Publications by authors named "Hang Lee"

614 Publications

Immune checkpoint inhibitors for cancer and venous thromboembolic events.

Eur J Cancer 2021 Oct 15;158:99-110. Epub 2021 Oct 15.

Cardiovascular Imaging Research Center, Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Background: Immune checkpoint inhibitors (ICIs) are widely used cancer treatments. There are limited data on the risk for developing venous thromboembolism (VTE) among patients on an ICI.

Methods: This was a retrospective study of 2854 patients who received ICIs at a single academic centre. VTE events, defined as a composite of deep vein thrombosis or pulmonary embolism, were identified by individual chart review and blindly adjudicated using standard imaging criteria. A self-controlled risk-interval design was applied with an 'at-risk period' defined as the two-year period after and the 'control period', defined as the two-year before treatment. The hazard ratio (HR) was calculated using a fixed-effect proportional hazards model.

Results: Of the 2854 patients, 1640 (57.5%) were men; the mean age was 64 ± 13 years. The risk for VTE was 7.4% at 6 months and 13.8% at 1 year after starting an ICI. The rate of VTE was > 4-fold higher after starting an ICI (HR 4.98, 95% CI 3.65-8.59, p < 0.001). There was a 5.7-fold higher risk for deep vein thrombosis (HR 5.70, 95% CI 3.79-8.59, p < 0.001) and a 4.75-fold higher risk for pulmonary embolism (HR 4.75, 95% CI 3.20-7.10, p < 0.001). Comparing patients with and without a VTE event, a history of melanoma and older age predicted lower risk of VTE, while a higher Khorana risk score, history of hypertension and history of VTE predicted higher risk.

Conclusions: The rate of VTE among patients on an ICI is high and increases after starting an ICI.
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http://dx.doi.org/10.1016/j.ejca.2021.09.010DOI Listing
October 2021

Gender differences in dermatologist practice locations in the United States: A cross-sectional analysis of current gender gaps.

Int J Womens Dermatol 2021 Sep 3;7(4):435-440. Epub 2021 May 3.

Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts.

Background: The percentage of female dermatologists has increased from 6.9% in 1970 to 48.9% in 2017. Despite the changing gender composition of the dermatologist workforce, it is unknown whether there are gender-based differences in dermatology practice locations.

Objective: This study aimed to characterize gender-based differences in dermatology practice locations across the United States.

Methods: A cross-sectional study of all dermatologists in the 2020 Centers for Medicare and Medicaid Services Physician Compare Database was performed. The number of self-identified female dermatologists and total dermatologists in each county and state was tabulated, and Spearman's correlation coefficients between county-level demographic and socioeconomic characteristics and female practices were calculated.

Results: Among 11,911 dermatologists, 5945 (49.9%) self-identified as female and 5966 (50.1%) as male. Of the 1052 counties with a dermatologist, 291 (27.7%) had no female dermatologist and 149 (14.2%) had no male dermatologist. The percentage of female dermatologists in each state ranged from 18.4% to 62.2%. Female dermatologists practiced more in areas with a higher percentage of democratic voters ( = +0.22) and higher median household income ( = +0.18), and less in rural counties ( = -0.18) or counties with higher uninsured rates (r = -0.11).

Conclusion: Female dermatologists remain significantly underrepresented in some regions in the United States, particularly in the Mountain states and rural counties. As women continue entering the dermatologist workforce, these results can inform workforce planning strategies to improve the distribution and accessibility of dermatologists across the United States.
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http://dx.doi.org/10.1016/j.ijwd.2021.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484981PMC
September 2021

Age and Phenotype of Patients With Plaque Erosion.

J Am Heart Assoc 2021 Oct 25;10(19):e020691. Epub 2021 Sep 25.

Cardiology Division Massachusetts General HospitalHarvard Medical School Boston MA.

Background A recent study reported that the outcome of patients with plaque erosion treated with stenting is poor when the underlying plaque is lipid rich. However, the detailed phenotype of patients with plaque erosion, particularly as related to different age groups, has not been systematically studied. Methods and Results Patients with acute coronary syndromes caused by plaque erosion were selected from 2 data sets. Demographic, clinical, angiographic, and optical coherence tomography findings of the culprit lesion were compared between 5 age groups. Among 579 erosion patients, male sex and current smoking were less frequent, and hypertension, diabetes, and chronic kidney disease were more frequent in older patients. ST-segment-elevation myocardial infarction was more frequent in younger patients. Percentage of diameter stenosis on angiogram was greater in older patients. The prevalence of lipid-rich plaque (27.3% in age <45 years and 49.4% in age ≥75 years, <0.001), cholesterol crystal (3.9% in age <45 years and 21.8% in age ≥75 years, =0.027), and calcification (5.5% in age <45 years and 54.0% in age ≥75 years, <0.001) increased with age. After adjusting risk factors, younger patients were associated with the presence of thrombus, and older patients were associated with greater percentage of diameter stenosis and the presence of lipid-rich plaque and calcification. Conclusions The demographic, clinical, angiographic, and plaque phenotypes of patients with plaque erosion distinctly vary depending on age. This may affect the clinical outcome in these patients. Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT03479723, NCT02041650.
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http://dx.doi.org/10.1161/JAHA.120.020691DOI Listing
October 2021

SAFE APPROACH FOR FLEXOR DIGITORUM PROFUNDUS I AND II USING THE PALMARIS LONGUS TENDON.

Arch Phys Med Rehabil 2021 Sep 10. Epub 2021 Sep 10.

Department of Physical Medicine and Rehabilitation, Korea University Ansan Hospital, Gyeonggi-do, Korea. Electronic address:

Objective: To investigate a safe and accurate approach to achieve needle insertion for electromyography of the flexor digitorum profundus (FDP) I and II muscles by identifying the anatomical relationship between the palmaris longus (PL) tendon, FDP muscle, and neurovascular bundle using ultrasonography.

Design: Descriptive study SETTING: Department of Physical Medicine and Rehabilitation PARTICIPANTS: Healthy individuals (age, 20-70 years) without any diseases (N=29; 15 men, 14 women; 58 forearms).

