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Article ; Online: COVID-19 Associated with Cryptococcosis: A New Challenge during the Pandemic.

Chan, Khee-Siang / Lai, Chih-Cheng / Yu, Wen-Liang / Chao, Chien-Ming

2022 Volume 8, Issue 10

Abstract: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great threat to global health. In addition to SARS-CoV-2 itself, clinicians should be alert to the possible occurrence of co-infection or ... ...

Abstract	Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great threat to global health. In addition to SARS-CoV-2 itself, clinicians should be alert to the possible occurrence of co-infection or secondary infection among patients with COVID-19. The possible co-pathogens include bacteria, viruses, and fungi, but COVID-19-associated cryptococcosis is rarely reported. This review provided updated and comprehensive information about this rare clinical entity of COVID-19-associated cryptococcosis. Through an updated literature search till 23 August 2022, we identified a total of 18 culture-confirmed case reports with detailed information. Half (n = 9) of them were elderly. Fifteen (83.3%) of them had severe COVID-19 and ever received systemic corticosteroid. Disseminated infection with cryptococcemia was the most common type of cryptococcosis, followed by pulmonary and meningitis. Except one case of
Language	English
Publishing date	2022-10-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof8101111
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Article ; Online: SPINT2 mutations in the Kunitz domain 2 found in SCSD patients inactivate HAI-2 as prostasin inhibitor via abnormal protein folding and N-glycosylation.

Huang, Nanxi / Wang, Qiaochu / Bernard, Robert B / Chen, Chao-Yang / Hu, Je-Ming / Wang, Jehng-Kang / Chan, Khee-Siang / Johnson, Michael D / Lin, Chen-Yong

Human molecular genetics

2024 Volume 33, Issue 9, Page(s) 752–767

Abstract: Mutations in the Kunitz-type serine protease inhibitor HAI-2, encoded by SPINT2, are responsible for the pathogenesis of syndromic congenital sodium diarrhea (SCSD), an intractable secretory diarrhea of infancy. Some of the mutations cause defects in the ...

Abstract	Mutations in the Kunitz-type serine protease inhibitor HAI-2, encoded by SPINT2, are responsible for the pathogenesis of syndromic congenital sodium diarrhea (SCSD), an intractable secretory diarrhea of infancy. Some of the mutations cause defects in the functionally required Kunitz domain 1 and/or subcellular targeting signals. Almost all SCSD patients, however, harbor SPINT2 missense mutations that affect the functionally less important Kunitz domain 2. How theses single amino acid substitutions inactivate HAI-2 was, here, investigated by the doxycycline-inducible expression of three of these mutants in HAI-2-knockout Caco-2 human colorectal adenocarcinoma cells. Examining protein expressed from these HAI-2 mutants reveals that roughly 50% of the protein is synthesized as disulfide-linked oligomers that lose protease inhibitory activity due to the distortion of the Kunitz domains by disarrayed disulfide bonding. Although the remaining protein is synthesized as monomers, its glycosylation status suggests that the HAI-2 monomer remains in the immature, lightly glycosylated form, and is not converted to the heavily glycosylated mature form. Heavily glycosylated HAI-2 possesses full anti-protease activity and appropriate subcellular targeting signals, including the one embedded in the complex-type N-glycan. As predicted, these HAI-2 mutants cannot suppress the excessive prostasin proteolysis caused by HAI-2 deletion. The oligomerization and glycosylation defects have also been observed in a colorectal adenocarcinoma line that harbors one of these SPINT2 missense mutations. Our study reveals that the abnormal protein folding and N-glycosylation can cause widespread HAI-2 inactivation in SCSD patents.
MeSH term(s)	Humans ; Membrane Glycoproteins/metabolism ; Caco-2 Cells ; Glycosylation ; Mutation ; Diarrhea/congenital ; Protein Folding ; Adenocarcinoma ; Colorectal Neoplasms/genetics ; Disulfides ; Proteinase Inhibitory Proteins, Secretory/genetics ; Serine Endopeptidases
Chemical Substances	prostasin (EC 3.4.21.-) ; Membrane Glycoproteins ; Disulfides ; Proteinase Inhibitory Proteins, Secretory ; SPINT2 protein, human ; Serine Endopeptidases (EC 3.4.21.-)
Language	English
Publishing date	2024-01-23
Publishing country	England
Document type	Journal Article
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddae005
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Zs.A 3469: Show issues

