparoscopy has been established for penetrating thoracoabdominal trauma, it remains a controversial tool for other injury patterns due to the concern for complications and missed injuries. We sought to examine the role of laparoscopy for the initial management of traumatic injuries at our urban Level 1 trauma center.

Methods: All trauma patients who underwent DL for blunt or penetrating trauma between 2009 and 2018 were retrospectively reviewed. Demographic data, indications for DL, injuries identified, rate of conversion to open surgery, and outcomes were evaluated.

Results: A total of 316 patients were included in the cohort. The mean age was 34.9 years old (± 13.7), mean GCS 14 (± 3), and median ISS 10 (4-18). A total of 110/316 patients (35%) sustained blunt injury and 206/316 patients (65%) sustained penetrating injury. Indications for DL included evaluation for peritoneal violation (152/316, 48%), free fluid without evidence of solid organ injury (52/316, 16%), evaluation of bowel injury (42/316, 13%), and evaluation for diaphragmatic injury (35/316, 11%). Of all DLs, 178/316 (56%) were negative for injury requiring intervention, which was 58% of blunt cases and 55% of penetrating cases. There were no missed injuries noted. Average hospital length of stay was significantly shorter for patients that underwent DL vs conversion to open exploration (2.2 days vs. 4.5 days, p < 0.05).

Conclusion: In this single institution, retrospective study, the high volume of cases appears to show that DL is a reliable tool for detecting injury and avoiding potential negative or non-therapeutic laparotomies. However, when injuries were present, the high rate of conversion to open exploration suggests that its utility for therapeutic intervention warrants further study.
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http://dx.doi.org/10.1007/s00464-020-07687-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271957PMC
June 2021

Pharmacologic Therapy is Not Associated with Stroke Prevention in Patients with Isolated Blunt Vertebral Artery Injury.

Ann Vasc Surg 2021 Jan 29;70:137-142. Epub 2020 May 29.

Division of Vascular Surgery and Endovascular Therapy, Emory University, Atlanta, GA. Electronic address:

Background: Vertebral artery injury (VAI) is often grouped with carotid artery injury into a broader classification of blunt cerebrovascular injury, despite fundamental differences in mechanism of injury and outcome. This study seeks to evaluate the efficacy of medical therapy in preventing strokes for isolated VAI.

Methods: Patients with isolated blunt VAI (2011-2018) were identified from the trauma registry of a level I trauma center. A retrospective chart review was conducted excluding patients with concomitant carotid artery injury. Factors examined included demographics, injury characteristics, anatomic classification, and management strategy. Patients were stratified by whether they received pharmacological (antiplatelet or anticoagulation) therapy. The primary outcome was new posterior circulation stroke within 30 days of injury as confirmed by imaging studies.

Results: A total of 206 patients with blunt VAI were included. Median Injury Severity Score was 17 and 33 (16.0%) patients presented with Glasgow Coma Scale <8. The most common mechanism of injury was motor vehicle collision (58.7%). The injuries were bilateral in 38 (18.5%) patients and 73 (35.4%) suffered multisegmental injuries. The anatomic severity of injuries was Grade 1 = 38.8%, Grade 2 = 25.7%, Grade 3 = 4.9%, Grade 4 = 30.6%, and Grade 5 = 0.5%. There was no correlation between anatomic grade and stroke (P = 0.11) or initiation of pharmacologic therapy (P = 0.30). In total, 172 (84%) patients received pharmacological therapy with no differences in baseline characteristics between treated and untreated patients. Overall, the 30-day stroke rate was 1.9%. There was no difference in stroke rate between patients who received medical therapy versus those who did not (5.9% vs. 1.2%, P = 0.13). In subgroup analysis by injury severity, medical therapy did not improve stroke rates. Among patients treated with aspirin, there was no difference in stroke rate between doses of 81 vs. 325 mg (1.1% vs. 0%, P = 1).

Conclusions: Isolated VAI is associated with a very low risk of stroke and treatment with medical therapies including antiplatelet or anticoagulation does not improve risk of stroke.
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http://dx.doi.org/10.1016/j.avsg.2020.05.029DOI Listing
January 2021

Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGFβ signalling.

Cardiovasc Res 2021 01;117(1):201-211

Department of Biology, San Diego State University, North Life Sciences, 426, 5500 Campanile Drive, San Diego, CA 92182, USA.

