Bronchoalveolar lavage fluid analysis and mortality risk in systemic lupus erythematosus patients with pneumonia and respiratory failure

BackgroundOur aim was to characterize etiologic diagnoses obtained from bronchoalveolar lavage fluid (BALF) and blood specimens, and to identify risk factors for mortality in systemic lupus erythematosus (SLE) patients with pneumonia and respiratory failure.MethodsWe conducted a retrospective analysis of SLE patients with pneumonia and respiratory failure. Clinical characteristics, laboratory profiles, and microbiology in BALF and blood samples were evaluated. We performed univariable analyses to identify mortality risk factors.ResultsAll 24 patients (F:M = 21:3, median age 46.5 years; disease duration 11 years) received mechanical ventilation (median duration: 11 days). Pathogens identified in BALF included Pneumocystis jiroveci (12 patients [50%]), cytomegalovirus (CMV, 7 patients [29.2%]), and bacteria (11 patients [45.8%]). Thirteen patients (54.2%) yielded pathogens in blood (CMV in 8 patients [33.3%] and Escherichia coli in 5 patients [20.8%]). Eight developed septic shock, and 9 died within 30 days. Univariable analysis identified thrombocytopenia (odds ratio [OR]: 8.0, 95% confidence interval [CI]: 1.23–52.25), bacteremia within 30 days before or after endotracheal intubation (OR: 8.0, 95% CI: 1.23–52.5), and P. jiroveci pneumonia (PJP, OR: 7.0, 95% CI: 1.04–46.95) as risk factors for 30-day mortality. Kaplan–Meier analysis confirmed an increased risk of 30-day mortality with thrombocytopenia and bacteremia.ConclusionThere are high prevalence rates of PJP and CMV infections as evidenced by BALF analyses in SLE patients with pneumonia and respiratory failure. BALF analysis can facilitate rescue therapy per pathogen. Thrombocytopenia, bacteremia, and PJP in SLE patients can increase their 30-day mortality, so warrant early and aggressive treatments.     

Human herpes virus co-infection is associated with mortality in HIV-negative patients with Pneumocystis jirovecii pneumonia

The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori–Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6?±?18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9?±?20.4. Underlying conditions included hematologic malignancies (n?=?21), vasculitis (n?=?13), and solid tumors (n?=?13). Most patients were receiving systemic corticosteroids (n?=?63) and cytotoxic drugs (n?=?51). Not a single patient received trimethoprim–sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p?=?0.0131), ARDS (p?<?0.0001), shock (p?<?0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p?=?0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5–121.9], p?<?0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.     

Diagnostic accuracy of serum (1-3)-β-D-glucan for Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis

BackgroundPneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring semi-invasive respiratory sampling. The serum 1,3-β-D-glucan (BDG) assay has been proposed as a minimally invasive test for the presumptive diagnosis of PJP.MethodWe carried out a systematic review and meta-analysis using articles in the English language published between January 1960 and September 2019. We estimated the pooled sensitivity and specificity of BDG testing using a bivariate random effects approach and compared test performance in human immunodeficiency virus (HIV) and non-HIV subgroups with meta-regression. Data from the pooled sensitivity and specificity were transformed to generate pre- and post-test probability curves.ResultsTwenty-three studies were included. The pooled sensitivity and specificity of serum BDG testing for PJP were 91% (95%CI 87–94%) and 79% (95%CI 72–84%) respectively. The sensitivity in patients with HIV was better than in patients without (94%, 95%CI 91–96%) versus 86% (95%CI 78–91%) (p 0.02), with comparable specificity (83%, 95%CI 69–92% versus 83%, 95%CI 72–90%) (p 0.10). A negative BDG was only associated with a low post-test probability of PJP (≤5%) when the pre-test probability was low to intermediate (≤20% in non-HIV and ≤50% in HIV).ConclusionsAmong patients with a higher likelihood of PJP, the pooled sensitivity of BDG is insufficient to exclude infection. Similarly, for most cases, the pooled specificity is inadequate to diagnose PJP. Understanding the performance of BDG in the population being investigated is therefore essential to optimal clinical decision-making.     

