SPINT2 mutations in the Kunitz domain 2 found in SCSD patients inactivate HAI-2 as prostasin inhibitor via abnormal protein folding and N-glycosylation.

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.

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

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.

HAI-1 is required for the novel role of FGFBP1 in maintenance of cell morphology and F-actin rearrangement in human keratinocytes.

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.

Risk factors for reintubation and mortality among patients who had unplanned extubation.

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.

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

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.

Differential subcellular distribution renders HAI-2 a less effective protease inhibitor than HAI-1 in the control of extracellular matriptase proteolytic activity.

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.

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

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.

Epidemiological Correlation of Pulmonary Aspergillus Infections with Ambient Pollutions and Influenza A (H1N1) in Southern Taiwan.

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.

Collateral benefits on other respiratory infections during fighting COVID-19.

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.

Collateral benefits on other respiratory infections during fighting COVID-19 / Beneficios colaterales en otras infecciones respiratorias durante la lucha contra la COVID-19

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

Collateral benefits on other respiratory infections during fighting COVID-19.

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.

Outcome of liver cirrhosis patients requiring prolonged mechanical ventilation.

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.

Prognosis of patients with acute respiratory failure and prolonged intensive care unit stay.

BACKGROUND: Reasons for the prolonged critical care support include uncertainty of outcome, the complex dynamic created between physicians with care team members and the patient's family over a general unwillingness to surrender to unfavorable outcomes. The purpose of this study was to investigate outcomes and identify risk factors of patients with acute respiratory failure (ARF) who required a prolonged intensive care unit (ICU) stay (≥21 days). It may provide reference to screen patients who are suitable for hospice care. METHODS: The medical records of all ARF patients with a prolonged ICU stay were retrospectively reviewed. The primary outcome was in-hospital mortality. RESULTS: We identified 1,189 patients. Sepsis (n=896, 75.4%) was the most common cause of prolonged ICU stays, following by renal failure (n=232, 19.5%), and unstable hemodynamic status vasopressors or arrhythmia (n=208, 17.5%). Using multivariable logistic regression, we identified eight risk factors of death: age >75 years, ICU stay for more than 28 days, APACHE II score ≥25, unstable hemodynamic status, renal failure, hepatic failure, massive gastrointestinal tract bleeding, and using a fraction of inspired oxygen (FiO2) ≥40%. The overall in-hospital mortality rate was 53.6% (n=637), and it up to 75.3% (216/287) for patients with at least three risk factors. CONCLUSIONS: The outcome of patients with ARF who required prolonged ICU stay was poor. They had a high risk of in-hospital mortality. Palliative care should be considered as a reasonable option for the patients at high risk of death.

High-level ambient particulate matter before influenza attack with increased incidence of Aspergillus antigenemia in Southern Taiwan, 2016.

We found significant correlation between the incidence of severe influenza and Aspergillus antigenemia among medical intensive care unit patients for 7-month observation (coefficient γ=0.976, p<0.001). High-level ambient pollution was noticed for 2 months before the epidemic, highlighting that influenza patients might coinfect with aspergillosis in the community.

Outcomes of patients with severe influenza infection admitted to intensive care units: a retrospective study in a medical centre.

PURPOSE: This study assessed clinical manifestations and prognostic factors of critically ill patients with severe influenza admitted to the intensive care unit (ICU) in Taiwan's recent outbreak. METHODOLOGY: Patients admitted to ICU for severe influenza between January 1, 2015, and March 31, 2016, were identified and their medical records were retrospectively reviewed. The primary endpoints were outcomes and predictors of in-hospital mortality. RESULTS: There were 125 patients with an average Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 20.8. Hypertension (62.4 %) and diabetes mellitus (40.8 %) were the two most common underlying diseases. Ninety-eight (78.4 %) patients had at least one organ failure: the lungs were the most common (71.2 %), followed by the heart (53.6 %). Two of the most common symptoms of patients at ICU admission were fever (68.0 %) and cough (78.4 %). Thirty-three patients (26.4 %) died; most (40.9 %) were middle-aged (50-65 years old). A Cox regression analysis showed that multiple organ failure (MOF) [hazard ratio (HR)=3.618; 95 % CI=1.058-13.662] was significantly associated with higher risk of death. In contrast, a fluid-negative balance within 7 days of admission (HR=0.362; 95 % CI=0.140-0.934) was significantly associated with a lower risk of death. CONCLUSION: The mortality rate of severe influenza patients admitted to the ICU was high, especially in middle-aged adults. The risk of mortality was associated with ≥2 organ failures. A negative fluid balance predicts survival.

Prognostic factors and outcomes of unplanned extubation.

This study investigated the prognostic factors and outcomes of unplanned extubation (UE) in patients in a medical center's 6 intensive care units (ICUs) and calculated their mortality risk. We retrospectively reviewed the medical records of all adult patients in Chi Mei Medical Center who underwent UE between 2009 and 2015. During the study period, there were 305 episodes of UE in 295 ICU patients (men: 199 [67.5%]; mean age: 65.7 years; age range: 18-94 years). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 16.4, mean therapeutic intervention scoring system (TISS) score was 26.5, and mean Glasgow coma scale score was 10.4. One hundred thirty-six patients (46.1%) were re-intubated within 48 h. Forty-five died (mortality rate: 15.3%). Multivariate analyses showed 5 risk factors-respiratory rate, APACHE II score, uremia, liver cirrhosis, and weaning status-were independently associated with mortality. In conclusion, five risk factors including a high respiratory rate before UE, high APACHE II score, uremia, liver cirrhosis, and not in the process of being weaned-were associated with high mortality in patients who underwent UE.

Multidisciplinary interventions and continuous quality improvement to reduce unplanned extubation in adult intensive care units: A 15-year experience.

We conduct a retrospective study of patients with unplanned extubation (UE) in adult intensive care units (ICU) at a medical center. In 2001, a multidisciplinary team of intensivists, senior residents, nurses, and respiratory therapists was established at Chi Mei Medical Center. The improvement interventions, implemented between 2001 and 2015, were organized around 8 key areas: standardizing procedures, improving communication skills, revising sedation and weaning protocols, changing strategies for restraints, establishing a task force for identifying and managing high-risk patients, using new quality-improvement models as breakthrough series and team resource management, using the strategy of accountability without assigning blame, and changing a new method to secure endotracheal tube. We measured the outcome as the annual event and the rate of UE. During this 15-year period, there were 1404 episodes of UE, with 44,015 episodes of mechanical ventilation (MV) (319,158 ventilator-days). The overall rate of UE was 3.19/100 ventilated patients (4.40/1000 ventilator-days). In 2001, there were 188 episodes of UE and the rate of UE was 6.82/100 ventilated patients or 9.0/1000 ventilator-days. After this continue quality improvement project had been implemented, the annual number of episodes of UE declined to 27, and the rate fell to 0.95/100 ventilated patients or 1.36/1000 ventilator-days in 2015. Overall, the trend analysis showed the change was significant with P < .0001. In conclusion, UE in adult ICU can be continuously and effectively reduced using multidisciplinary and sequential quality improvement interventions.

Higher mortality of severe influenza patients with probable aspergillosis than those with and without other coinfections.

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.