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1.
Hum Mol Genet ; 33(9): 752-767, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38271183

RESUMEN

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.


Asunto(s)
Adenocarcinoma , Neoplasias Colorrectales , Serina Endopeptidasas , Humanos , Glicoproteínas de Membrana/metabolismo , Células CACO-2 , Glicosilación , Mutación , Diarrea/congénito , Pliegue de Proteína , Neoplasias Colorrectales/genética , Disulfuros , Proteínas Inhibidoras de Proteinasas Secretoras/genética
2.
Nurs Crit Care ; 28(1): 56-62, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35434930

RESUMEN

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 O2 (FiO2 ) and minute ventilation; lower haemoglobin (Hb); and higher instances of liver cirrhosis, cancer, and failed UE were independently associated with hospital mortality. CONCLUSION: We concluded that among patients who had UE, higher FiO2 or minute ventilation, or under MV or with lower Hb, liver cirrhosis, cancer, and failed UE tended to have higher mortality. 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.


Asunto(s)
Extubación Traqueal , Respiración Artificial , Anciano , Humanos , Extubación Traqueal/efectos adversos , Unidades de Cuidados Intensivos , Intubación Intratraqueal , Cirrosis Hepática/epidemiología , Estudios Retrospectivos , Factores de Riesgo
3.
Arch Phys Med Rehabil ; 98(5): 931-939, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-27979608

RESUMEN

OBJECTIVE: To evaluate the effects of a quality improvement program to introduce early mobilization on the outcomes of patients with mechanical ventilation (MV) in the intensive care unit (ICU). DESIGN: A retrospective observational study. SETTING: Nineteen-bed ICU at a medical center. PARTICIPANTS: Adults patients with MV (N=153) admitted to a medical ICU. INTERVENTIONS: A multidisciplinary team (critical care nurse, nursing assistant, respiratory therapist, physical therapist, patient's family) initiated the protocol within 72 hours of MV when patients become hemodynamically stable. We did early mobilization twice daily, 5d/wk during family visits (30min each time), and cooperated with family, if possible. MAIN OUTCOME MEASURES: MV duration, rate of successful weaning, and length of ICU and hospital stay. RESULTS: We enrolled 63 patients in the before protocol group and 90 in the after protocol group. The 2 groups were well matched in age, sex, body height, body weight, body mass index, disease severity, cause of intubation, number of comorbidities, and most underlying diseases. After protocol group patients had shorter MV durations (4.7d vs 7.5d; P<.001) and ICU stays (6.9d vs 9.9d; P=.001) than did before protocol group patients. Early mobilization was negatively associated with the duration of MV (ß=-.269; P<.002; 95% confidence interval [CI], -4.767 to -1.072), and the risk of MV for ≥7 days was lower in patients who underwent early mobilization (odds ratio, .082; 95% CI, .021-.311). CONCLUSIONS: The introduction of early mobilization for patients with MV in the ICU shortened MV durations and ICU stays. A multidisciplinary team that includes the patient's family can work together to improve the patient's clinical outcomes.


Asunto(s)
Ambulación Precoz/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Respiración Artificial/estadística & datos numéricos , Insuficiencia Respiratoria/rehabilitación , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Pesos y Medidas Corporales , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Desconexión del Ventilador/estadística & datos numéricos
4.
J Formos Med Assoc ; 116(9): 660-670, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28647219

RESUMEN

BACKGROUND/PURPOSE: Aspergillus-associated infection might comprise up to 23-29% of severe influenza patients from the community throughout stay in an intensive care unit (ICU). In Taiwan, cases of severe influenza with aspergillosis are increasingly reported. Therefore, we describe the relative risk of mortality among severe influenza patients with aspergillosis and other coinfections compared to severe influenza patients without Aspergillus coinfections. METHODS: We retrospectively reviewed 124 adult patients with severe influenza in a tertiary medical center in southern Taiwan from January 2015 through March 2016. The definition of probable aspergillosis required abnormal radiological findings and positive Aspergillus galactomannan (GM) antigen and/or Aspergillus isolation. RESULTS: Probable aspergillosis (detected throughout the whole course) and other coinfections (only community-acquired) were diagnosed in 21 (17%) and 38 (31%) of all patients respectively. Klebsiella pneumoniae (36.8%), Pseudomonas aeruginosa (31.6%) and Staphylococcus aureus (31.6%) were the most frequent isolates of other coinfections. In-ICU mortality of Aspergillus group (66.7%) was significantly higher than other coinfections (23.7%, p = 0.001) or control group without coinfections (15.4%, p < 0.001), with significant odds ratios after adjusting for important variables. The factor of GM index ≥0.6 had a 19.82 (95% CI, 4.91 to 80.07, p < 0.0001) odds of expiring in an ICU among the Aspergillus group. CONCLUSION: Dual Aspergillus and influenza infection is emerging in southern Taiwan. Meanwhile, community-acquired P. aeruginosa should be listed in the common copathogens with severe influenza. The 67% mortality linked to aspergillosis highlights the need for physicians to focus attention on patients with GM ≥ 0.6.