Do Intensive Care Unit treatment modalities predict mortality in geriatric patients: An observational study from an Indian Intensive Care Unit

Background:Ageing being a global phenomenon, increasing number of elderly patients are admitted to Intensive Care Units (ICU). Hence, there is a need for continued research on outcomes of ICU treatment in the elderly.Objectives:Examine age-related difference in outcomes of geriatric ICU patients. Analyze ICU treatment modalities predicting mortality in patients >65 years of age.Results:The observed overall ICU mortality rate in the study population was 19.6%; no statistical difference was observed between the control and geriatric age group in overall mortality (P > 0.05). Mechanical ventilation (P = 0.003, odds ratio [OR] =0.573, 95% confidence interval [CI] =0.390–0.843) and use of inotropes (P = 0.018, OR = 0.661, 95% CI = 0.456–0.958) were found to be predictors of mortality in elderly population. On multivariate analysis, inotropic support was found to be an independent ICU treatment modality predicting mortality in the geriatric age group (β coefficient = 1.221, P = 0.000).Conclusion:Intensive Care Unit mortality rates increased in the geriatric population requiring mechanical ventilation and inotropes during ICU stay. Only inotropic support could be identified as independent risk factor for mortality.     

Efficacy and Tolerance of HCV Treatment in HIV-HCV Coinfected Patients: The Potential Interaction of PI Treatment

Abstract

Purpose: To evaluate tolerance and efficacy of an open-label interferon-ribavirin treatment and their determinants in 62 HCV-HIV coinfected patients in routine followup. Method: Patients received at least 6 and up to 12 months of combination interferon alpha-2b (peg or not) plus ribavirin. Determinants of therapeutic success were estimated by a multivariate logistic regression. Results: Five patients stopped the study, 4 were lost to follow-up, and 53 participated in the entire therapeutic protocol. Among these 53, the end-of-treatment results showed complete clearance of HCV-RNA in 17 (32%). A sustained virologic response (SVR) after 6 or 9 months was observed in 9 (17%) patients, 3 relapsed, and data were not available for 5. Genotype 3a (odds ratio [OR] = 14.4; confidence interval [CI] = 1.84-110.3) favored SVR and treatment with protease inhibitor (PI) therapeutic resistance (OR = 14.4; CI = 1.01-200); as well, a higher fibrosis score tended to increase resistance (p = .11). Adverse events were reported by 24/53 patients (45.3%). Conclusion: HCV therapy associating interferon and ribavirin in HCV-HIV coinfected patients is well accepted even if tolerance is moderate. Treatment permitted SVR in at least 17% of the cases. This is likely when patients initiate treatment at the early fibrosis stage and are infected with genotype 3a. The potential interaction with PI therapy should be explored.     

Predictors for treatment outcomes among patients with drug-susceptible tuberculosis in the Netherlands: a retrospective cohort study

