Krystle Man-Chin Leung, MD

All Publications

• Feeding intolerance in critically ill patients with COVID-19. Clinical nutrition (Edinburgh, Scotland) Liu, R., Paz, M., Siraj, L., Boyd, T., Salamone, S., Lite, T. V., Leung, K. M., Chirinos, J. D., Shang, H. H., Townsend, M. J., Rho, J., Ni, P., Ranganath, K., Violante, A. D., Zhao, Z., Silvernale, C., Ahmad, I., Krasnow, N. A., Barnett, E. S., Harisinghani, M., Kuo, B., Black, K. E., Staller, K. 2022; 41 (12): 3069-3076

  Abstract

  Early reports suggest significant difficulty with enteral feeding in critically ill COVID-19 patients. This study aimed to characterize the prevalence, clinical manifestations, and outcomes of feeding intolerance in critically ill patients with COVID-19.We examined 323 adult patients with COVID-19 admitted to the intensive care units (ICUs) of Massachusetts General Hospital between March 11 and June 28, 2020 who received enteral nutrition. Systematic chart review determined prevalence, clinical characteristics, and hospital outcomes (ICU complications, length of stay, and mortality) of feeding intolerance.Feeding intolerance developed in 56% of the patients and most commonly manifested as large gastric residual volumes (83.9%), abdominal distension (67.2%), and vomiting (63.9%). Length of intubation (OR 1.05, 95% CI 1.03-1.08), ≥1 GI symptom on presentation (OR 0.76, 95% CI 0.59-0.97), and severe obesity (OR 0.29, 95% CI 0.13-0.66) were independently associated with development of feeding intolerance. Compared to feed-tolerant patients, patients with incident feeding intolerance were significantly more likely to suffer cardiac, renal, hepatic, and hematologic complications during their hospitalization. Feeding intolerance was similarly associated with poor outcomes including longer ICU stay (median [IQR] 21.5 [14-30] vs. 15 [9-22] days, P < 0.001), overall hospitalization time (median [IQR] 30.5 [19-42] vs. 24 [15-35], P < 0.001) and in-hospital mortality (33.9% vs. 16.1%, P < 0.001). Feeding intolerance was independently associated with an increased risk of death (HR 3.32; 95% CI 1.97-5.6).Feeding intolerance is a frequently encountered complication in critically ill COVID-19 patients in a large tertiary care experience and is associated with poor outcomes.

  View details for DOI 10.1016/j.clnu.2021.03.033

  View details for PubMedID 33934924

  View details for PubMedCentralID PMC8007186

• Changes in Orders for Life-Sustaining Treatment in Patients Requiring Prolonged Mechanical Ventilation JOURNAL OF PALLIATIVE MEDICINE Leung, K. M. M., McCoy, T. H. H., Rubin, E. B. B. 2022: 1850-1856

  Abstract

  Background: Growing numbers of acute critical illness survivors experience chronic critical illness (CCI) marked by prolonged dependence on life support, delirium, and/or disability. There is minimal recent data on treatment limitations in CCI. Objectives: To evaluate the natural history of changes in orders for life-sustaining treatment (OLST) in patients requiring prolonged mechanical ventilation. Design: Retrospective cohort study of 410 patients who received tracheostomy in an intensive care unit for prolonged respiratory failure. Results: Three hundred twenty-four patients had one OLST throughout the admission, with no limitations on prearrest life-sustaining treatment or cardiopulmonary resuscitation. The 86 patients who underwent at least one change in OLST were older, had longer admissions, were more likely to be deceased at hospital discharge, and were more likely to have received specialty palliative care. Thirty percent of OLST changes occurred in the last week of admission. Conclusions: OLST occur infrequently and late in patients with CCI.