Asunto(s)
Aspergilosis/mortalidad , Coinfección/mortalidad , Gripe Humana/mortalidad , Anciano , Aspergilosis/diagnóstico por imagen , Coinfección/diagnóstico por imagen , Femenino , Mortalidad Hospitalaria , Humanos , Gripe Humana/diagnóstico por imagen , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
5.
Ann Plast Surg ; 74 Suppl 2: S75-9, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25664415

RESUMEN

BACKGROUND: The groin flap represents a milestone in the history of flap development, since it was the first successful free cutaneous flap. Once widely used, it is currently less popular owing to the variations in vascular anatomy and the small, short pedicle. To enhance the clinical applications of the groin flap, its merits need to be promoted and its faults improved, including making some useful innovations. METHODS: From February 2010 to February 2014, we successfully treated 35 patients with soft tissue defects in the extremities (28 patients), buttock (1 patient), and head (6 patients) using new designs in groin flaps: axial free (34 patients) or pedicle (1 patient) groin flaps. RESULTS: All types of axial groin flaps survived successfully in the 2 to 38 months' (mean, 15.6 months) follow-up. The branches of the superficial circumflex iliac artery used for the axial flap design were 2 to 4 (mean, 3.09). The flap size ranged from 1×1.5 cm to 11×30 cm. No significant complications developed in any of the patients, with the exception of 2 mildly bulky flaps. CONCLUSIONS: This axial design of freestyle groin flaps not only preserves the earlier merits of the groin flap but also creates many new advantages: (1) reliability is greater, (2) ability to tailor the dimensions and flap paddles to the lesions, (3) options available to "lengthen" flap pedicles, and (4) local anesthesia usable with free flaps for reconstruction.


Asunto(s)
Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos , Adulto , Anciano , Femenino , Ingle/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
6.
Nephrology (Carlton) ; 19(3): 136-42, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24330098

RESUMEN

AIM: Visceral fat is more significantly correlated with inflammation markers and oxidative stress than is subcutaneous fat. Myeloperoxidase is one inflammatory signal secreted after polymorphonuclear leukocytes are stimulated. However, few studies discuss the correlation between visceral fat and the inflammatory response in patients with chronic kidney disease (CKD). METHODS: Sixty-six patients with CKD were enrolled and 60 healthy participants. Visceral fat levels were obtained using bioelectrical impedance analysis. Traditional risk factors for myeloperoxidase were analyzed. RESULTS: Baseline myeloperoxidase levels were significantly different between patients and controls, and were correlated with visceral fat after they had been adjusted for residual renal function. A multivariate linear regression model revealed that the neutrophil count and visceral fat and serum albumin levels were significant predictors of plasma myeloperoxidase in patients with CKD, but not in controls. The neutrophil count was correlated with myeloperoxidase only in the CKD group. CONCLUSION: Visceral fat predicted plasma myeloperoxidase in patients with CKD, but not in healthy controls. Myeloperoxidase was probably contributed by primed and activated neutrophils that had been irritated by visceral fat in patients with CKD.