ObjectivesWe evaluated treatment outcomes and predictors for poor treatment outcomes for tuberculosis (TB) among native- and foreign-born patients with drug-susceptible TB (DSTB) in the Netherlands.MethodsThis retrospective cohort study included adult patients with DSTB treated from 2005 to 2015 from a nationwide exhaustive registry. Predictors for unsuccessful treatment outcomes (default and failure) and TB-associated mortality were analysed using multivariate logistic regression.ResultsAmong 5674 identified cases, the cumulative incidence of unsuccessful treatment and mortality were 2.6% (n/N = 146/5674) and 2.0% (112/5674), respectively. Although most patients were foreign-born (71%; 4042/5674), no significant differences in these outcomes were observed between native- and foreign-born patients (p > 0.05). Significant predictors for unsuccessful treatment were aged 18–24 years (odds ratio (OR), 2.04; 95% CI 1.34–3.10), homelessness (OR, 2.56; 95% CI 1.16–5.63), prisoner status (OR, 5.39; 95% CI 2.90–10.05) and diabetes (OR, 2.02; 95% CI 1.03–3.97). Furthermore, predictors for mortality were aged 74–84 years (OR, 5.58; 95% CI 3.10–10.03) or ≥85 years (OR, 9.35, 95% CI 4.31–20.30), combined pulmonary and extra-pulmonary TB (OR, 4.97; 95% CI 1.42–17.41), central nervous system (OR, 120, 95% CI 34.43–418.54) or miliary TB (OR, 10.73, 95% CI 2.50–46.02), drug addiction (OR, 3.56; 95% CI 1.34–9.47) and renal insufficiency/dialysis (OR, 3.23; 95% CI 1.17–8.96).ConclusionsNative- and foreign-born patients exhibited similar TB treatment outcomes. To further reduce disease transmission and inhibit drug resistance, special attention should be given to high-risk patients.     

Effect of Dementia on Postoperative Mortality in Elderly Patients with Hip Fracture

BackgroundThe aim of this study was to assess the prevalence of dementia as an underlying disease in elderly patients with hip fracture, to investigate the effect of dementia on postoperative mortality after surgery of hip fracture, and to analyze the differences in postoperative mortalities according to the severity of dementia through subgroup analysis.MethodsThis study selected 2,346 elderly patients who were diagnosed with unilateral intertrochanteric or femoral neck fractures who underwent surgery between January 2004 and December 2018. The patients were classified into the non-dementia group (2,196 patients) and dementia group (150 patients; no-medication [66 patients] and medication [84 patients] subgroups). The cumulative crude mortality rate was calculated, and 30-day, 60-day, 3-month, 6-month, and 1-year mortality rates were compared between the groups. A univariate regression test was performed using age, sex, diagnosis, surgery type, and Charlson''s comorbidity index (CCI), as these variables had P values of < 0.10. Multivariate regression analysis was performed to identify independent risk factors associated with mortality.ResultsThe 30-day, 60-day, 3-month, 6-month, and 1-year postoperative cumulative mortality rates were 1.8%, 3.8%, 5.6%, 8.9%, and 13.6%, respectively, in the non-dementia group, and 2%, 7.3%, 14%, 19.3%, and 24%, respectively, in the dementia group (P = 0.748, P = 0.048, P < 0.001, P < 0.001, and P = 0.001). The factors that affected the 1-year mortality were age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.08; P < 0.001), sex (OR, 2.68; 95% CI, 2.07–3.47; P < 0.001), CCI (OR, 1.34; 95% CI, 1.23–1.47; P < 0.001), and dementia (OR, 1.70; 95% CI, 1.46–1.08; P = 0.016). In subgroup analysis, severity of dementia influenced the 6-month mortality (OR, 1.41; 95% CI, 1.70–2.01; P = 0.018), and 1-year mortality (OR, 1.30; 95% CI, 1.17–1.90; P = 0.027).ConclusionIn elderly hip fracture patients, the comparison between patients with and without dementia revealed that dementia was an independent risk factor for mortality at a minimum of 1 year of follow-up, and the severity of dementia in hip fracture patients was a risk factor for mortality within 6 months and 1 year, postoperatively.     

Pneumocystis jiroveci pneumonia in Taiwan from 2014 to 2017: Clinical manifestations and outcomes between pediatric and adult patients

