Recovery of right ventricular function after intermediate-risk pulmonary embolism: results from the multicentre Pulmonary Embolism International Trial (PEITHO)-2.

BACKGROUND: Right ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort of a prospective multicentre study investigating if an early switch to oral anticoagulation in patients with intermediate-risk PE is effective and safe. METHODS: Echocardiographic and laboratory examinations were performed at baseline (PE diagnosis), 6 days and 6 months. Echocardiographic parameters were classified into categories representing RV size, RV free wall/tricuspid annulus motion, RV pressure overload and right atrial (RA)/central venous pressure. RESULTS: RV dysfunction based on any abnormal echocardiographic parameter was present in 84% of patients at baseline. RV dilatation was the most frequently abnormal finding (40.6%), followed by increased RA/central venous pressure (34.6%), RV pressure overload (32.1%), and reduced RV free wall/tricuspid annulus motion (20.9%). As early as day 6, RV size remained normal or improved in 260 patients (64.7%), RV free wall/tricuspid annulus motion in 301 (74.9%), RV pressure overload in 297 (73.9%), and RA/central venous pressure in 254 (63.2%). At day 180, the frequencies slightly increased. The median NT-proBNP level decreased from 1448 pg/ml at baseline to 256.5 on day 6 and 127 on day 180. CONCLUSION: In the majority of patients with acute intermediate-risk PE switched early to a direct oral anticoagulant, echocardiographic parameters of RV function normalised within 6 days and remained normal throughout the first 6 months. Almost one in four patients, however, continued to have evidence of RV dysfunction over the long term.

Early administration of tofacitinib in COVID-19 pneumonitis: An open randomised controlled trial.

BACKGROUND: Controversies on sub-populations most sensitive to therapy and the best timing of starting the treatment still surround the use of immunomodulatory drugs in COVID-19. OBJECTIVES: We designed a multicentre open-label randomised controlled trial to test the effect of prompt adding of tofacitinib to standard therapy for hospitalised patients affected by mild/moderate COVID-19 pneumonitis. METHODS: Patients admitted to three Italian hospitals affected by COVID-19 pneumonitis not requiring mechanical ventilation were randomised to receive standard treatment alone or tofacitinib (10 mg/bid) for 2 weeks, starting within the first 24 h from admission. RESULTS: A total of 116 patients were randomised; 49 in the experimental arm completed the 14-day treatment period, 9 discontinued tofacitinib as the disease worsened and were included in the analysis, and 1 died of respiratory failure. All 58 control patients completed the study. Clinical and demographic characteristics were similar between the study groups. In the tofacitinib group, 9/58 (15.5%) patients progressed to noninvasive ventilation (CPAP) to maintain SO2 > 93%, invasive mechanical ventilation or death by day 14 was 15.5%, significantly less than in the control group (20/58, 34.4%, RR 0,45, RRR -55%, NNT 5; p = .018). No differences in severe adverse effect incidence had been observed across the groups. CONCLUSION: High-dose tofacitinib therapy in patients with COVID pneumonitis is safe and may prevent deterioration to respiratory failure.

Echocardiographic predictors of mortality in intermediate-risk pulmonary embolism.

Data regarding further risk stratification of intermediate-risk pulmonary embolism (IR-PE) are scanty. Whether transthoracic echocardiography may be helpful in further risk assessment of death in such population has still to be proven. Two-hundred fifty-four consecutive patients (51.6% females, age 63.7 ± 17.3 years) with IR-PE admitted to a tertiary regional referral center were enrolled. Patients underwent a complete transthoracic echocardiography within 36 h from hospital admission, on top of clinical assessment, physical examination, computer tomography pulmonary angiography (CTPA), and serum measurement of Troponin I (TnI) levels. The occurrence of 90 day mortality was chosen as primary outcome measure. When compared to survivors, non-surviving IR-PE patients had smaller left-ventricular end-diastolic volumes (39.8 ± 20.9 vs 49.4 ± 19.9 ml/m2, p = 0.006) with reduced stroke volume index (SVi) (24.7 ± 10.9 vs 30.9 ± 12.6 ml/m2, p: 0.004) and time-velocity integral at left-ventricular outflow tract (VTILVOT) (0.17 ± 0.03 vs 0.20 ± 0.04 m, p = 0.0001), whereas no differences were recorded regarding right heart parameters. Cox regression analysis revealed that right atrial enlargement (RAE) (HR 3.432, 5-95% CI 1.193-9.876, p: 0.022), the ratio between tricuspid annulus plane excursion and pulmonary arterial systolic pressure (TAPSE/PASp) (HR 4.833, 5-95% 1.230-18.986, p = 0.024), as well as SVi (HR 11.199, 5-95% CI 2.697-48.096, p = 0.001) and VTILVOT (HR 4.212, 5-95% CI 1.384-12.820, p = 0.011) were powerful independent predictors of mortality. Neither CTPA RV/LV nor TnI resulted associated with impaired survival. In intermediate-risk pulmonary embolism, RAE, TAPSE/PASp ratio, SVi, and VTILVOT predict independently prognosis to a greater extent than CTPA and TnI.

Risk prediction of clinical adverse outcomes with machine learning in a cohort of critically ill patients with atrial fibrillation.