Asunto(s)
Grasa Intraabdominal/fisiología , Peroxidasa/fisiología , Insuficiencia Renal Crónica/enzimología , Anciano , Proteína C-Reactiva/análisis , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peroxidasa/sangre , Insuficiencia Renal Crónica/sangre
7.
Am J Emerg Med ; 32(3): 289.e1-2, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24176592

RESUMEN

Vibrio vulnificus typically causes septicemia and necrotic wound infection. Among V vulnificus­related complications, acute nonthrombotic myocardial damage has not been reported. The most effective antibiotic treatment of V vulnificus infection includes combination of a third-generation cephalosporin and a tetracycline or its analogue. However, recommendations of a fourth-generation cephalosporinbased regimen for treating the disease are not established. A 67-year-old diabetic man acquired V vulnificus infection via a fish-stunning wound on the right foot. The patients developed septicemia and hemorrhagic bullous necrotic wounds and followed by acute nonthrombotic cardiac injury with low cardiac output. After initial resuscitation, we applied dobutamine inotropic therapy with combination of cefpirome and ciprofloxacin or minocycline, which achieved a good clinical outcome.


Asunto(s)
Cardiomiopatías/diagnóstico , Sepsis/diagnóstico , Vibriosis/diagnóstico , Infección de Heridas/diagnóstico , Enfermedad Aguda , Anciano , Cardiomiopatías/etiología , Humanos , Masculino , Sepsis/etiología , Vibriosis/complicaciones , Infección de Heridas/complicaciones
8.
Am J Emerg Med ; 31(7): 1037-41, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23702054

RESUMEN

OBJECTIVES: Vibrio vulnificus causes potentially life-threatening and rapidly progressing infections. Therefore, the severity-of-illness assessment appears to be important for V vulnificus-infected patients at the time of admission. The aim of our study was to evaluate the performance of the severity-of-illness scoring model on admission in V vulnificus-infected patients. METHODS: One hundred seventy-one consecutive patients (mean age: 63.1 ± 12.3 years) with V vulnificus infection who were admitted to a teaching hospital between January 1999 and June 2010 were included in the study. Demographic and clinical characteristics, illness severity on admission, treatment, and outcomes were collected for each patient and extracted for analysis. Logistic regression and receiver operating characteristic curve analyses were performed. RESULTS: The mean Rapid Emergency Medicine Score (REMS) on admission was 6.5 ± 3.0 points. During hospitalization, 68 patients (40%) required intensive care. The overall case-fatality rate was 25%. In multivariate analysis, the presence of underlying liver disease (P = .002), hemorrhagic bullous lesions/necrotizing fasciitis (P = .012), and higher REMS values on admission (P < .0001) were associated with increased mortality risk; a time span <24 hours between arrival and surgical treatment was associated with a decreased mortality risk (P = .007). Additionally, the area under the receiver operating characteristic (ROC) curve for the REMS in predicting mortality risk was 0.895 (P < .0001). An optimal cut-off REMS ≥8 had a sensitivity of 81% and a specificity of 85%, with a 26.6-fold mortality risk (P < .0001) and a 12.5-fold intensive care unit admission risk (P < .0001). CONCLUSION: The REMS could provide clinicians with an effective adjunct risk stratification tool for V vulnificus-infected patients.


Asunto(s)
Técnicas de Apoyo para la Decisión , Índice de Severidad de la Enfermedad , Vibriosis/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Mortalidad Hospitalaria , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Curva ROC , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad , Resultado del Tratamiento , Vibriosis/terapia
9.
J Infect Public Health ; 16(12): 2001-2009, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37890223

RESUMEN

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.


Asunto(s)
Gripe Humana , Aspergilosis Pulmonar Invasiva , Adulto , Masculino , Humanos , Femenino , Antifúngicos/uso terapéutico , Gripe Humana/complicaciones , Gripe Humana/tratamiento farmacológico , Estudios Retrospectivos , Enfermedad Crítica , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Unidades de Cuidados Intensivos , Esteroides/uso terapéutico
10.
Hum Cell ; 36(4): 1403-1415, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37076641

RESUMEN

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.


Asunto(s)
Actinas , Glicoproteínas de Membrana , Humanos , Actinas/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Queratinocitos/metabolismo , Proteolisis , Proteínas Inhibidoras de Proteinasas Secretoras/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo
11.
J Antimicrob Chemother ; 67(2): 488-93, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22117030