Aims: Telomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and up-regulation of proapoptotic transcription factors. Pim1 is a cardioprotective kinase that antagonizes the aging phenotype of cardiomyocytes and delays cellular senescence by maintaining telomere length, but the mechanism remains unknown. Another pathway responsible for regulating telomere length is the transforming growth factor beta (TGFβ) signalling pathway where inhibiting TGFβ signalling maintains telomere length. The relationship between Pim1 and TGFβ has not been explored. This study delineates the mechanism of telomere length regulation by the interplay between Pim1 and components of TGFβ signalling pathways in proliferating A549 cells and post-mitotic cardiomyocytes.

Methods And Results: Telomere length was maintained by lentiviral-mediated overexpression of PIM1 and inhibition of TGFβ signalling in A549 cells. Telomere length maintenance was further demonstrated in isolated cardiomyocytes from mice with cardiac-specific overexpression of PIM1 and by pharmacological inhibition of TGFβ signalling. Mechanistically, Pim1 inhibited phosphorylation of Smad2, preventing its translocation into the nucleus and repressing expression of TGFβ pathway genes.

Conclusion: Pim1 maintains telomere lengths in cardiomyocytes by inhibiting phosphorylation of the TGFβ pathway downstream effectors Smad2 and Smad3, which prevents repression of telomerase reverse transcriptase. Findings from this study demonstrate a novel mechanism of telomere length maintenance and provide a potential target for preserving cardiac function.
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http://dx.doi.org/10.1093/cvr/cvaa066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797214PMC
January 2021

Physiological and evolutionary implications of tetrameric photosystem I in cyanobacteria.

Nat Plants 2019 12 9;5(12):1309-1319. Epub 2019 Dec 9.

Biochemistry and Cellular and Molecular Biology Department, University of Tennessee, Knoxville, TN, USA.

Photosystem I (PSI) is present as trimeric complexes in most characterized cyanobacteria and as monomers in plants and algae. Recent reports of tetrameric PSI have raised questions regarding its structural basis, physiological role, phylogenetic distribution and evolutionary significance. Here, we examined PSI in 61 cyanobacteria, showing that tetrameric PSI, which correlates with the psaL gene and a distinct genomic structure, is widespread among heterocyst-forming cyanobacteria and their close relatives. Physiological studies revealed that expression of tetrameric PSI is favoured under high light, with an increased content of novel PSI-bound carotenoids (myxoxanthophyll, canthaxanthan and echinenone). In sum, this work suggests that tetrameric PSI is an adaptation to high light intensity, and that change in PsaL leads to monomerization of trimeric PSI, supporting the hypothesis of tetrameric PSI being the evolutionary intermediate in the transition from cyanobacterial trimeric PSI to monomeric PSI in plants and algae.
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http://dx.doi.org/10.1038/s41477-019-0566-xDOI Listing
December 2019

Atoms to Phenotypes: Molecular Design Principles of Cellular Energy Metabolism.

Cell 2019 11;179(5):1098-1111.e23

Department of Physics, NSF Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

We report a 100-million atom-scale model of an entire cell organelle, a photosynthetic chromatophore vesicle from a purple bacterium, that reveals the cascade of energy conversion steps culminating in the generation of ATP from sunlight. Molecular dynamics simulations of this vesicle elucidate how the integral membrane complexes influence local curvature to tune photoexcitation of pigments. Brownian dynamics of small molecules within the chromatophore probe the mechanisms of directional charge transport under various pH and salinity conditions. Reproducing phenotypic properties from atomistic details, a kinetic model evinces that low-light adaptations of the bacterium emerge as a spontaneous outcome of optimizing the balance between the chromatophore's structural integrity and robust energy conversion. Parallels are drawn with the more universal mitochondrial bioenergetic machinery, from whence molecular-scale insights into the mechanism of cellular aging are inferred. Together, our integrative method and spectroscopic experiments pave the way to first-principles modeling of whole living cells.
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http://dx.doi.org/10.1016/j.cell.2019.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075482PMC
November 2019

The American Association for the Surgery of Trauma Organ Injury Scale 2018 update for computed tomography-based grading of renal trauma: a primer for the emergency radiologist.

Emerg Radiol 2020 Feb 5;27(1):63-73. Epub 2019 Sep 5.

Division of Emergency Radiology, Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, 30308, USA.