BackgroundPneumocystis jiroveci pneumonia (PJP) is a severe and lethal opportunistic infection in the immunocompromised patients. As the increasing usage of immunosuppressants, the incidence of non-HIV related PJP has increased in recent years. Still, there is little research regarding children with PJP. The aim of this study is to understand PJP more among pediatric population.MethodsWe reviewed the medical records of the patients with PJP in National Taiwan University Hospital from 2014 to 2017. Diagnosis was made if the patient met all of the criteria: presence of relevant pulmonary symptoms and signs, pulmonary infiltrates on images, detection of Pneumocystis jiroveci from respiratory specimens via polymerase chain reaction (PCR), and received antibiotics for PJP.ResultsTwenty children and 132 adults were enrolled in this study. The most common underlying diseases among children included malignancy (40%), post-transplantation (30%), and primary immunodeficiency (20%). The major underlying diseases in adults included malignancy (36%), HIV with acquired immunodeficiency syndrome (AIDS) (31%), and autoimmune diseases (24%). There is no significant difference in the clinical manifestations, mortality, and complication between children and adults, but children tended to have less chance of using alternative antibiotics, methylprednisolone and inhaled nitric oxide (NO). The chance of concomitant cytomegalovirus disease was also significantly lower in pediatric patients.ConclusionNo significant difference was found in the clinical manifestations, mortality, and complication between children and adults, but children tended to have lesser chance of using alternative antibiotics, methylprednisolone and inhaled NO. The chance of associated cytomegalovirus (CMV) disease was also significantly lower in children.     

The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality.DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.     

Cerebrovascular accidents differ between patients with atrial flutter and patients with atrial fibrillation

IntroductionFew studies have explored the potential impact of atrial flutter (AFl) on ischaemic stroke (IS) outcome. The aim of the present study was to compare the clinical course of IS in patients with AFl and patients with atrial fibrillation (AF).Material and methodsA retrospective analysis of patients consecutively admitted to a tertiary care centre between 2013 and 2015 due to IS or transient ischaemic attack with permanent AFl or permanent or persistent AF was performed.ResultsThe study groups consisted of 528 patients, including 490 (92.8%) patients with AF and 38 (7.2%) patients with AFl. The mean age and prestroke CHA2DS2-VASc scores were similar between the patients with AFl and those with AF. Most IS cases in the AF group were classified as cardioembolic strokes (74.9% vs. 39.5% in AFl, p < 0.01), and lacunar strokes were the most common in the AFl group (47.4% vs. 14.3% in AF, p < 0.01). The multivariable analysis revealed that the presence of AF (OR = 8.6, 95% CI: 1.2–57, p = 0.02), lacunar stroke (OR = 0.1, 95% CI: 0.03–0.31, p < 0.001), baseline Rankin scale score (OR = 16.6, 95% CI: 9.8–28), lack of prestroke therapeutic anticoagulation (OR = 6.1, 95% CI: 1.1–33), diabetes (OR = 2.9, 95% CI: 1.3–6.5, p < 0.01), chronic heart failure (OR = 14.2, 95% CI: 5.8–34, p < 0.001), and current smoking (OR = 0.92, 95% CI: 0.39–0.99, p < 0.01) were significantly associated with the stroke outcome.ConclusionsDisabling or fatal IS was observed less often in patients with AFl than in patients with AF. This finding can possibly be explained by the more frequent occurrence of lacunar strokes in the AFl group compared with that in the AF group.     

Improved COVID-19 ICU admission and mortality outcomes following treatment with statins: a systematic review and meta-analysis