Interventions: Ultrasonography MAIN OUTCOME MEASURES: The FDP I and II muscles were transversely scanned on the volar aspect of the forearm at the junction of the middle and distal third between the medial epicondyle and ulnar styloid process. The distances and angles from the medial border of the PL tendon to FDP I, II, and median nerve were measured.

Results: The probability of damage to the neurovascular structures and the accuracy of entering the FDP I and II muscles were calculated for three imaginary needle insertion angles (61.7°, 100.6°, and 90°). When the needle was inserted at an angle of 61.7°, it reached FDP I with an accuracy of 91.4%. Upon needle insertions at 90° and 100.6°, the needle reached FDP II with accuracies of 90% and 89.6%, respectively. In all three cases (61.7°, 90°, and 100.6°), there was no chance of penetrating the blood vessels or nerves.

Conclusion: EMG of FDP I and II can be performed precisely and safely with the anterior approach at the distal one-third between the medial epicondyle and ulnar styloid process using the PL tendon.
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http://dx.doi.org/10.1016/j.apmr.2021.08.011DOI Listing
September 2021

Coronary plaque and clinical characteristics of South Asian (Indian) patients with acute coronary syndromes: An optical coherence tomography study.

Int J Cardiol 2021 Nov 3;343:171-179. Epub 2021 Sep 3.

Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Division of Cardiology, Kyung Hee University Hospital, Seoul, Republic of Korea. Electronic address:

Background: South Asians, and Indians in particular, are known to have a higher incidence of premature atherosclerosis and acute coronary syndromes (ACS) with worse clinical outcomes, compared to populations with different ethnic backgrounds. However, the underlying pathobiology accounting for these differences has not been fully elucidated.

Methods: ACS patients who had culprit lesion optical coherence tomography (OCT) imaging were enrolled. Culprit plaque characteristics were evaluated using OCT.

Results: Among 1315 patients, 100 were South Asian, 1009 were East Asian, and 206 were White. South Asian patients were younger (South Asians vs. East Asians vs. Whites: 51.6 ± 13.4 vs. 65.4 ± 11.9 vs. 62.7 ± 11.7; p < 0.001) and more frequently presented with ST-segment elevation myocardial infarction (STEMI) (77.0% vs. 56.4% vs. 35.4%; p < 0.001). On OCT analysis after propensity group matching, plaque erosion was more frequent (57.0% vs. 38.0% vs. 50.0%; p = 0.003), the lipid index was significantly greater (2281.6 [1570.8-3160.6] vs. 1624.3 [940.9-2352.4] vs. 1303.8 [1090.0-1757.7]; p < 0.001), and the prevalence of layered plaque was significantly higher in the South Asian group than in the other two groups (52.0% vs. 30.0% vs. 34.0%; p = 0.003).

Conclusions: Compared to East Asians and Whites, South Asians with ACS were younger and more frequently presented with STEMI. Plaque erosion was the predominant pathology for ACS in South Asians and their culprit lesions had more features of plaque vulnerability.

Clinical Trial Registration: http://www.clinicaltrials.gov, NCT03479723.
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http://dx.doi.org/10.1016/j.ijcard.2021.08.048DOI Listing
November 2021

Correction to: Low insertion of cystic duct increases risk for common bile duct stone recurrence.

Surg Endosc 2021 Jul 22. Epub 2021 Jul 22.

Department of Internal Medicine, Hanyang University College of Medicine, 222-1 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

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http://dx.doi.org/10.1007/s00464-021-08623-7DOI Listing
July 2021

Potent platelet inhibition with peri-procedural tirofiban may attenuate progression of atherosclerosis in patients with acute coronary syndromes.

J Thromb Thrombolysis 2021 Jul 17. Epub 2021 Jul 17.

Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRB 800, Boston, MA, 02114, USA.

Organization of platelet-rich thrombus at the site of plaque disruption may contribute to rapid progression of atherosclerosis. This study was conducted to investigate if potent platelet inhibition therapy in patients with acute coronary syndromes (ACS) mitigates plaque progression. Patients enrolled in the EROSION study who presented with ACS caused by plaque erosion and underwent serial imaging of the culprit lesion by optical coherence tomography at baseline, 1 month, and 1 year were included. Among 49 patients, 32 (65.3%) patients were treated with glycoprotein IIb/IIIa inhibitor (GPI) in addition to aspirin and ticagrelor. The increase in area stenosis from baseline to 1-year follow-up was significantly smaller in patients treated with GPI, compared to those without GPI therapy (4.8% [- 1.6 to 10.9] vs. 9.6% [4.0 to 21.3], p = 0.031). The cohort was divided into 2 groups based on culprit lesion phenotype at 1 year: Group A, new layer formation at 1-year that was not present at baseline (n = 18); Group B, no new layer formation (n = 31). A new layer was less frequently found at 1 year in patients treated with GPI than in those without GPI (25.0% vs. 58.8%, p = 0.019). Group A, compared to Group B, was associated with a greater increase in area stenosis (19.0 ± 16.4% vs. 3.7 ± 7.1%; p < 0.001). Potent platelet inhibition with GPI in patients with ACS caused by plaque erosion was associated with lower incidence of new layer formation and less plaque progression.
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http://dx.doi.org/10.1007/s11239-021-02500-9DOI Listing
July 2021

Sequential Phase II clinical trials evaluating CRLX101 as monotherapy and in combination with bevacizumab in recurrent ovarian cancer.

Gynecol Oncol 2021 Sep 7;162(3):661-666. Epub 2021 Jul 7.

Massachussetts General Hospital, Boston, MA, United States of America. Electronic address:

Background: Topoisomerase-1 inhibitors are an important class of cytotoxics associated with toxicity that limits their use. CRLX101 is a novel cyclodextrin-containing polymer conjugate of camptothecin (CPT) that self-assembles into nanoparticles to deliver sustained levels of active CPT into cancer cells while substantially reducing systemic exposure.