RESUMEN

OBJECTIVES: To compare the effectiveness of a third-generation cephalosporin alone, a third-generation cephalosporin plus minocycline, and a fluoroquinolone in patients with necrotizing fasciitis (NF) caused by Vibrio vulnificus. METHODS: A retrospective review of case notes was performed for 89 patients who presented with NF caused by V. vulnificus and underwent surgical intervention within 24 h of admission between 2003 and 2010. Data on comorbidities, clinical manifestations, laboratory studies, treatments and outcomes were extracted for analysis. These patients were grouped according to the antimicrobials prescribed: those who received only a third-generation cephalosporin (Group 1; n = 18); a third-generation cephalosporin plus minocycline (Group 2; n = 49); or a fluoroquinolone with/without minocycline (Group 3; n = 22). RESULTS: The mean age of the 89 patients included in the study was 64.0 ± 12.0 years (range 33-89 years); 55% of the patients were male. There were no differences in age, sex or clinical characteristics among the three groups except that patients in Group 3 had a higher frequency of underlying chronic renal insufficiency than those in Groups 1 and 2 (P = 0.009). Groups 2 and 3 each had a significantly lower case fatality rate than Group 1 (61% in Group 1 versus 14% in Group 2, P = 0.0003; 61% in Group 1 versus 14% in Group 3, P = 0.0027), while no difference in case fatality rate was noted between Groups 2 and 3. CONCLUSIONS: Our data suggested that, in addition to primary surgery, fluoroquinolones or third-generation cephalosporins plus minocycline are the best option for antibiotic treatment of NF caused by V. vulnificus.


Asunto(s)
Antibacterianos/administración & dosificación , Fascitis Necrotizante/tratamiento farmacológico , Fascitis Necrotizante/microbiología , Vibriosis/tratamiento farmacológico , Vibriosis/microbiología , Vibrio vulnificus/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Cefalosporinas/administración & dosificación , Quimioterapia Combinada/métodos , Fascitis Necrotizante/cirugía , Femenino , Fluoroquinolonas/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Minociclina/administración & dosificación , Resultado del Tratamiento , Vibriosis/cirugía
13.
J Fungi (Basel) ; 8(10)2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36294675

RESUMEN

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 C. laurentii, all other cases are by C. neoformans. Liposomal amphotericin B and fluconazole were the most commonly used antifungal agents. The overall mortality was 61.1% (11/18) and four of them did not receive antifungal agents before death. Improving the poor outcome requires a physician's high suspicion, early diagnosis, and prompt treatment.

14.
Genes Dis ; 9(4): 1049-1061, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35685459

RESUMEN

The integral membrane, Kunitz-type serine protease inhibitors HAI-1 and HAI-2, can suppress the proteolytic activity of the type 2 transmembrane serine protease matriptase with high specificity and potency. High levels of extracellular matriptase proteolytic activity have, however, been observed in some neoplastic B-cells with high levels of endogenous HAI-2, indicating that HAI-2 may be an ineffective matriptase inhibitor at the cellular level. The different effectiveness of the HAIs in the control of extracellular matriptase proteolytic activity is examined here. Upon inducing matriptase zymogen activation in the HAI Teton Daudi Burkitt lymphoma cells, which naturally express matriptase with very low levels of HAI-2 and no HAI-1, nascent active matriptase was rapidly inhibited or shed as an enzymatically active enzyme. With increasing HAI-1 expression, cellular matriptase-HAI-1 complex increased, and extracellular active matriptase decreased proportionally. Increasing HAI-2 expression, however, resulted in cellular matriptase-HAI-2 complex levels reaching a plateau, while extracellular active matriptase remained high. In contrast to this differential effect, both HAI-1 and HAI-2, even at very low levels, were shown to promote the expression and cell-surface translocation of endogenous matriptase. The difference in the suppression of extracellular active matriptase by the two closely related serine protease inhibitors could result from the primarily cell surface expression of HAI-1 compared to the mainly intracellular localization of HAI-2. The HAIs, therefore, resemble one another with respect to promoting matriptase expression and surface translocation but differ in their effectiveness in the control of extracellular matriptase enzymatic activity.