IntroductionApproximately 1% of the world population has now been infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). With cases still rising and vaccines just beginning to rollout, we are still several months away from seeing reductions in daily case numbers, hospitalisations, and mortality. Therefore, there is a still an urgent need to control the disease spread by repurposing existing therapeutics. Owing to antiviral, anti-inflammatory, immunomodulatory, and cardioprotective actions, statin therapy has been considered as a plausible approach to improve COVID-19 outcomes.Material and methodsWe carried out a meta-analysis to investigate the effect of statins on 3 COVID-19 outcomes: intensive care unit (ICU) admission, tracheal intubation, and death. We systematically searched the PubMed, Web of Science, Scopus, and ProQuest databases using keywords related to our aims up to November 2, 2020. All published observational studies and randomised clinical trials on COVID-19 and statins were retrieved. Statistical analysis with random effects modelling was performed using STATA16 software.ResultsThe final selected studies (n = 24 studies; 32,715 patients) showed significant reductions in ICU admission (OR = 0.78, 95% CI: 0.58–1.06; n = 10; I² = 58.5%) and death (OR = 0.70, 95% CI: 0.55–0.88; n = 21; I² = 82.5%) outcomes, with no significant effect on tracheal intubation (OR = 0.79; 95% CI: 0.57–1.11; n = 7; I²= 89.0%). Furthermore, subgroup analysis suggested that death was reduced further by in-hospital application of stains (OR = 0.40, 95% CI: 0.22–0.73, n = 3; I² = 82.5%), compared with pre-hospital use (OR = 0.77, 95% CI: 0.60–0.98, n = 18; I² = 81.8%).ConclusionsThese findings call attention to the need for systematic clinical studies to assess both pre- and in-hospital use of statins as a potential means of reducing COVID-19 disease severity, particularly in terms of reduction of ICU admission and total mortality reduction.     

β-d-Glucan kinetics for the assessment of treatment response in Pneumocystis jirovecii pneumonia

Serum (1→3)-β-d-Glucan (BG) is a biomarker for Pneumocystis jirovecii pneumonia (PJP). However, information concerning its usefulness for monitoring the clinical course is lacking. We conducted a retrospective study to investigate whether consecutive BG-measurements can be used to assess treatment response in PJP. Analysis of sera from 18 patients during PJP therapy shows that decreasing BG-levels strongly correlate with a favourable clinical course. In contrast, increasing BG-levels were associated with treatment failure or fatal outcome is only 44% of patients. As a consequence, BG-kinetics might be used to confirm treatment success but seem to be of limited value for the identification of treatment failure.     

Unmasking Granulomatous Pneumocystis jirovecii Pneumonia with Nodular Opacity in an HIV-Infected Patient after Initiation of Antiretroviral Therapy

Pneumocystis jirovecii pneumonia (PJP) in patients with HIV infection can, in rare cases, present with pulmonary nodules that histologically involve granulomatous inflammation. This report describes an intriguing case of granulomatous PJP with pulmonary nodules after commencing antiretroviral therapy (ART) in an HIV-infected patient without respiratory signs or symptoms. Diagnosis of granulomatous PJP was only achieved through thoracoscopic lung biopsy. This case suggests that granulomatous PJP should be considered in the differential diagnosis of pulmonary nodules in HIV-infected patients for unmasking immune reconstitution inflammatory syndrome manifestation after initiation of ART.     

A multicenter study on clinical characteristics of Acinetobacter bacteremia in patients with liver cirrhosis

BackgroundClinical characteristics and risk factors for mortality of Acinetobacter bacteremia in cirrhotic patients have not been investigated.MethodsAcinetobacter bacteremia cases from four medical centers were collected from 2009 to 2014, to compare between patients with and without liver cirrhosis. Risk factors for mortality of Acinetobacter bacteremia among cirrhotic patients were identified using multivariate logistic regression.ResultsAmong the patients with Acinetobacter bacteremia, 72 had liver cirrhosis and 816 had not. Patients with cirrhosis were younger (57.5 [50–71] vs. 72 [50.25–71], p < 0.001), had more solid tumor (51.4% vs. 31.4%, p = 0.001), lower Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (17 [12–24] vs. 20 [13–28], p = 0.012), less sourced from pneumonia (19.4% vs. 35.8%, p = 0.008), and less caused by Acinetobacter baumannii (33.3% vs. 50.6%, p = 0.007) than those without. After matching for age, sex, and causative pathogens, the 30-day mortality (34.7% vs. 29.2%, p = 0.592) and APACHE II scores (17 vs. 17, p = 0.769) were not significant. APACHE II score (odds ratio [OR], 1.146; 95% confidence interval [CI], 1.035–1.268; p = 0.009), bacteremia caused by A. baumannii (OR, 20.501; 95% CI, 2.301–182.649; p = 0.007), and solid tumor (OR, 18.073; 95% CI, 1.938–168.504; p = 0.011) were independent risk factors for 30-day mortality of cirrhotic patients with Acinetobacter bacteremia.ConclusionEven though cirrhotic patients with Acinetobacter bacteremia were younger and had lower APACHE II scores than non-cirrhotic patients, the mortality rates were insignificantly different between the two groups.     