Methods: We conducted sequential phase II, open label, single arm clinical trials to evaluate CRLX101 as a single agent (n = 29) and with bevacizumab (Bev) (n = 34). Patients (pts) had measurable recurrent epithelial ovarian, tubal or primary peritoneal cancer, that could be platinum refractory, resistant or sensitive. Cohort A (Single agent CRLX101) allowed up to 3 prior chemotherapy regimens, but no prior topo-1 inhibitors. Pts received CRLX101 15 mg/m IV every 14 days Q28 with response evaluation every 2 cycles. Cohort B also received Bev 10 mg/kg D1,15 Q28, and included only platinum resistant disease with up to 2 prior lines, and more rigorous eligibility criteria.

Results: CRLX101 was well tolerated other than nausea, fatigue and anemia. 29 pts. received a median of 3 (1-16) cycles with a clinical benefit rate (CBR) of 68% and overall response rate (ORR) of 11%. With the addition of Bev in Cohort B (n = 34), the CBR was increased to 95% and the ORR to 18%. PFS was 4.5 months (0.9 to 15.9 months) in Cohort A and 6.5 months (2.8 to 14.4 months) in Cohort B. Bev increased the incidence of hypertension and qualitatively increased bladder toxicities, but without SAEs.

Conclusions: CRLX101 meets the clinical need for an effective and tolerable topoisomerase I inhibitor and can be safely combined with bevacizumab.
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http://dx.doi.org/10.1016/j.ygyno.2021.07.002DOI Listing
September 2021

Whole genome survey of big cats (Genus: Panthera) identifies novel microsatellites of utility in conservation genetic study.

Sci Rep 2021 07 8;11(1):14164. Epub 2021 Jul 8.

Conservation Genome Resource Bank for Korean Wildlife (CGRB), Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.

Big cats (Genus: Panthera) are among the most threatened mammal groups of the world, owing to hunting, habitat loss, and illegal transnational trade. Conservation genetic studies and effective curbs on poaching are important for the conservation of these charismatic apex predators. A limited number of microsatellite markers exists for Panthera species and researchers often cross-amplify domestic cat microsatellites to study these species. We conducted data mining of seven Panthera genome sequences to discover microsatellites for conservation genetic studies of four threatened big cat species. A total of 32 polymorphic microsatellite loci were identified in silico and tested with 152 big cats, and were found polymorphic in most of the tested species. We propose a set of 12 novel microsatellite markers for use in conservation genetics and wildlife forensic investigations of big cat species. Cumulatively, these markers have a high discriminatory power of one in a million for unrelated individuals and one in a thousand for siblings. Similar PCR conditions of these markers increase the prospects of achieving efficient multiplex PCR assays. This study is a pioneering attempt to synthesise genome wide microsatellite markers for big cats.
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http://dx.doi.org/10.1038/s41598-021-92781-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266911PMC
July 2021

Behavioral and cardiac responses in mature horses exposed to a novel object.

J Anim Sci Technol 2021 May 31;63(3):651-661. Epub 2021 May 31.

Department of Equine Science, Cheju Halla University, Jeju 63092, Korea.

This study aimed to investigate whether breed, sex, and age affected temperament differently (more or less neophobic) in mature horses during a novel object test. The study included Jeju crossbred (n = 12, age = 9.42 ± 4.57 y), Thoroughbred (n = 15, age = 10.73 ± 3.09 y), and Warmblood horses (n = 12, age = 13.08 ± 3.55 y) with the females (n = 22, age = 11.36 ± 4.24 y) and geldings (n = 17, age = 10.65 ± 3.66 y). Jeju crossbreds (Jeju horse × Thoroughbred) are valuable considering their popular usage in Korea, but limited studies have explored temperament of Jeju crossbred horses. A trained experimenter touched the left side of the neck with a white plastic bag (novel object). The test ended when the horse stopped escape response and heart rate (HR) dropped to baseline. Behavioral score and escape duration were measured as behavioral variables. Multiple variables related to HR and heart rate variability (HRV) were measured to reflect emotional state. These included basal HR (BHR), maximum HR (MHR), delay to reach maximum heart rate (Time to MHR), standard deviation of beat-to-beat intervals (SDNN), root mean square of successive differences (RMSSD), and ratio of low to high frequency components of a continuous series of heartbeats (LF/HF). Statistics revealed that Thoroughbreds had significantly higher behavioral scores, and lower RMSSD than Jeju crossbreds ( < 0.05), suggesting greater excitement and fear to the novel object in Thoroughbreds. None of the behavioral or cardiac parameters exhibited sex differences ( < 0.05). Age was negatively correlated with SDNN and RMSSD ( < 0.05), indicating that older horses felt more anxiety to the novelty than younger horses. Thoroughbreds and females had distinct correlations between behavioral and HRV variables in comparison with other groups ( < 0.05), implying that escape duration might be a good indicator of stress, especially in these two groups. These results are expected to improve equine welfare, safety and utility, by providing insights into the temperament of particular horse groups, to better match reactivity levels with specific functions.
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http://dx.doi.org/10.5187/jast.2021.e51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203992PMC
May 2021

Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized, Double-Blinded, Placebo-Controlled Pilot Trial.

Nutrients 2021 May 5;13(5). Epub 2021 May 5.

Department of Epidemiology, Indiana University, Richard M. Fairbanks School of Public Health, Indianapolis, IN 46202, USA.

Autism spectrum disorder (ASD) is a rapidly growing neurodevelopmental disorder. Both probiotics and oxytocin were reported to have therapeutic potential; however, the combination therapy has not yet been studied. We conducted a randomized, double-blinded, placebo-controlled, 2-stage pilot trial in 35 individuals with ASD aged 3-20 years (median = 10.30 years). Subjects were randomly assigned to receive daily PS128 probiotic (6 × 10 CFUs) or a placebo for 28 weeks; starting on week 16, both groups received oxytocin. The primary outcomes measure socio-behavioral severity using the Social Responsiveness Scale (SRS) and Aberrant Behavior Checklist (ABC). The secondary outcomes include measures of the Clinical Global Impression (CGI) scale, fecal microbiome, blood serum inflammatory markers, and oxytocin. All outcomes were compared between the two groups at baseline, 16 weeks, and 28 weeks into treatment. We observed improvements in ABC and SRS scores and significant improvements in CGI-improvement between those receiving probiotics and oxytocin combination therapy compared to those receiving placebo ( < 0.05). A significant number of favorable gut microbiome network hubs were also identified after combination therapy ( < 0.05). The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group. Our findings suggest synergic effects between probiotics PS128 and oxytocin in ASD patients, although further investigation is warranted.
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http://dx.doi.org/10.3390/nu13051552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147925PMC
May 2021

Low insertion of cystic duct increases risk for common bile duct stone recurrence.