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Article ; Online: Characteristics and outcomes for pulmonary aspergillosis in critically ill patients without influenza: A 3-year retrospective study.

Chao, Chien-Ming / Lai, Chih-Cheng / Chan, Khee-Siang / Yang, Chun-Chieh / Chen, Chin-Ming / Ho, Chung-Han / Ou, Hsuan-Fu / Yu, Wen-Liang

Journal of infection and public health

2023 Volume 16, Issue 12, Page(s) 2001–2009

Abstract: Background: Previous studies have revealed higher mortality rates in patients of severe influenza coinfected with invasive pulmonary aspergillosis (IPA) than in those without the coinfection; nonetheless, the clinical outcome of IPA in critically ill ... ...

Abstract	Background: Previous studies have revealed higher mortality rates in patients of severe influenza coinfected with invasive pulmonary aspergillosis (IPA) than in those without the coinfection; nonetheless, the clinical outcome of IPA in critically ill patients without influenza remains unclear. Patients and methods: This retrospective study was conducted in three institutes. From 2016-2018, all adult patients diagnosed with IPA in the intensive care units (ICUs) were identified. The logistic regression was used to identify the potential risk factors associated with in-hospital mortality in patients with non-influenza IPA. The stratified analysis of IPA patients with and without antifungal therapy was also performed. The final model was established using a forward approach, selecting variables with p-values less than 0.05. Results: Ninety patients were included during the study period, and 63 (70%) were men. The most common comorbidity was diabetes mellitus (n = 24, 27%), followed by solid cancers (n = 22, 24%). Antifungal therapy was administered to 50 (56%) patients, mostly voriconazole (n = 44). The in-hospital mortality rate was 49% (n = 44). Univariate analysis revealed that the risk factors for mortality included daily steroid dose, APACHE II score, SOFA score, C-reactive protein (CRP) level, carbapenem use, antifungal therapy, and caspofungin use. Multiple regression analysis identified four independent risk factors for mortality: age (Odds ratio [OR], 1.052, p = 0.013), daily steroid dose (OR, 1.057, p = 0.002), APACHE II score (OR, 1.094, p = 0.012), and CRP level (OR, 1.007, p = 0.008). Furthermore, the multivariable analysis identified that more physicians would initiate antifungal therapy for patients with prolonged steroid use (p = 0.001), lower white blood cell count (p = 0.021), and higher SOFA score (p = 0.048). Thus, under the selection bias, the independent risk factors for mortality in the antifungal treatment subgroup were daily steroid dose (OR, 1.046, p = 0.001) and CRP (OR, 1.006, p = 0.018), whereas the independent risk factor for mortality in the untreated group became APACHE II score (OR, 1.232, p = 0.007). Conclusions: Patients with IPA had a substantially high mortality. Overall, age, steroid use, APACHE II score, and CRP level were identified as the independent risk factors for mortality in patients in the ICU.
MeSH term(s)	Adult ; Male ; Humans ; Female ; Antifungal Agents/therapeutic use ; Influenza, Human/complications ; Influenza, Human/drug therapy ; Retrospective Studies ; Critical Illness ; Invasive Pulmonary Aspergillosis/drug therapy ; Intensive Care Units ; Steroids/therapeutic use
Chemical Substances	Antifungal Agents ; Steroids
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2467587-8
ISSN	1876-035X ; 1876-0341
ISSN (online)	1876-035X
ISSN	1876-0341
DOI	10.1016/j.jiph.2023.09.016
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Article ; Online: Risk factors for reintubation and mortality among patients who had unplanned extubation.