  View details for DOI 10.1089/jpm.2022.0194

  View details for Web of Science ID 000892073800001

  View details for PubMedID 36201303

• On Isolation: Gowns and Glass. Journal of the American Geriatrics Society Leung, K. M. 2020; 68 (5): 930-931

  View details for DOI 10.1111/jgs.16463

  View details for PubMedID 32267532

  View details for PubMedCentralID PMC7262267

• Translation of adapting quantitative CT data from research to local clinical practice: validation evaluation of fully automated procedures to provide lung volumes and percent emphysema. Journal of medical imaging (Bellingham, Wash.) Leung, K. M., Curran-Everett, D., Regan, E. A., Lynch, D. A., Jacobson, F. L. 2020; 7 (2): 022404

  Abstract

  Current clinical chest CT reporting includes limited qualitative assessment of emphysema with rare mention of lung volumes and limited reporting of emphysema, based upon retrospective review of CT reports. Quantitative CT analysis performed in COPDGene and other research cohorts utilize semiautomated segmentation procedures and well-established research method (Thirona). We compared this reference QCT data with fully automated QCT analysis that can be obtained at the time of CT scan and sent to PACS along with standard chest CT images. 164 COPDGene® cohort study subjects enrolled at Brigham and Women's Hospital had baseline and 5-year follow-up CT scans. Subjects included 17 nonsmoking controls, 92 smokers with normal spirometry, 15 preserved ratio impaired spirometry (PRISm) patients, 12 GOLD 1, 20 GOLD 2, and 8 GOLD 3-4. 97% ( n = 319 ) of clinical reports did not mention lung volumes, and 14% ( n = 46 ) made no mention of emphysema. Total lung volumes determined by the fully automated algorithm were consistently 47 milliliters (ml) less than the Thirona reference value for all subjects (95% confidence interval - 62 to - 32    ml ). Percent emphysema values were equivalent to the Thirona reference values. Well-established research reference data can be used to evaluate and validate automated QCT software. Validation can be repeated as software is updated.

  View details for DOI 10.1117/1.JMI.7.2.022404

  View details for PubMedID 31824985

  View details for PubMedCentralID PMC6903769

• Trends in Solid Tumor Incidence in Ukraine 30 Years After Chernobyl. Journal of global oncology Leung, K. M., Shabat, G., Lu, P., Fields, A. C., Lukashenko, A., Davids, J. S., Melnitchouk, N. 2019; 5: 1-10

  Abstract

  There is limited knowledge of the long-term health effects of the Chernobyl nuclear power plant accident that occurred more than 30 years ago in Ukraine. This study describes trends in the incidence of solid organ malignancy in Ukraine and the five regions most affected by the radioactive fallout.The National Cancer Registry of Ukraine was queried for age-standardized incidence rates (ASIRs) of solid organ malignancy in Ukraine and the regions of Kyiv, Chernihiv, Zhytomyr, Rivne, and Volyn covering the period of 1999 to 2016. Joinpoint analysis was used to calculate the average annual percentage of change.The highest burdens of cancer incidence in Ukraine were seen in the lung, stomach, breast, and prostate. We observed significant increases in the ASIRs of colon (average annual percentage of change, 1.5 [95% CI, 1.3 to 1.7]), rectal (0.9 [95% CI, 0.6 to 1.2]), kidney (2.3 [95% CI, 1.8 to 2.9]), thyroid (4.2 [95% CI, 3.1 to 5.3]), breast (1 [95% CI, 0.6 to 1.4]), cervical (0.7 [95% CI, 0.3 to 1.2]), and prostate (3.9 [95% CI, 3.6 to 4.2]) cancers, with decreases in stomach (-2.4 [95% CI, -2.5 to -2.3]) and lung (-1.8 [95% CI, -2.1 to -1.5]) cancers. ASIRs in the affected regions were similar to nationwide rates, with the exception of those for Kyiv.The incidence rates of many solid organ malignancies in Ukraine are rising. However, the rates of solid organ malignancy in the five regions most affected by fallout did not substantially differ from national patterns, with the exception of those for Kyiv. Ongoing monitoring of cancer incidence in Ukraine is necessary to understand how best to decrease disease burden nationwide and to elucidate the causes of regional variations in ASIRs, such as access to diagnostics and environmental exposures.