Surg Endosc 2021 May 24. Epub 2021 May 24.

Department of Internal Medicine, Hanyang University College of Medicine, 222-1 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

Background: Common bile duct (CBD) stone is one of the most frequent biliary diseases. Recurrence after the complete removal of CBD stones is high, and we aim to evaluate the rate and risk factors for symptomatic recurrence of CBD stones after endoscopic retrograde cholangiopancreatography (ERCP).

Methods: We, retrospectively, reviewed the database of patients who underwent ERCP for CBD stones and subsequent cholecystectomy between January 2015 and December 2017 at a tertiary hospital. The recurrence of symptomatic CBD stones was defined as the presence of a CBD stone with related symptoms at least 6 months after the ERCP procedure. The primary outcomes were recurrence of symptomatic CBD stones and its risk factors.

Results: Among the 362 enrolled patients, 60 experienced a symptomatic recurrence of CBD stones between 6 months and 5 years after the procedure. The mean duration of follow-up was 32.3 ± 8.1 months. The patients with recurrences were older and had a longer follow-up duration. Low insertion of the cystic duct (HR = 2.893, p = 0.016), distal CBD angulation (HR = 1.015, p = 0.034), maximum CBD diameter (HR = 1.070, p = 0.012), number of ERCP sessions at first admission (HR = 1.558, p = 0.032), and cannulation time (HR = 1.030, p = 0.008) were the independent risk factors for symptomatic recurrent CBD stones.

Conclusions: Patients with risk factors, especially those with low cystic duct insertion, are more prone to symptomatic recurrent CBD stones and should be followed more carefully.
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http://dx.doi.org/10.1007/s00464-021-08563-2DOI Listing
May 2021

Comparing machine learning algorithms for predicting ICU admission and mortality in COVID-19.

NPJ Digit Med 2021 May 21;4(1):87. Epub 2021 May 21.

Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

As predicting the trajectory of COVID-19 is challenging, machine learning models could assist physicians in identifying high-risk individuals. This study compares the performance of 18 machine learning algorithms for predicting ICU admission and mortality among COVID-19 patients. Using COVID-19 patient data from the Mass General Brigham (MGB) Healthcare database, we developed and internally validated models using patients presenting to the Emergency Department (ED) between March-April 2020 (n = 3597) and further validated them using temporally distinct individuals who presented to the ED between May-August 2020 (n = 1711). We show that ensemble-based models perform better than other model types at predicting both 5-day ICU admission and 28-day mortality from COVID-19. CRP, LDH, and O saturation were important for ICU admission models whereas eGFR <60 ml/min/1.73 m, and neutrophil and lymphocyte percentages were the most important variables for predicting mortality. Implementing such models could help in clinical decision-making for future infectious disease outbreaks including COVID-19.
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http://dx.doi.org/10.1038/s41746-021-00456-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140139PMC
May 2021

Can Helicobacter pylori eradication affect long-term mortality?

Authors:
Hang Lak Lee

Korean J Intern Med 2021 05 30;36(3):539-540. Epub 2021 Apr 30.

Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea.

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http://dx.doi.org/10.3904/kjim.2021.190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137411PMC
May 2021

Prevalence and clinical characteristics of antibiotics associated drug induced liver injury.

Ann Transl Med 2021 Apr;9(8):642

Department of Internal Medicine, Hanyang University School of Medicine, Seoul, South Korea.

Background: The use of antibiotics increases recently. Accordingly, the incidence of antibiotics associated with drug induced liver injury (DILI) also increases. The purpose of this study is to evaluate the proportion and the clinical characteristics of antibiotic associated with DILI.

Methods: This study is a retrospective study of analyzed adult patients who were referred to the department of hepatology for the elevation of liver function tests and the frequency of elevated liver enzyme of patients with prescribed antibiotics during the same period at outpatient setting as a validation set.

Results: Antibiotics associated with DILI (64.0%) are the most common reason agent among consulting to hepatology department. Rheumatoid arthritis related drugs (11.0%), health supplements (5.0%), herbal medicines (4.0%), anti-viral drugs, anti-inflammatory analgesics/acetaminophen and lipid-lowering agents (3.0%) were next common causative drug for DILI in inpatients setting (training set). The frequency of antibiotics associated with DILI was high in order of flomoxef, cetrazole, ceftriaxone, vancomycin, piperacillin/tazobactam and amoxicillin/clavulanate. In the same period, 32% of the patients who prescribed flomoxef showed elevated liver enzyme levels above the upper normal limit. The prevalence of flomoxef induced DILI (>3 folds of ALT) was 13% and liver enzyme levels were five times higher than upper normal limits in 5% of flomoxef groups. Hypertension or diabetes was the risk factor of flomoxef associated with DILI.

Conclusions: The Prevalence of antibiotics associated with DILI was 2-14%. Co-morbidity with diabetes and hypertension was the risk factor of flomoxef associated with DILI.
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http://dx.doi.org/10.21037/atm-20-5144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106034PMC
April 2021

The dynamics of human bone marrow adipose tissue in response to feeding and fasting.

JCI Insight 2021 Jun 22;6(12). Epub 2021 Jun 22.

Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

BACKGROUNDAdipocytes were long considered inert components of the bone marrow niche, but mouse and human models suggest bone marrow adipose tissue (BMAT) is dynamic and responsive to hormonal and nutrient cues.METHODSIn this study of healthy volunteers, we investigated how BMAT responds to acute nutrient changes, including analyses of endocrine determinants and paracrine factors from marrow aspirates. Study participants underwent a 10-day high-calorie protocol, followed by a 10-day fast.RESULTSWe demonstrate (a) vertebral BMAT increased significantly during high-calorie feeding and fasting, suggesting BMAT may have different functions in states of caloric excess compared with caloric deprivation; (b) ghrelin, which decreased in response to high-calorie feeding and fasting, was inversely associated with changes in BMAT; and (c) in response to high-calorie feeding, resistin levels in the marrow sera, but not the circulation, rose significantly. In addition, TNF-α expression in marrow adipocytes increased with high-calorie feeding and decreased upon fasting.CONCLUSIONHigh-calorie feeding, but not fasting, induces an immune response in bone marrow similar to what has been reported in peripheral adipose tissue. Understanding the immunomodulatory regulators in the marrow may provide further insight into the homeostatic function of this unique adipose tissue depot.FUNDINGNIH grant R24 DK084970, Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH, award UL 1TR002541), and NIH grants P30 DK040561 and U19 AG060917S1.
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http://dx.doi.org/10.1172/jci.insight.138636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262500PMC
June 2021

Rates and Risk Factors for Interval Gastric Cancers at Screening Gastroscopy.

Turk J Gastroenterol 2021 02;32(2):194-202

Department of Internal Medicine, Hanyang University School of Medicine, Seoul, South Korea.

Backgrounds/aims: Interval gastric cancers (GCs) can be encountered during screening gastroscopy. This study investigated the rate of interval GCs and their risk factors.

Materials And Methods: We retrospectively investigated subjects who underwent screening gastroscopy from 2005 to 2017 in a university hospital and were diagnosed with GC. Subjects were grouped based on their endoscopic images and descriptive results into interval GC and initially diagnosed GC groups. Interval GCs were defined when endoscopic results within the previous 3 years were negative for GC. The clinico-pathological characteristics of the groups and risk factors for interval GCs were evaluated.

Results: Of 54 724 subjects who underwent screening gastroscopy, 234 were diagnosed with GC, of which 43 were interval GCs. The rate of interval GCs was 18.4% (43/234, mean age 61.6 years). Interval GCs were smaller than initially diagnosed GCs (1.6 vs 1.9 cm, P = .011). They were located in the low-to-mid-body in 44.2%, antrum in 48.8%, and high body and cardia in 7%. Their observation time was shorter (248.74 vs 410.64 sec, P = .032). In multivariate analysis, they were associated with short observation time (odds ratio [OR] 0.99, 95% CI 0.994-0.998, P < .001) and location in the low-to-mid-body (OR 2.12, 95% CI 1.071-4.181, P = .031), although differentiation, ulcerated type, metaplasia, Helicobacter pylori infection, and endoscopists' experience were not associated with interval GCs.

Conclusions: The rate of interval GCs was significant during screening gastroscopy. They might be reduced by increasing observation time, focusing on smaller lesions, and observing the low-to-mid-body of the stomach more carefully.
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http://dx.doi.org/10.5152/tjg.2021.20129DOI Listing
February 2021

The Asian plethodontid salamander preserves historical genetic imprints of recent northern expansion.

Sci Rep 2021 04 28;11(1):9193. Epub 2021 Apr 28.

Research Institute for Veterinary Science and Conservation Genome Resource Bank for Korean Wildlife, College of Veterinary Medicine, Seoul National University, Seoul, 08826, South Korea.

The Korean Peninsula, located at the southern tip of Northeast Asia, has never been covered by ice sheets and was a temperate refugium during the Pleistocene. Karsenia koreana, the sole Asian plethodontid salamander species, occurs only on the southern half of the Korean Peninsula and is thought to have found various climatic refugia. Despite its phylogenetic and biogeographic importance, no population-level genetic analysis has been performed on this species. Here we study the population genetic structure of K. koreana using mitochondrial and microsatellite loci to understand the recent historical dispersion process that shaped its current distribution. Overall, the genetic distance between populations correlated well with the spatial distance, and the genetic structure among populations showed signs of a unilateral northward expansion from a southernmost refugium population. Given the distinct genetic structure formed among the populations, the level of historical gene flow among populations appears to have been very low. As the estimated effective population size of K. koreana was also small, these results suggest that the small, restricted populations of K. koreana are extremely vulnerable to environmental changes that may require high levels of genetic diversity to cope with. Thus, special management strategies are needed to preserve these remnant populations.
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http://dx.doi.org/10.1038/s41598-021-88238-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080585PMC
April 2021

Association of adverse prenatal exposure burden with child psychopathology in the Adolescent Brain Cognitive Development (ABCD) Study.

PLoS One 2021 28;16(4):e0250235. Epub 2021 Apr 28.

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America.

Objective: Numerous adverse prenatal exposures have been individually associated with risk for psychiatric illness in the offspring. However, such exposures frequently co-occur, raising questions about their cumulative impact. We evaluated effects of cumulative adverse prenatal exposure burden on psychopathology risk in school-aged children.

Methods: Using baseline surveys from the U.S.-based Adolescent Brain and Cognitive Development (ABCD) Study (7,898 non-adopted, unrelated children from 21 sites, age 9-10, and their primary caregivers), we examined 8 retrospectively-reported adverse prenatal exposures in relation to caregiver-reported total and subscale Child Behavior Checklist (CBCL) scores. We also assessed cumulative effects of these factors on CBCL total as a continuous measure, as well as on odds of clinically significant psychopathology (CBCL total ≥60), in both the initial set and a separate ABCD sample comprising an additional 696 sibling pairs. Analyses were conducted before and after adjustment for 14 demographic and environmental covariates.

Results: In minimally and fully adjusted models, 6 exposures (unplanned pregnancy; maternal alcohol, marijuana, and tobacco use early in pregnancy; pregnancy complications; and birth complications) independently associated with significant but small increases in CBCL total score. Among these 6, none increased the odds of crossing the threshold for clinically significant symptoms by itself. However, odds of exceeding this threshold became significant with 2 exposures (OR = 1.86, 95% CI 1.47-2.36), and increased linearly with each level of exposure (OR = 1.39, 95% CI 1.31-1.47), up to 3.53-fold for ≥4 exposures versus none. Similar effects were observed in confirmatory analysis among siblings. Within sibling pairs, greater discordance for exposure load associated with greater CBCL total differences, suggesting that results were not confounded by unmeasured family-level effects.