Association of objectively measured sleep with frailty and 5-year mortality in community-dwelling older adults

Study ObjectivesTo determine whether actigraphy-measured sleep was independently associated with risk of frailty and mortality over a 5-year period among older adults.MethodsWe used data from Waves 2 (W2) and 3 (W3) (2010–2015) of the National Social Life, Health and Aging Project, a prospective cohort of community-dwelling older adults born between 1920 and 1947. One-third of W2 respondents were randomly selected to participate in a sleep study, of whom N = 727 consented and N = 615 were included in the analytic sample. Participants were instructed to wear a wrist actigraph for 72 h (2.93 ± 0.01 nights). Actigraphic sleep parameters were averaged across nights and included total sleep time, percent sleep, sleep fragmentation index, and wake after sleep onset. Subjective sleep was collected via questionnaire. Frailty was assessed using modified Fried Frailty Index. Vital status was ascertained at the time of the W3 interview. W3 frailty/mortality status was analyzed jointly with a four-level variable: robust, pre-frail, frail, and deceased. Associations were modeled per 10-unit increase.ResultsAfter controlling for baseline frailty (robust and pre-frail categories), age, sex, education, body mass index, and sleep time preference, a higher sleep fragmentation index was associated with frailty (OR = 1.70, 95% CI: 1.02–2.84) and mortality (OR = 2.12, 95% CI: 1.09–4.09). Greater wake after sleep onset (OR = 1.24, 95% CI: 1.02–1.50) and lower percent sleep (OR = 0.41, 95% CI: 0.17–0.97) were associated with mortality.ConclusionsAmong community-dwelling older adults, actigraphic sleep is associated with frailty and all-cause mortality over a 5-year period. Further investigation is warranted to elucidate the physiological mechanisms underlying these associations.     

Predictive Factors of Mortality in Population of Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Results from a Korean PNH Registry

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, systemic, life-threatening disease, characterized by chronic uncontrolled complement activation. A retrospective analysis of 301 Korean PNH patients who had not received eculizumab was performed to systematically identify the clinical symptoms and signs predictive of mortality. PNH patients with hemolysis (lactate dehydrogenase [LDH] ≥ 1.5 × the upper limit of normal [ULN]) have a 4.8-fold higher mortality rate compared with the age- and sex-matched general population (P < 0.001). In contrast, patients with LDH < 1.5 × ULN have a similar mortality rate as the general population (P = 0.824). Thromboembolism (TE) (odds ratio [OR] 7.11; 95% confidence interval [CI] (3.052-16.562), renal impairment (OR, 2.953; 95% CI, 1.116-7.818) and PNH-cytopenia (OR, 2.547; 95% CI, 1.159-5.597) are independent risk factors for mortality, with mortality rates 14-fold (P < 0.001), 8-fold (P < 0.001), and 6.2-fold (P < 0.001) greater than that of the age- and sex-matched general population, respectively. The combination of hemolysis and 1 or more of the clinical symptoms such as abdominal pain, chest pain, or dyspnea, resulted in a much greater increased mortality rate when compared with patients with just the individual symptom alone or just hemolysis. Early identification of risk factors related to mortality is crucial for the management of PNH. This trial was registered at www.clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT01224483","term_id":"NCT01224483"}}NCT01224483.     