The most widely used trauma injury grading system is the Organ Injury Scale (OIS) by the American Association for the Surgery of Trauma (AAST). The AAST OIS for renal trauma was revised in 2018 to reflect necessary updates based on decades of experience with computed tomography (CT)-based injury diagnosis and, specifically, to better incorporate vascular injuries, which were not comprehensively addressed in the original OIS. In this review article, we describe CT findings of the AAST OIS for the kidney according to the 2018 revision, with an emphasis on real-world application, and highlight important differences from the prior grading scheme. Routine use of this grading system allows for a standardized classification of the range of renal injuries to aid in management, adding value in the imaging care of trauma patients.
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http://dx.doi.org/10.1007/s10140-019-01721-zDOI Listing
February 2020

Expeditious Diagnosis and Laparotomy for Patients with Acute Abdominal Compartment Syndrome May Improve Survival.

Am Surg 2018 Nov;84(11):1836-1840

Causes of abdominal compartment syndrome (ACS) are varied and can result from both medical and surgical diseases. Early recognition of ACS and prompt surgical treatment has been shown to improve mortality. We hypothesize that earlier recognition of ACS and earlier involvement by surgical specialists may improve mortality. A retrospective review between July 2010 and July 2015 was performed of adult patients who underwent decompressive laparotomy for ACS. Patients were divided into surgical and medical intensive care units (SICU and MICU) arms. Twenty patients were included (MICU = 12; SICU = 8) without significant difference between the groups. Median time from admission to suspicion for MICU patients was 60 hours 13 hours for SICU patients ( = 0.013). Time from suspicion to surgical consult was 60 minutes 0 minutes, respectively ( = 0.003), however, time from surgical consult to intervention was not different. Mortality rate in the MICU was 83 per cent 12.5 per cent in the SICU ( = 0.005). Patients in the SICU who developed ACS were more quickly diagnosed than those in the MICU. These patients had a shorter time from suspicion of ACS to surgical consultation and eventual surgical intervention, and was associated with improved survival. A multidisciplinary approach, including early surgical consultation, for patients in whom there is a suspicion of ACS may contribute to improved mortality.
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November 2018

Long-term results of multicatheter interstitial high-dose-rate brachytherapy for accelerated partial-breast irradiation.

Brachytherapy 2019 Mar - Apr;18(2):211-216. Epub 2018 Dec 13.

Département de radio-oncologie, Centre Intégré de Santé et de Services Sociaux de l'Outaouais, Gatineau, Quebec, Canada.

Purpose: The purpose of this study was to report the long-term results of women treated in one center with accelerated partial-breast irradiation (APBI) with interstitial high-dose-rate (HDR) brachytherapy.

Materials And Methods: We analyzed data from women treated in one center with adjuvant interstitial HDR brachytherapy for early-stage breast cancer. Treatment regimen was homogeneous for all women with treatment dose 32Gy in 8 fractions twice daily given to the tumor bed with interstitial HDR brachytherapy.

Results: About 364 women were treated with interstitial HDR brachytherapy as APBI from March 2000 to March 2014. Mean age at diagnosis was 62 years. Stage distribution was as follows: T1a = 12%, T1b = 33%, T1c = 40%, T2 = 14%, and Tis = 1%. 97% of patients were N0. 88% had invasive ductal carcinoma. 86% had positive hormone receptor status. 14 ipsilateral breast tumor recurrences were identified with 12 deemed local recurrences and 2 deemed to be second ipsilateral primaries. Actuarial 5-year and 10-year overall survival rates were 95.1% and 92.2%, respectively. Actuarial 5-year and 10-year local relapse-free survival rates were 96.2% and 88.8%, respectively.

Conclusions: The results of this previously unreported series of women treated with a homogeneous APBI method exclusively with interstitial HDR brachytherapy present further data justifying that in appropriately selected women, APBI with interstitial brachytherapy provides rates of local control and survival comparable with whole-breast irradiation.
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http://dx.doi.org/10.1016/j.brachy.2018.11.004DOI Listing
July 2019

Cecal volvulus with gangrene following Mitrofanoff procedure.

Urol Case Rep 2018 Nov 11;21:21-23. Epub 2018 Aug 11.

Department of Surgery, Morehouse School of Medicine, Atlanta, GA, USA.

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http://dx.doi.org/10.1016/j.eucr.2018.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104579PMC
November 2018

"Black Esophagus" and Gastric Volvulus Following Slipped Laparoscopic Adjustable Gastric Band.

Obes Surg 2018 09;28(9):2941-2948

Department of Surgery, Morehouse School of Medicine, 720 Westview Dr, SW, Atlanta, GA, 30310, USA.