Chang, Ting-Chia / Cheng, Ai-Chin / Hsing, Shu-Chen / Chan, Khee-Siang / Chou, Willy / Chen, Chin-Ming

Nursing in critical care

2022 Volume 28, Issue 1, Page(s) 56–62

Abstract: Background: Unplanned extubation (UE) occurs among 2%-16% of patients with mechanical ventilation (MV). Failed UE requiring reintubation could be associated with several adverse events.: Aims: The aim of this study was to investigate the outcomes and ...

Abstract	Background: Unplanned extubation (UE) occurs among 2%-16% of patients with mechanical ventilation (MV). Failed UE requiring reintubation could be associated with several adverse events. Aims: The aim of this study was to investigate the outcomes and prognostic factors of patients with UE in intensive care units (ICUs). Methods: We prospectively registered the patients who had UE and retrospectively reviewed the electronic medical records for 96-bed ICUs between 1 January 2009, and 31 December 2020. Results: A total of 392 patients had UE, and 234 patients (59.7%) were ≥65 years (older adult group). The median Acute Physiology and Chronic Health Evaluation (APACHE) II score were 17 and the median Glasgow Coma Scale score was 10. In total, 205 patients (52.3%) were reintubated within 48 h (due to failed UE) and 75 patients (19.1%) died during hospitalization. Multivariate analyses were performed to evaluate those factors predicting failed UE and mortality. These analyses demonstrated that higher positive end-expiratory pressure (PEEP) and the admission APACHE II scores predicted failed UE. A higher fraction of inspiration O Conclusion: We concluded that among patients who had UE, higher FiO Relevance to clinical practice: Patients with high disease severity indices who have an increased risk of UE required special attention to techniques to prevent endotracheal tubes from accidental removal.
MeSH term(s)	Aged ; Humans ; Airway Extubation/adverse effects ; Intensive Care Units ; Intubation, Intratracheal ; Liver Cirrhosis/epidemiology ; Respiration, Artificial ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2022-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2011956-2
ISSN	1478-5153 ; 1362-1017
ISSN (online)	1478-5153
ISSN	1362-1017
DOI	10.1111/nicc.12777
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Zs.A 5204: Show issues

Location:
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Article ; Online: Epidemiological Correlation of Pulmonary

Liu, Jien-Wei / Ku, Yee-Huang / Chao, Chien-Ming / Ou, Hsuan-Fu / Ho, Chung-Han / Chan, Khee-Siang / Yu, Wen-Liang

Journal of fungi (Basel, Switzerland)

2021 Volume 7, Issue 3

Abstract: An increase in fungal spores in ambient air is reported during a spike in particulate matter ( ... ...

Abstract	An increase in fungal spores in ambient air is reported during a spike in particulate matter (PM
Language	English
Publishing date	2021-03-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof7030227
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Article ; Online: Collateral benefits on other respiratory infections during fighting COVID-19.

Chan, Khee-Siang / Liang, Fu-Wen / Tang, Hung-Jen / Toh, Han Siong / Yu, Wen-Liang

Medicina clinica (English ed.)

2020 Volume 155, Issue 6, Page(s) 249–253

Abstract: Purpose: Influenza virus infection is associated with a high disease burden. COVID-19 caused by SARS-CoV-2 has become a pandemic outbreak since January 2020. Taiwan has effectively contained COVID-19 community transmission. We aimed to validate whether ... ...