15.
J Fungi (Basel) ; 7(3)2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33808688

RESUMEN

An increase in fungal spores in ambient air is reported during a spike in particulate matter (PM2.5 and PM10) aerosols generated during dust or smog events. However, little is known about the impact of ambient bioaerosols on fungal infections in humans. To identify the correlation between the incidence of pulmonary aspergillosis and PM-associated bioaerosols (PM2.5 and PM10), we retrospectively analyzed data between 2015 and 2018 (first stage) and prospectively analyzed data in 2019 (second stage). Patient data were collected from patients in three medical institutions in Tainan, a city with a population of 1.88 million, located in southern Taiwan. PM data were obtained from the Taiwan Air Quality Monitoring Network. Overall, 544 non-repeated aspergillosis patients (first stage, n = 340; second stage, n = 204) were identified and enrolled for analysis. The trend of aspergillosis significantly increased from 2015 to 2019. Influenza A (H1N1) and ambient PMs (PM2.5 and PM10) levels had significant effects on aspergillosis from 2015 to 2018. However, ambient PMs and influenza A (H1N1) in Tainan were correlated with the occurrence of aspergillosis in 2018 and 2019, respectively. Overall (2015-2019), aspergillosis was significantly correlated with influenza (p = 0.002), influenza A (H1N1) (p < 0.001), and PM2.5 (p = 0.040) in Tainan City. Using a stepwise regression model, influenza A (H1N1) (p < 0.0001) and Tainan PM10 (p = 0.016) could significantly predict the occurrence of aspergillosis in Tainan. PM-related bioaerosols and influenza A (H1N1) contribute to the incidence of pulmonary aspergillosis.

16.
J Fungi (Basel) ; 7(11)2021 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-34829211

RESUMEN

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 (n = 40), group 2 (n = 50), and group 3 (n = 111). Group 1 patients had a significantly higher mortality rate (20/40, 50%) than that of group 2 (6/50, 12%) and group 3 (18/11, 16.2%), p < 0.001. The risk factors for IPA occurrence were solid cancer and prolonged corticosteroid use in ICU of >5 days. Group 1 patients had significantly longer hospital stay and higher medical expenditure than the other two groups. The risk factors for mortality in group 1 patients included patients' Charlson comorbidity index, presenting APACHE II score, and complication of severe acute respiratory distress syndrome. Overall, IPA has a significant adverse impact on the outcome and economic burden of severe influenza patients, who should be promptly managed based on risk host factors for IPA occurrence and mortality risk factors for coinfection with both diseases.

17.
Crit Care Med ; 38(10): 1984-90, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20657269

RESUMEN

OBJECTIVE: Vibrio vulnificus infection is uncommon but potentially life-threatening. The aim of this study was to evaluate clinical outcomes and prognostic factors for patients with V. vulnificus infections admitted to an intensive care unit. DESIGN: Retrospective study. SETTING: Multidisciplinary intensive care unit in a 2300-bed teaching hospital. PATIENTS: Eighty-five adult patients (≥ 18 yrs) with V. vulnificus infections who required intensive care were enrolled and reviewed during a 10-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-four of the 85 patients died, giving an intensive care unit mortality rate of 40%. The mean Acute Physiology and Chronic Health Evaluation II score on intensive care unit admission was 18.4 (95% confidence interval, 17.1-19.8). The most common underlying disease was hepatic disease (48%) followed by diabetes mellitus (22%). Multivariate analysis showed that risk factors for intensive care unit mortality were the presence of hemorrhagic bullous skin lesions/necrotizing fasciitis (relative risk, 2.4; 95% confidence interval, 1.3-4.5; p = .006), skin/soft tissue infections involving two or more limbs (relative risk, 2.5; 95% confidence interval, 1.1-5.7; p = .025), and higher Acute Physiology and Chronic Health Evaluation II scores on intensive care unit admission (relative risk, 1.2; 95% confidence interval, 1.1-1.3; p = .0001). In contrast, surgical treatment < 24 hrs after arrival was inversely associated with intensive care unit mortality (relative risk, 0.35; 95% confidence interval, 0.15-0.79; p = .012). In addition, the area under the receiver operating characteristic curve for Acute Physiology and Chronic Health Evaluation II for predicting intensive care unit mortality was 0.945 (95% confidence interval, 0.873-0.983; p = .0001). An optimal cutoff Acute Physiology and Chronic Health Evaluation II score of ≥ 20 had a sensitivity of 97% and a specificity of 86% with a 41.4-fold increased risk of fatality (p = .0003). CONCLUSIONS: This study found that V. vulnificus-infected patients with hemorrhagic bullous skin lesions/necrotizing fasciitis, skin/soft tissue infections involving two or more limbs, or higher Acute Physiology and Chronic Health Evaluation II scores have high risks of intensive care unit mortality. However, patients receiving prompt surgical treatments within 24 hrs after admission have better prognoses.