  View details for DOI 10.1200/JGO.19.00099

  View details for PubMedID 31454285

  View details for PubMedCentralID PMC6733202

• Outcomes of Abdominal Surgery in Patients With Mechanical Ventricular Assist Devices: A Multi-institutional Study. Annals of surgery Leung, K. M., Kiely, M. X., Kimbrell, A., Asban, A., Kelley, R., Bleday, R., Davids, J. S., Melnitchouk, N. 2019; 269 (4): 774-777

  Abstract

  The aim of this study was to examine the outcomes of elective and emergent abdominal operations performed in end-stage heart failure patients supported with ventricular assist devices (VADs).With the growing volume of end-stage heart failure patients receiving VADs, an increasing number of these patients require surgery for noncardiac pathology. There is a paucity of studies on the safety of abdominal operations in this population.We performed a retrospective chart review across 3 hospitals of patients with VADs who underwent abdominal surgeries between 2003 and 2015. We used Chi-square, Fisher exact, and Mann-Whitney U tests for comparison of elective and emergent cases.Fifty-seven patients underwent 63 operations, of which 23 operations were elective, 24 were emergent, and 16 were emergently performed in the same admission as VAD placement and analyzed separately. Patients undergoing elective versus emergent procedures had similar comorbidities (Charlson score 2.9 vs 3.0). 43% versus 32% of patients had VADs as a destination therapy. Although perioperative anticoagulation approach was variable, holding warfarin and starting heparin/enoxaparin/bivalirudin bridge was most common (65% vs 54%). Although 2-fold higher in the emergent group (50 vs 100 mL, P = 0.06), median estimated blood loss was low. Postoperative bleeding requiring transfusion was not very common (13% vs 8%), whereas rate of ischemic cerebrovascular accident (4% each) and venous thromboembolism was low (0% vs 13%, P = 0.23). Thirty-day mortality rate was 4% versus 17%, P = 0.19.VAD patients have an acceptable risk profile for abdominal surgery.

  View details for DOI 10.1097/SLA.0000000000002513

  View details for PubMedID 28885501

• A natural killer T-cell subset that protects against airway hyperreactivity. The Journal of allergy and clinical immunology Chuang, Y. T., Leung, K., Chang, Y. J., DeKruyff, R. H., Savage, P. B., Cruse, R., Benoit, C., Elewaut, D., Baumgarth, N., Umetsu, D. T. 2019; 143 (2): 565-576.e7

  Abstract

  Infection of suckling mice with influenza virus expands a CD4-CD8- double-negative (DN) natural killer T (NKT) cell subpopulation that protects the mice as adults against allergen-induced airway hyperreactivity (AHR). However, this NKT cell subset has not been characterized, and the underlying mechanisms of protection remain unknown.We characterized this specific NKT cell subpopulation that developed during influenza infection in neonatal mice and that suppressed the subsequent development of AHR.A cell-surface marker was identified by comparing the mRNA expression profile of wild-type CD4+ NKT cells with that of suppressive Vα14 DN NKT cells. The marker-enriched NKT cell subset was then analyzed for its cytokine profile and its suppressive in vitro and in vivo abilities.We showed that DN NKT cells with high CD38 expression produced IFN-γ, but not IL-17, IL-4, or IL-13, and inhibited development of AHR through contact-dependent suppression of helper CD4 T-cell proliferation. The NKT subset expanded in the lungs of neonatal mice after infection with influenza and also after treatment of neonatal mice with Nu-α-GalCer, which effectively increased DN CD38hi NKT cell numbers.These results suggest that early/neonatal exposure to infection or antigen challenge affects subsequent lung immunity by altering the cellular composition of cells in the lung and that some subsets of NKT cells suppress AHR. These results provide a possible mechanism by which prior infections can protect against the development of allergic asthma and might be further explored as a protective measure for young children.