Abstract	Purpose: Influenza virus infection is associated with a high disease burden. COVID-19 caused by SARS-CoV-2 has become a pandemic outbreak since January 2020. Taiwan has effectively contained COVID-19 community transmission. We aimed to validate whether fighting COVID-19 could help to control other respiratory infections in Taiwan. Method: We collected week-case data of severe influenza, invasive Result: A downturn trend of severe influenza, invasive Conclusions: Fighting COVID-19 achieved collateral benefits on significant reductions of severe influenza burden, invasive
Keywords	covid19
Language	English
Publishing date	2020-09-30
Publishing country	Spain
Document type	Case Reports
ISSN	2387-0206
ISSN (online)	2387-0206
DOI	10.1016/j.medcle.2020.05.019
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Article ; Online: HAI-1 is required for the novel role of FGFBP1 in maintenance of cell morphology and F-actin rearrangement in human keratinocytes.

Lu, Dajun D / Huang, Nanxi / Li, Sheng-Wen A / Fang, Jessica R / Lai, Chih-Hsin / Wang, Jehng-Kang / Chan, Khee-Siang / Johnson, Michael D / Lin, Chen-Yong

Human cell

2023 Volume 36, Issue 4, Page(s) 1403–1415

Abstract: Formation and maintenance of skin barrier function require tightly controlled membrane-associated proteolysis, in which the integral membrane Kunitz-type serine protease inhibitor, HAI-1, functions as the primary inhibitor of the membrane-associated ... ...

Abstract	Formation and maintenance of skin barrier function require tightly controlled membrane-associated proteolysis, in which the integral membrane Kunitz-type serine protease inhibitor, HAI-1, functions as the primary inhibitor of the membrane-associated serine proteases, matriptase and prostasin. Previously, HAI-1 loss in HaCaT human keratinocytes resulted in an expected increase in prostasin proteolysis but a paradoxical decrease in matriptase proteolysis. The paradoxical decrease in shed active matriptase is further investigated in this study with an unexpected discovery of novel functions of fibroblast growth factor-binding protein 1 (FGFBP1), which acts as an extracellular ligand that can rapidly elicit F-actin rearrangement and subsequently affect the morphology of human keratinocytes. This novel growth factor-like function is in stark contrast to the canonical activity of this protein through interactions with FGFs for its pathophysiological functions. This discovery began with the observation that HAI-1 KO HaCaT cells lose the characteristic cobblestone morphology of the parental cells and exhibit aberrant F-actin formation along with altered subcellular targeting of matriptase and HAI-2. The alterations in cell morphology and F-actin status caused by targeted HAI-1 deletion can be restored by treatment with conditioned medium from parental HaCaT cells, in which FGFBP1 was identified by tandem mass spectrometry. Recombinant FGFBP1 down to 1 ng/ml was able to revert the changes caused by HAI-1 loss. Our study reveals a novel function of FGFBP1 in the maintenance of keratinocyte morphology, which depends on HAI-1.
MeSH term(s)	Humans ; Actins/metabolism ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Keratinocytes/metabolism ; Proteolysis ; Proteinase Inhibitory Proteins, Secretory/metabolism ; Intercellular Signaling Peptides and Proteins/metabolism
Chemical Substances	Actins ; Membrane Glycoproteins ; Proteinase Inhibitory Proteins, Secretory ; FGFBP1 protein, human (139946-12-6) ; Intercellular Signaling Peptides and Proteins
Language	English
Publishing date	2023-04-19
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1149134-6
ISSN	1749-0774 ; 0914-7470
ISSN (online)	1749-0774
ISSN	0914-7470
DOI	10.1007/s13577-023-00906-6
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Zs.A 3676: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Collateral benefits on other respiratory infections during fighting COVID-19.