To review the entity "black esophagus" and sequela of a slipped laparoscopic adjustable band. The patient's history, physical examination, imaging, and endoscopic findings were reviewed. Detailed review of pathophysiology, presentation, diagnosis, management, and natural history was conducted. "Black esophagus," also known as acute esophageal necrosis (AEN), is a rare condition resulting in black discoloration of the mid to distal esophagus with less than a hundred reported cases. It has not been previously documented in bariatric surgery or following laparoscopic adjustable gastric banding. The volvulus was reduced at surgery, and the esophageal changes resolved without sequela. "Black esophagus" is an acute, ominous-appearing condition with a spectrum ranging from superficial mucosal disease to transmural involvement with perforation. Fortunately, esophageal resection is rarely required.
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http://dx.doi.org/10.1007/s11695-018-3354-1DOI Listing
September 2018

Successful treatment of massive hemothorax with class IV shock using aortography with transcatheter embolization of actively bleeding posterior left intercostal arteries after penetrating left chest trauma: A case for the hybrid OR.

Int J Surg Case Rep 2018 3;48:109-112. Epub 2018 May 3.

Morehouse School of Medicine, Atlanta, GA, USA. Electronic address:

Hemothorax is a common occurrence after blunt or penetrating injury to the chest. Posterior intercostal vessel hemorrhage as a cause of major intrathoracic bleeding is an infrequent source of massive bleeding. Selective angiography with trans-catheter embolization may provide a minimally invasive and efficient method of controlling bleeding refractory to surgical treatment.

Presentation Of Case: A 19 year-old male sustained a gunshot wound to his left chest with massive hemothorax and refractory hemorrhage. He was emergently taken to the operating room for thoracotomy and was found to have uncontrollable bleeding from the chest due to left posterior intercostal artery transection. The bleeding persisted despite multiple attempts with sutures, clips and various hemostatic agents. Thoracic aortography was undertaken and revealed active bleeding from the left 7th posterior intercostal artery, which was coil-embolized. The patient's hemodynamic status significantly improved and he was transferred to the intensive care unit.

Discussion: Posterior intercostal bleeding is a rare cause of massive hemothorax. Bleeding from these arteries may be difficult to control due to limited exposure in that area. Transcatheter-based arterial embolization is a reliable and feasible option for arresting hemorrhage following failed attempts at hemorrhage control from thoracotomy.

Conclusion: Massive hemothorax from intercostal arterial bleeding is a rare complication after penetrating chest injury (Aoki et al., 2003). Selective, catheter-based embolization is a useful therapeutic option for hemorrhage control and can be expeditiously employed if a hybrid operating room is available.
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http://dx.doi.org/10.1016/j.ijscr.2018.04.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041426PMC
May 2018

Variations in institutional review board processes and consent requirements for trauma research: an EAST multicenter survey.

Trauma Surg Acute Care Open 2018 30;3(1):e000176. Epub 2018 May 30.

Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Oversight of human subject research has evolved considerably since its inception. However, previous studies identified a lack of consistency of institutional review board (IRB) determination for the type of review required and whether informed consent is necessary, especially for prospective observational studies, which pose minimal risk of harm. We hypothesized that there is significant inter-institution variation in IRB requirements for the type of review and necessity of informed consent, especially for prospective observational trials without blood/tissue utilization. We also sought to describe investigators' and IRB members' attitudes toward the type of review and need for consent. Eastern Association for the Surgery of Trauma (EAST) and IRB members were sent an electronic survey on IRB review and informed consent requirement. We performed descriptive analyses as well as Fisher's exact test to determine differences between EAST and IRB members' responses. The response rate for EAST members from 113 institutions was 13.5%, whereas a convenience sample of IRB members from 14 institutions had a response rate of 64.4%. Requirement for full IRB review for retrospective studies using patient identifiers was reported by zero IRB member compared with 13.1% of EAST members (p=0.05). Regarding prospective observational trials without blood/tissue collection, 48.1% of EAST members reported their institutions required a full IRB review compared with 9.5% of IRB members (p=0.01). For prospective observational trials with blood/tissue collection, 80% of EAST members indicated requirement to submit a full IRB review compared with only 13.6% of IRB members (p<0.001). Most EAST members (78.6%) stated that informed consent is not ethically necessary in prospective observational trials without blood/tissue collection, whereas most IRB members thought that informed consent was ethically necessary (63.6%, p<0.001). There is significant variation in perception and practice regarding the level of review for prospective observational studies and whether informed consent is necessary. We recommend future interdisciplinary efforts between researchers and IRBs should occur to better standardize local IRB efforts.

Level Of Evidence: IV.
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http://dx.doi.org/10.1136/tsaco-2018-000176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976138PMC
May 2018