The Distribution of Multidrug-resistant Microorganisms and Treatment Status of Hospital-acquired Pneumonia/Ventilator-associated Pneumonia in Adult Intensive Care Units: a Prospective Cohort Observational Study

BackgroundIt is essential to determine the distribution of the causative microorganisms in the region and the status of local antibiotic resistance for the proper treatment of hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP). This study aimed to investigate the occurrence and causative strains of HAP/VAP, distribution of resistant bacteria, use of antibiotics, and the ensuing outcomes of patients in Korea.MethodsA multicenter prospective observational cohort study was conducted among patients with HAP/VAP admitted to the medical intensive care unit of 5 tertiary referral centers between August 2012 and June 2015. Patients'' demographic and clinical data were collected.ResultsA total of 381 patients were diagnosed with HAP/VAP. Their median age was 69 (59–76) years and 71% were males. A majority of the patients (88%) had late-onset (> 5 days) HAP/VAP. One-quarter of the patients (n = 99) had at least one risk factor for multidrug-resistant (MDR) pathogens, such as prior intravenous antibiotic use within the last 90 days. Microbiological specimens were mostly obtained noninvasively (87%) using sputum or endotracheal aspirates. Pathogens were identified in 235 (62%) of the 381 patients. The most common bacterial pathogen was Acinetobacter baumannii (n = 89), followed by Staphylococcus aureus (n = 52), Klebsiella pneumoniae (n = 25) and Pseudomonas aeruginosa (n = 22). Most of isolated A. baumannii (97%) and S. aureus (88%) were multidrug resistant. The most commonly used empirical antibiotic regimens were carbapenem-based antibiotics (38%), followed by extended-spectrum penicillin/β-lactamase inhibitor (34%). Glycopeptide or linezolid were also used in combination in 54% of patients. The 28-day mortality rate of the patients with HAP/VAP was 30% and the 60-day mortality was 46%. Patients who used empirical antibiotics appropriately had significantly lower mortality rates than those who did not (28-day mortality: 25% vs. 40%, P = 0.032; 60-day mortality: 41% vs. 55%, P = 0.032, respectively). Administration of appropriate empirical antibiotics (odds ratio [OR], 0.282; confidence interval [CI], 0.092–0.859; P = 0.026), Day 7 treatment failure (OR, 4.515; CI, 1.545–13.192; P = 0.006), and APACHE II score on day 1 (OR, 1.326; CI, 0.988–1.779; P = 0.012) were the factors that determined the 28-day mortality in patients with HAP who had identified bacteria as pathogens.ConclusionIn HAP/VAP patients, there was a large burden of MDR pathogens, and their associated mortality rate was high. Proper selection of empirical antibiotics was significantly associated with the patient''s prognosis; however, there was a discrepancy between major pathogens and empirical antibiotic therapy.     

Invasive pulmonary aspergillosis is associated with cytomegalovirus viremia in critically ill patients - A retrospective cohort study

Background/PurposeCytomegalovirus (CMV) viremia is associated with a higher mortality rate and prolonged intensive care unit (ICU) stay for critically ill patients. CMV infection causes transient but substantial immunosuppression for transplant recipients, increasing risk of fungal infection. The association between CMV viremia and invasive pulmonary aspergillosis (IPA) for critically ill patients is still unknown.MethodsWe retrospectively analyzed patients received bronchoalveolar lavage (BAL), galactomannan test, influenza survey and blood CMV viral load test in ICUs of a university hospital between April 2017 and May 2020. Independent risks for IPA were analyzed by multivariable logistic regression.ResultsA total of 136 patients were included. Twenty-one patients had IPA, 48 patients had CMV viremia and 22 patients had influenza. In a multivariable logistic regression model, patients with CMV viremia or influenza had higher IPA risk (adjusted odds ratio, 3.98 and 8.72; 95% CI, 1.26–12.60 and 2.64–28.82; p value = 0.019 and <0.001, respectively.). Patients with detectable CMV in BAL fluid did not have higher IPA risk (crude odds ratio, 0.95; 95% CI, 0.33–2.79; p value = 0.933). After stratifying patients by CMV viral load, the IPA risk is higher for patients with higher viral loads. There is an additive synergistic effect on IPA risk between CMV viremia and influenza infection.ConclusionFor critically ill patients, CMV viremia is an independent risk factor of IPA. Patients with higher blood CMV viral loads have a higher risk of IPA. CMV viremia and influenza have an additive synergistic effect for IPA risk in critically ill patients.     