Chan, Khee-Siang / Liang, Fu-Wen / Tang, Hung-Jen / Toh, Han Siong / Yu, Wen-Liang

Medicina clinica

2020 Volume 155, Issue 6, Page(s) 249–253

Abstract	Purpose: Influenza virus infection is associated with a high disease burden. COVID-19 caused by SARS-CoV-2 has become a pandemic outbreak since January 2020. Taiwan has effectively contained COVID-19 community transmission. We aimed to validate whether fighting COVID-19 could help to control other respiratory infections in Taiwan. Method: We collected week-case data of severe influenza, invasive Streptococcus pneumoniae disease and death toll from pneumonia among 25 calendar weeks of the influenza season for four years (2016-2020), which were reported to Taiwan CDC. Trend and slope differences between years were compared. Result: A downturn trend of severe influenza, invasive S. pneumoniae disease and the death toll from pneumonia per week in 2019/2020 season and significant trend difference in comparison to previous seasons were noted, especially after initiation of several disease prevention measures to fight potential COVID-19 outbreak in Taiwan. Conclusions: Fighting COVID-19 achieved collateral benefits on significant reductions of severe influenza burden, invasive S. pneumoniae disease activity, and the death toll from pneumonia reported to CDC in Taiwan.
MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/transmission ; Humans ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Influenza, Human/transmission ; Pandemics/prevention & control ; Pneumococcal Infections/epidemiology ; Pneumococcal Infections/prevention & control ; Pneumococcal Infections/transmission ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/prevention & control ; Pneumonia, Viral/transmission ; Retrospective Studies ; SARS-CoV-2 ; Taiwan/epidemiology
Keywords	covid19
Language	Spanish
Publishing date	2020-06-05
Publishing country	Spain
Document type	Journal Article
ZDB-ID	411607-0
ISSN	1578-8989 ; 0025-7753
ISSN (online)	1578-8989
ISSN	0025-7753
DOI	10.1016/j.medcli.2020.05.026
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Ua VI Zs.279: Show issues

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Article ; Online: The Impacts of Aspergillosis on Outcome, Burden and Risks for Mortality in Influenza Patients with Critical Illness.

Chao, Chien-Ming / Lai, Chih-Cheng / Ou, Hsuan-Fu / Ho, Chung-Han / Chan, Khee-Siang / Yang, Chun-Chieh / Chen, Chin-Ming / Yu, Wen-Liang

Journal of fungi (Basel, Switzerland)

2021 Volume 7, Issue 11

Abstract: Previous studies have revealed higher mortality rates in patients with severe influenza who are coinfected with invasive pulmonary aspergillosis (IPA) than in those without IPA coinfection; nonetheless, the clinical impact of IPA on economic burden and ... ...

Abstract	Previous studies have revealed higher mortality rates in patients with severe influenza who are coinfected with invasive pulmonary aspergillosis (IPA) than in those without IPA coinfection; nonetheless, the clinical impact of IPA on economic burden and risk factors for mortality in critically ill influenza patients remains undefined. The study was retrospectively conducted in three institutes. From 2016 through 2018, all adult patients with severe influenza admitted to an intensive care unit (ICU) were identified. All patients were classified as group 1, patients with concomitant severe influenza and IPA; group 2, severe influenza patients without IPA; and group 3, severe influenza patients without testing for IPA. Overall, there were 201 patients enrolled, including group 1 (
Language	English
Publishing date	2021-10-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof7110922
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Article ; Online: A mysterious surge of aspergillosis among non-SARS-CoV-2 patients during COVID-19 pandemic.

Lai, Chih-Cheng / Chen, Chin-Ming / Liao, Kuang-Ming / Chao, Chien-Ming / Chan, Khee-Siang / Yu, Wen-Liang

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi

2020 Volume 54, Issue 1, Page(s) 156–158

MeSH term(s)	COVID-19 ; Humans ; Pulmonary Aspergillosis/diagnosis ; Pulmonary Aspergillosis/epidemiology ; Taiwan/epidemiology
Language	English
Publishing date	2020-12-01
Publishing country	England
Document type	Letter
ZDB-ID	1497590-7
ISSN	1995-9133 ; 1684-1182 ; 0253-2662
ISSN (online)	1995-9133
ISSN	1684-1182 ; 0253-2662
DOI	10.1016/j.jmii.2020.11.002
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