Conclusion: Children exposed to multiple common, adverse prenatal events showed dose-dependent increases in broad, clinically significant psychopathology at age 9-10. Fully prospective studies are needed to confirm and elaborate upon this pattern.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250235PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081164PMC
September 2021

Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease.

Clin Infect Dis 2021 08;73(4):621-630

Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Background: The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis modulates critical metabolic pathways; however, little is known regarding effects of augmenting pulsatile GH secretion on immune function in humans. This study used proteomics and gene set enrichment analysis to assess effects of a GH releasing hormone (GHRH) analog, tesamorelin, on circulating immune markers and liver tissue in people with human immunodeficiency virus (HIV) (PWH) and nonalcoholic fatty liver disease (NAFLD).

Methods: 92 biomarkers associated with immunity, chemotaxis, and metabolism were measured in plasma samples from 61 PWH with NAFLD who participated in a double-blind, randomized trial of tesamorelin versus placebo for 12 months. Gene set enrichment analysis was performed on serial liver biopsies targeted to immune pathways.

Results: Tesamorelin, compared to placebo, decreased interconnected proteins related to cytotoxic T-cell and monocyte activation. Circulating concentrations of 13 proteins were significantly decreased, and no proteins increased, by tesamorelin. These included 4 chemokines (CCL3, CCL4, CCL13 [MCP4], IL8 [CXCL8]), 2 cytokines (IL-10 and CSF-1), and 4 T-cell associated molecules (CD8A, CRTAM, GZMA, ADGRG1), as well as ARG1, Gal-9, and HGF. Network analysis indicated close interaction among the gene pathways responsible for these proteins, with imputational analyses suggesting down-regulation of a closely related cluster of immune pathways. Targeted transcriptomics using liver tissue confirmed a significant end-organ signal of down-regulated immune activation pathways.

Conclusions: Long-term treatment with a GHRH analog reduced markers of T-cell and monocyte/macrophage activity, suggesting that augmentation of the GH axis may ameliorate immune activation in an HIV population with metabolic dysregulation, systemic and end organ inflammation. Clinical Trials Registration. NCT02196831.
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http://dx.doi.org/10.1093/cid/ciab019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366828PMC
August 2021

The Impact of Vitamin D on Response to Anti-tumor Necrosis Factor-α Therapy in Children With Inflammatory Bowel Disease.

J Pediatr Gastroenterol Nutr 2021 05;72(5):e125-e131

Division of Pediatric Gastroenterology, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA.

Objectives: Experimental studies have shown that vitamin D has an immunomodulatory effect on the innate and adaptive immune systems. Associations between vitamin D deficiency and development or progression of inflammatory bowel diseases (IBDs) are reported, but a cause-and-effect relationship between pretreatment 25 hydroxyvitamin D [25(OH)D] levels and response to anti-tumor necrosis factor-α (anti-TNF) therapy is not established.

Methods: This retrospective study evaluated pediatric IBD patients who had 25(OH)D levels drawn within 3 months of initiating infliximab and/or adalimumab treatment. Demographic features, Paris classification, baseline 25(OH)D levels, disease activity, and laboratory results before and after 3 months of anti-TNF therapy were collected. The interaction between vitamin D insufficiency at induction and lack of response to anti-TNF therapy at 3 months was determined.

Results: Of the 383 patients, 76 met inclusion criteria. Sixty-five patients (85.5%) had Crohn disease (CD) and 11 (14.5%) had ulcerative colitis. Seven patients had 25(OH)D levels obtained during both infliximab and adalimumab induction; hence 83 subjects were evaluated (infliximab: 70 patients, adalimumab: 13 patients). 25(OH)D <30 ng/mL was found in 55 of 83 (66.3%) subjects. There were no differences in gender, IBD type, disease activity scores between vitamin D-sufficient and vitamin D-insufficient groups. In CD, proximal gastrointestinal tract inflammation was associated with vitamin D insufficiency (P = 0.019), but other Paris classification parameters and laboratory results were similar in 2 groups. Early termination of anti-TNF therapy was significantly higher in patients who had vitamin D insufficiency (14.5% vs 0%, P = 0.034).

Conclusions: Vitamin D insufficiency before anti-TNF treatment may result in poor response to induction therapy.
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http://dx.doi.org/10.1097/MPG.0000000000003064DOI Listing
May 2021

Efficacy and Safety of Rebamipide versus Its New Formulation, AD-203, in Patients with Erosive Gastritis: A Randomized, Double- Blind, Active Control, Noninferiority, Multicenter, Phase 3 Study.

Gut Liver 2021 Apr 7. Epub 2021 Apr 7.

Division of Gastroenterology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea.

Background/aims: : The mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of Mucosta (rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in treating erosive gastritis.

Methods: This double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups: AD-203 twice daily or Mucosta thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; Mucosta, n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; Mucosta, n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated.

Results: According to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta-treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta-treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was -4.01% (95% confidence interval [CI], -13.09% to 5.06%) in the ITT analysis and -4.44% (95% CI, -13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 Mucosta-treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates.

Conclusions: The new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (Mucosta) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.
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http://dx.doi.org/10.5009/gnl20338DOI Listing
April 2021

Long-term outcomes of endoscopic resection followed by additional surgery after non-curative resection in undifferentiated-type early gastric cancer: a nationwide multi-center study.

Surg Endosc 2021 Apr 6. Epub 2021 Apr 6.

Center for Gastric Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi, 10408, South Korea.

Background: Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment.

Methods: We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared.

Results: Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively.

Conclusions: ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC.
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http://dx.doi.org/10.1007/s00464-021-08464-4DOI Listing
April 2021

Long-term Outcomes of Undifferentiated-Type Early Gastric Cancer with Positive Horizontal Margins after Endoscopic Resection.

Gut Liver 2021 09;15(5):723-731

Center for Gastric Cancer, National Cancer Center, Goyang, Korea.