Incidence and Mortality Associated with Cardiovascular Medication among Hypertensive COVID-19 Patients in South Korea

PurposeWe aimed to investigate whether the use of cardiovascular drugs in coronavirus disease 2019 (COVID-19) patients with hypertension as a comorbidity has a significant effect on the incidence and associated mortality rate of COVID-19.Materials and MethodsData covering the period between January 1, 2020 and June 4, 2020 were extracted from The National Health Insurance Service-COVID-19 (NHIS-COVID-19) database in South Korea and analyzed as a population-based cohort study.ResultsA total of 101657 hypertensive adults aged 20 years or older were included for final analysis. Among them, 1889 patients (1.9%) were diagnosed with COVID-19 between January 1, 2020 and June 4, 2020, and hospital mortality occurred in 193 patients (10.2%). In a multivariable model, the use of beta-blockers was associated with an 18% lower incidence of COVID-19 [odds ratio (OR): 0.82, 95% confidence interval (CI): 0.69–0.98; p=0.029]. Among 1889 hypertensive patients diagnosed with COVID-19, the use of a calcium channel blocker (CCB) was associated with a 42% lower hospital mortality rate (OR: 0.58, 95% CI: 0.38–0.89; p=0.012). The use of other cardiovascular drugs was not associated with the incidence of COVID-19 or hospital mortality rate among COVID-19 patients. Similar results were observed in all 328374 adults in the NHIS-COVID-19 database, irrespective of the presence of hypertension.ConclusionIn South Korea, beta-blockers exhibited potential benefits in lowering the incidence of COVID-19 among hypertensive patients. Furthermore, CCBs may lower the hospital mortality rate among hypertensive COVID-19 patients. These findings were also applied to the general adult population, regardless of hypertension.     

Epidemiology and outcomes of bloodstream infections in 177 severe burn patients from an industrial disaster: a multicentre retrospective study

ObjectivesTo determine the characteristics of bloodstream infections (BSIs) and to evaluate the impact of BSIs on mortality in severe burn patients.MethodsA retrospective observational study was conducted in 20 tertiary hospitals. A total of 185 patients who experienced a massive dust explosion in eastern China were included.ResultsAfter exclusion, 177 patients were analysed. The median total body surface area (TBSA) burned was 95% (interquartile range 85%–98%). Inhalation injuries occurred in 97.2%. The overall 90-day mortality was 35% (62/177). During the study period, 120 (67.8%) patients developed 253 episodes of BSI with 323 unique causative pathogens. Sixty-six episodes were polymicrobial infections. Catheter-related BSIs (CRBSIs) accounted for 41.5% of the episodes. Acinetobacter baumannii (19.5%), Klebsiella pneumoniae (13.9%) and Candida (12.7%) were the most common organisms. Antimicrobial resistance was found in 63.5% of the isolates, particularly in Gram-negative bacteria. Patients who developed BSIs had a greater illness severity at admission to the intensive care unit, and worse outcomes. After adjusting for demographics, severity of illness and treatment characteristics in a multivariate logistic model, there was a trend toward BSI increasing the risk of 90-day mortality (adjusted OR 3.4; 95% CI 0.9–12.9; p=0.069). In subgroup analyses, CRBSIs (adjusted OR 5.7; 95% CI 1.3–24.9; p=0.021 versus no BSI) and polymicrobial BSIs (adjusted OR 6.1; 95% CI 1.3–28.1; p=0.020 versus no BSI) had greater risk of 90-day mortality.ConclusionsA strikingly high rate of BSIs was observed in severe burn patients. Gram-negative organisms and fungi were the leading causes. CRBSIs and polymicrobial BSIs were associated with high mortality.