  View details for DOI 10.1016/j.jaci.2018.03.022

  View details for PubMedID 29852257

• Blockade of Repulsive guidance molecule b (RGMb) inhibits allergen-induced airways disease. The Journal of allergy and clinical immunology Yu, S., Leung, K. M., Kim, H., Umetsu, S. E., Xiao, Y., Albacker, L. A., Lee, H., Umetsu, D. T., Freeman, G. J., DeKruyff, R. H. 2019

  Abstract

  BACKGROUND: Allergic asthma causes morbidity in many individuals and novel precision-directed treatments would be valuable.OBJECTIVE: To examine the role of a novel innate molecule, repulsive guidance molecule b (RGMb), in murine models of allergic asthma.METHODS: In models of allergic asthma using OVA or cockroach allergen, mice were treated with anti-RGMb or control mAb and examined for airway inflammation and airway hyperreactivity (AHR), a cardinal feature of asthma. The mechanisms by which RGMb causes airways disease were also examined.RESULTS: We found that blockade of RGMb by treatment with anti-RGMb mAb effectively blocked the development of airway inflammation and AHR. Importantly, blockade of RGMb completely blocked the development of airway inflammation and AHR, even if treatment occurred only during the challenge (effector) phase. IL-25 played an important role in these models of asthma, since IL-25 receptor deficient mice failed to develop disease. RGMb was expressed primarily by innate cells in the lungs, including bronchial epithelial cells (known producers of IL-25), activated eosinophils and interstitial macrophages, which in the inflamed lung expressed the IL-25 receptor and produced IL-5 and IL-13. We also found that NEO1, the canonical receptor for RGMb, was expressed by interstitial macrophages and bronchial epithelial cells in the inflamed lung, suggesting that an innate RGMb-NEO1 axis might modulate allergic asthma.CONCLUSIONS: These results demonstrate an important role for a novel innate pathway in regulating type 2 inflammation in allergic asthma, involving RGMb and RGMb-expressing cells such as interstitial macrophages and bronchial epithelial cells. Moreover, targeting this previously unappreciated innate pathway might provide an important treatment option for allergic asthma.

  View details for PubMedID 30703386

• Colorectal Cancer in Ukraine: Regional Disparities and National Trends in Incidence, Management, and Mortality. Journal of global oncology Melnitchouk, N., Shabat, G., Lu, P., Lyu, H., Scully, R., Leung, K., Jarman, M., Lukashenko, A., Kolesnik, O. O., Goldberg, J., Davids, J. S., Bleday, R. 2018; 4

  Abstract

  The incidence of colorectal cancer (CRC) is increasing worldwide, and the greatest increase is in low- to middle-income countries, such as Ukraine. Better knowledge of epidemiology of CRC in Ukraine is needed to understand how best to decrease the burden of disease.The National Cancer Registry of Ukraine (NCRU) was queried for CRC incidence, mortality, stage, and treatment in Ukraine and assessed for regional variation from 1999 to 2015. Joinpoint analysis was used to analyze the trends.The incidence of colon cancer increased from 10.6 to 13.3 occurrences per 100,000, which provided an average annual percent change (AAPC) of 1.48 (95% CI, 1.3 to 1.7; P < .05). The incidence of rectal and anal cancers also increased from 9.9 to 11.5 occurrences per 100,000, which provided an AAPC of 1.0 (95% CI, 0.8 to 1.3; P < .05). Mortality remained the same (AAPC, 0.1; 95% CI, -0.3 to 0.2; P = .4). The proportion of patients who received cancer-specific treatment increased from 54.6% to 68.5% for colon cancer and from 61% to 74.4% for rectal and anal cancers. Overall, 34.5% of patients with colon cancer and 27.5% of patients with rectal cancer died within a year of diagnosis in 2015. Great regional variations in 1-year mortality and treatment received were identified.The incidence of CRC in Ukraine is increasing. Despite stable mortality rates, many do not receive cancer-specific treatment, and a large proportion of patients die within a year of diagnosis. These findings illustrate the need to promote establishment of a screening program and to improve access to cancer-specific therapy in Ukraine.

  View details for DOI 10.1200/JGO.18.00145

  View details for PubMedID 30354936

  View details for PubMedCentralID PMC6657623