Background/aims: This study examined the long-term outcomes of undifferentiated-type early gastric cancer (UD EGC) with positive horizontal margins (HMs) after endoscopic resection (ER) and compared them between additional surgery and nonsurgical management.

Methods: From 2005 to 2015, a total of 1,124 patients with UD EGC underwent ER at 18 tertiary hospitals in Korea. Of them, 92 patients with positive HMs as the only noncurative factor (n=25) or with both positive HMs and tumor size >2 cm (n=67) were included. These patients underwent additional surgery (n=40), underwent additional endoscopic treatment (n=6), or were followed up without further treatment (n=46).

Results: No lymph node (LN) metastasis was found in patients who underwent additional surgery. During a median follow-up of 57.7 months (interquartile range, 27.6 to 68.8 months), no LN or distant metastases or gastric cancer-related deaths occurred in the overall cohort. At baseline, the residual cancer rate was 57.8% (26/45) after additional surgery or ER. The 5-year local recurrence rate was 33.6% among patients who were followed up without additional treatment. The 5-year overall survival rates were 95.0% and 87.8% after additional surgery and nonsurgical management (endoscopic treatment or close follow-up), respectively (log-rank p=0.224). In the multivariate Cox regression analysis, nonsurgical management was not associated with an increased risk of mortality.

Conclusions: UD EGC with positive HMs after ER may have favorable long-term outcomes and a very low risk of LN metastasis. Nonsurgical management may be suggested as an alternative, particularly for patients with old age or chronic illness.
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http://dx.doi.org/10.5009/gnl20291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444099PMC
September 2021

Earlier Detection of Glaucoma Progression Using High-Density 3-Dimensional Spectral-Domain OCT Optic Nerve Volume Scans.

Ophthalmol Glaucoma 2021 Mar 25. Epub 2021 Mar 25.

Department of Ophthalmology, Glaucoma Service, Massachusetts Eye and Ear, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, 2-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and 3-dimensional (3D) spectral-domain (SD) OCT neuroretinal rim measurements.

Design: Prospective, longitudinal cohort study.

Participants: One hundred twenty-four eyes of 124 patients with open-angle glaucoma.

Methods: Over a 5-year period, 124 patients with open-angle glaucoma underwent yearly DP, VF testing, SD OCT RNFL thickness scans, and optic nerve volume scans (Spectralis; Heidelberg Engineering), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or nonglaucoma progressors using event-based analysis. Progression by DP and VF testing occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if change of more than test-retest variability was observed. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa Coefficients were used to measure agreement of progressing eyes among methods.

Main Outcome Measures: Time to glaucoma progression among all 4 methods.

Results: Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4%) compared with DP (16.1%; P < 0.001) and global RNFL thickness (15.3%; P < 0.001). Global MDB thickness detected glaucoma progression earlier than either DP (23 months vs. 44 months; P < 0.001) or global RNFL thickness (23 months vs. 33 months; P < 0.001). Among MDB progressing eyes, 46.2% were confirmed simultaneously or later by other conventional methods. Agreement of glaucoma-progressing eyes for all 4 methods in paired fashion were slight to fair (κ = 0.095-0.300).

Conclusions: High-density 3D SD OCT neuroretinal rim measurements detected glaucoma progression approximately 1 to 2 years earlier compared with current clinically available structural tests (i.e., DP and 2D RNFL thickness measurements).
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http://dx.doi.org/10.1016/j.ogla.2021.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463625PMC
March 2021

Prediction model for curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

Surg Endosc 2021 Mar 16. Epub 2021 Mar 16.

Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.

Background: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC); however, its curative resection rate is low for undifferentiated-type EGC. We developed and externally validated a prediction model for curative ESD of undifferentiated-type EGC.

Methods: In this cross-sectional study, we included 448 patients who underwent ESD for undifferentiated-type EGC at 18 hospitals in Korea between 2005 and 2015 in the development cohort and 1342 patients who underwent surgery at two hospitals in the validation cohort. A prediction model was developed using the logistic regression model.

Results: Endoscopic tumor size 1-2 cm (odds ratio [OR], 2.40; 95% confidence interval [CI] 1.54-3.73), tumor size > 2 cm (OR, 14.00; 95% CI 6.81-28.77), and proximal tumor location from the lower to upper third of the stomach (OR, 1.45; 95% CI 1.03-2.04) were independent predictors of non-curative ESD. A six-score prediction model was developed by assigning points to endoscopic tumor size > 2 cm (five points), tumor size 1-2 cm (two points), upper third location (two points), and middle third location (one point). The rate of curative ESD ranged from 70.6% (score 0) to 11.6% (score 5) with an area under the receiver operating characteristic curve (AUC) of 0.720 (95% CI 0.673-0.766). The model also showed good performance in the validation cohort (AUC, 0.775; 95% CI 0.748-0.803).

Conclusions: This six-score prediction model may help in predicting curative ESD and making informed decisions about the treatment selection between ESD and surgery for undifferentiated-type EGC.
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http://dx.doi.org/10.1007/s00464-021-08426-wDOI Listing
March 2021

Evaluation of Release Maneuvers After Airway Reconstruction.

Ann Thorac Surg 2021 Mar 6. Epub 2021 Mar 6.

Division of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Background: Airway release (AR) maneuvers performed during airway resection to reduce anastomotic tension have not been thoroughly studied.

Methods: This study retrospectively analyzed consecutive resections for postintubation stenosis (PITS) and primary tracheal neoplasms (PTNs) at Massachusetts General Hospital (Boston, MA). Anastomotic complications were defined as stenosis, separation, necrosis, granulation tissue, and air leak. Logistic regression modeling was used to identify factors associated with AR and adverse outcome.