Asunto(s)
Cuidados Críticos , Vibriosis/diagnóstico , Vibrio vulnificus , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Terapia Combinada , Intervalos de Confianza , Cuidados Críticos/estadística & datos numéricos , Fascitis Necrotizante/etiología , Fascitis Necrotizante/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Curva ROC , Estudios Retrospectivos , Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Vibriosis/complicaciones , Vibriosis/mortalidad , Vibriosis/terapia
18.
Med Clin (Engl Ed) ; 155(6): 249-253, 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-33020740

RESUMEN

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.


PROPÓSITOS: La COVID-19, causada por SARS-CoV-2, se ha convertido en un brote de pandemia desde enero de 2020. Taiwán ha contenido efectivamente la transmisión comunitaria de la COVID-19. Por otra parte, la influenza también es una enfermedad que se asocia con una alta carga de morbilidades. El objetivo del estudio es validar si combatir la COVID-19 podría ayudar a controlar otras infecciones respiratorias en Taiwán. MÉTODOS: Recopilamos datos semanales de casos de influenza grave, infecciones invasivas por Streptococcus pneumoniae y número de muertes por neumonía, que se informaron a los CDC de Taiwán en las 25 semanas de la temporada de influenza durante 4 años (2016-2020). Comparamos las diferencias de tendencia y de pendiente entre los años. RESULTADOS: Se observó una tendencia a la baja de la influenza grave, de las infecciones invasivas por Streptococcus pneumoniae y del número de muertes por neumonía por semana en la temporada de influenza de 2019-2020. Se observaron diferencias significativas en la tendencia en comparación con las temporadas anteriores, especialmente después del inicio de varias medidas de prevención de enfermedades para combatir el posible brote de COVID-19 en Taiwán. CONCLUSIONES: Por el número de casos reportados a los CDC de Taiwán, encontramos que la lucha contra la COVID-19 logró beneficios colaterales en cuanto a reducción significativa de la carga de la influenza grave, a las infecciones invasivas por Streptococcus pneumoniae y al número de muertes por neumonía.

19.
Med Clin (Barc) ; 155(6): 249-253, 2020 09 25.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32586667

RESUMEN

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.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/prevención & control , Gripe Humana/prevención & control , Pandemias/prevención & control , Infecciones Neumocócicas/prevención & control , Neumonía Viral/prevención & control , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Humanos , Gripe Humana/epidemiología , Gripe Humana/transmisión , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/transmisión , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Estudios Retrospectivos , SARS-CoV-2 , Taiwán/epidemiología
20.
Sci Rep ; 10(1): 4980, 2020 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-32188892

RESUMEN

Acute respiratory failure requiring mechanical ventilation is a major indicator of intensive care unit (ICU) admissions in cirrhotic patients and is an independent risk factor for ICU mortality. This retrospective study aimed to investigate the outcome and mortality risk factors in patients with liver cirrhosis (LC) who required prolonged mechanical ventilation (PMV) between 2006 and 2013 from two databases: Taiwan's National Health Insurance Research Database (NHIRD) and a hospital database. The hospital database yielded 58 LC patients (mean age: 65.3 years; men: 65.5%). The in-hospital mortality was significantly higher than in patients without LC. Based on the NHIRD database of PMV cases, patients were age-gender matched in a ratio of 1:2 for patients with and without LC. Model for End-Stage Liver Disease (MELD) score was calculated. The mortality was higher in patients with LC (19.5%) than those without LC (18.12%), though not statistically significant (p = 0.0622). Based on the hospital database, risk factor analysis revealed that patients who died had significant higher MELD score than the survivors (18.9 vs 13.7, p = 0.036) and patients with MELD score of >23 had higher risk of mortality than patients with MELD score of ≤23 (adjusted OR:9.26, 95% CI: 1.96-43.8). In conclusion, the in-hospital mortality of patients with high MELD scores who required PMV was high. MELD scores may be useful predictors of mortality in these patients.


Asunto(s)
Mortalidad Hospitalaria/tendencias , Hospitalización/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Cirrosis Hepática/mortalidad , Respiración Artificial/mortalidad , Índice de Severidad de la Enfermedad , Anciano , Femenino , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/terapia , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Taiwán/epidemiología
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