Results: From 1993 to 2019, 545 patients with PITS (375; 68.8%) and PTNs (170; 31.2%) underwent laryngotracheal, tracheal, or carinal (resections and reconstructions; 5.7% (31 of 545) were reoperations. AR was performed in 11% (60 of 545): in 3.8% of laryngotracheal resections (6 of 157; all laryngeal), in 9.8% of tracheal resections (34 of 347; laryngeal, 12, and hilar, 22), and in 49% of carinal resections (20 of 41; laryngeal, 1, and hilar, 19). Mean resected length was 3.5 cm (range, 1to- 6.3 cm) with AR and 3.0 cm (range, 0.8 to 6.5 cm) without AR (P < .01). Operative mortality was 0.7% (4 of 545); all 4 anastomoses were intact until death. Anastomotic complications were present in 5% of patients who underwent AR (3 of 60) and in 9.3% (45 of 485) of patients who did not. AR was associated with resection length of 4 cm or longer (odds ratio [OR], 6.15; 95% confidence interval [CI], 1.37 to 27.65), PTNs (OR, 7.81; 95% CI, 3.31 to 18.40), younger age (OR, 0.96; 95% CI, 0.94 to 0.98), and lung resection (OR, 6.09; 95% CI, 1.33 to 27.90). Anastomotic complications in patients with tracheal anastomoses were associated with preexisting tracheostomy (OR, 2.68; 95% CI, 1.50 to 4.80), but not release.

Conclusions: Tracheal reconstruction succeeds, even when anastomotic tension requires AR. Because intraoperative assessment may underestimate tension, lowering the threshold for AR seems prudent, particularly in patients with diabetes.
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http://dx.doi.org/10.1016/j.athoracsur.2021.03.001DOI Listing
March 2021

Is There Pathological Uniformity between the Periphery and Center of a Gastrointestinal Stromal Tumor?

J Clin Med 2021 Feb 10;10(4). Epub 2021 Feb 10.

Department of Gastroenterology, Hanyang University Hospital, Seoul 04763, Korea.

Background: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors and have some malignant potential. Mitotic count is important for predicting the malignant potential of GISTs. Proper treatment of GISTs requires accurate pathological diagnosis. In general, endoscopic ultrasound-guided fine-needle aspiration and deep biopsy are used for pathological diagnosis of GIST before making decisions about surgery. This study sought to evaluate the pathological uniformity of gastric GISTs for mitotic index of the center and periphery of the GIST.

Methods: We retrospectively reviewed the data of 37 gastric GIST patients who underwent wedge resection at Hanyang University Hospital. We used Armed Forces Institute of Pathology criteria to classify gastric GISTs. To determine the pathological uniformity of gastric GISTs, we compared GIST risk stratification between the center and periphery of GISTs.

Results: The mean size of GISTs was 3.56 ± 2.10 cm. Three lesions were located in the antrum, 11 in the fundus, 9 in the cardia, and 14 in the body. The mean age of patients was 58.65 ± 9.44 years; 18 patients were male and 19 were female. Thirty-five patients (94.6%) showed the same level of risk stratification between the center and periphery of gastric GISTs, while two patients (5.4%) presented different levels of risk between the two sites. No significant difference in mitotic count was observed between the two sites (kappa value = 0.863; = 0.001).

Conclusions: Mitotic index category (either more than five mitoses per high-power field or five or fewer mitoses per high-power field) of GISTs showed good concurrence between the center and periphery.
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http://dx.doi.org/10.3390/jcm10040687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916709PMC
February 2021

Microsatellite characterization and development of unified STR panel for big cats in captivity: a case study from a Seoul Grand Park Zoo, Republic of Korea.

Mol Biol Rep 2021 Feb 10;48(2):1935-1942. Epub 2021 Feb 10.

Conservation Genome Resource Bank for Korean Wildlife and Research Institute for Veterinary Science, Seoul National University College of Veterinary Medicine, 1 Gwanak-gu, Gwanak-ro, Seoul, Republic of Korea.

The zoos manage small populations of endangered big cat species like tiger, lion, and leopard for display, research, and conservation breeding. Genetic management of these populations is essential to ensure long term survival and conservation utility. Here we propose a simple and cost effective microsatellite based protocol for the genetic management of captive big cats. We sampled 36 big cat individuals from Seoul Grand Park Zoo (Republic of Korea) and amplified 33 published microsatellite loci. Overall, allelic richness and gene diversity was found highest for leopards, followed by lions and tigers. Twelve of the thirty-three markers showed a high degree of polymorphism across all target species. These microsatellites provide a high degree of discrimination for tiger (1.45 × 10), lion (1.54 × 10), and leopard (1.88 × 10) and thus can be adopted for the genetic characterization of big cats in accredited zoos globally. During captive breeding, zoo authorities rely on pedigree records maintained in studbooks to ensure mating of genetically fit unrelated individuals. Several studies have reported errors in studbook records of big cat species. Microsatellites are simple and cost effective tool for DNA fingerprinting, estimation of genetic diversity, and paternity assessment. Our unified microsatellite panel (12-plex) for big cats is efficient and can easily be adopted by zoo authorities for regular population management.
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http://dx.doi.org/10.1007/s11033-021-06202-6DOI Listing
February 2021

COVID-19 Diagnostic Clinical Decision Support: a Pre-Post Implementation Study of CORAL (COvid Risk cALculator).

Clin Infect Dis 2021 Feb 10. Epub 2021 Feb 10.

Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.

Background: Isolation of hospitalized persons under investigation (PUIs) for COVID-19 reduces nosocomial transmission risk. Efficient PUI evaluation is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs.

Methods: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to Infectious Diseases (ID) physician review. Pre-CORAL, ID physicians reviewed all PUI records to guide workup and precautions. Post-CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeat SARS-CoV-2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work-hours, using linear and logistic regression, adjusted for COVID-19 incidence.

Results: Fewer PUIs underwent repeat testing after an initial negative NAAT post-CORAL than pre-CORAL (54% vs. 67%; aOR 0.53, 95% CI: 0.44-0.63, p<0.01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference: -7.4 [SE 0.8] hours/patient; p<0.01), total duration of PUI status (adjusted difference: -19.5 [SE 1.9] hours/patient; p<0.01), and average ID physician work-hours (adjusted difference: -57.4 [SE 2.0] hours/day; p<0.01). No patients had a positive NAAT within 7 days after discontinuation of precautions via CORAL.

Conclusions: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.
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http://dx.doi.org/10.1093/cid/ciab111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929052PMC
February 2021
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