Critically ill patients affected by atrial fibrillation are at high risk of adverse events: however, the actual risk stratification models for haemorrhagic and thrombotic events are not validated in a critical care setting. With this paper we aimed to identify, adopting topological data analysis, the risk factors for therapeutic failure (in-hospital death or intensive care unit transfer), the in-hospital occurrence of stroke/TIA and major bleeding in a cohort of critically ill patients with pre-existing atrial fibrillation admitted to a stepdown unit; to engineer newer prediction models based on machine learning in the same cohort. We selected all medical patients admitted for critical illness and a history of pre-existing atrial fibrillation in the timeframe 01/01/2002-03/08/2007. All data regarding patients' medical history, comorbidities, drugs adopted, vital parameters and outcomes (therapeutic failure, stroke/TIA and major bleeding) were acquired from electronic medical records. Risk factors for each outcome were analyzed adopting topological data analysis. Machine learning was used to generate three different predictive models. We were able to identify specific risk factors and to engineer dedicated clinical prediction models for therapeutic failure (AUC: 0.974, 95%CI: 0.934-0.975), stroke/TIA (AUC: 0.931, 95%CI: 0.896-0.940; Brier score: 0.13) and major bleeding (AUC: 0.930:0.911-0.939; Brier score: 0.09) in critically-ill patients, which were able to predict accurately their respective clinical outcomes. Topological data analysis and machine learning techniques represent a concrete viewpoint for the physician to predict the risk at the patients' level, aiding the selection of the best therapeutic strategy in critically ill patients affected by pre-existing atrial fibrillation.

Chronic Respiratory Diseases and Neurodegenerative Disorders: A Primer for the Practicing Clinician.

Chronic respiratory disorders represent a world epidemic. Their incidence and prevalence in the world population is increasing, and especially among elderly subjects, they are commonly associated with other pathologies, often generating a status of high clinical complexity. Neurology, internal medicine, and pneumology specialists should be aware of the common background of these disorders in order to treat correctly the patient's comorbid state and optimize the treatment considering potential overlaps. In this review, we aimed to focus on the relationships between chronic respiratory disorders and chronic neurodegenerative diseases at different levels; we review the shared risk factors and the interactions between disorders, the indications to explore respiratory function in neurodegenerative diseases, pathology-pathology and drug-pathology interactions in patients affected by both chronic neurologic and respiratory diseases.

Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial.

BACKGROUND: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe. METHODS: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555). FINDINGS: Between Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0-78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210-224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p<0·0001 for rejecting the null hypothesis) patients, with all events occurring in those with intermediate-high-risk pulmonary embolism (seven [3%; upper bound of right-sided 95% CI 5] of 283). At 6 months, 11 (3% [95% CI 1-5]) of 402 patients had at least one major bleeding event and 16 (4% [2-6]) had at least one clinically relevant non-major bleeding event; the only fatal haemorrhage occurred in one (<1%) patient before the switch to dabigatran. INTERPRETATION: A strategy of early switch from heparin to dabigatran following standard clinical assessment was effective and safe in patients with intermediate-risk pulmonary embolism. Our results can help to refine guideline recommendations for the initial treatment of acute intermediate-risk pulmonary embolism, optimising the use of resources and avoiding extended hospitalisation. FUNDING: German Federal Ministry of Education and Research, University Medical Center Mainz, and Boehringer Ingelheim.

Clinical Method Applied to Focused Ultrasound: The Case of Wells' Score and Echocardiography in the Emergency Department: A Systematic Review and a Meta-Analysis.

Background and Objectives: bedside cardiac ultrasound is a widely adopted method in Emergency Departments (ED) for extending physical examination and refining clinical diagnosis. However, in the setting of hemodynamically-stable pulmonary embolism, the diagnostic role of echocardiography is still the subject of debate. In light of its high specificity and low sensitivity, some authors suggest that echocardiographic signs of right ventricle overload could be used to rule-in pulmonary embolism. In this study, we aimed to clarify the diagnostic role of echocardiographic signs of right ventricle overload in the setting of hemodynamically-stable pulmonary embolism in the ED. Materials and Methods: we performed a systematic review of literature in PubMed, Web of Science and Cochrane databases, considering the echocardiographic signs for the diagnosis of pulmonary embolism in the ED. Studies considering unstable or shocked patients were excluded. Papers enrolling hemodynamically stable subjects were selected. We performed a diagnostic test accuracy meta-analysis for each sign, and then performed a critical evaluation according to pretest probability, assessed with Wells' score for pulmonary embolism. Results: 10 studies were finally included. We observed a good specificity and a low sensitivity of each echocardiographic sign of right ventricle overload. However, once stratified by the Wells' score, the post-test probability only increased among high-risk patients. Conclusions: signs of echocardiographic right ventricle overload should not be used to modify the clinical behavior in low- and intermediate- risk patients according to Wells' score classification. Among high-risk patients, however, echocardiographic signs could help a physician in detecting patients with the highest probability of pulmonary embolism, necessitating a confirmation by computed tomography with pulmonary angiography. However, a focused cardiac and thoracic ultrasound investigation is useful for the differential diagnosis of dyspnea and chest pain in the ED.

Patient-Reported Outcome Measurements (PROMs) After Discharge From the Emergency Department: A Cross-Sectional Study.

BACKGROUND: The purpose of a patient-reported outcome (PRO) is to elicit the perspectives of patients and translate them into a reliable measurement questionnaire. OBJECTIVES: The objective of this cross-sectional study was to detect a set of PROs and PRO measurements (PROMs) about patients with isolated trauma of the limbs receiving emergency department (ED) care. METHODS: A survey was performed in the ED using a questionnaire among the enrolled patients to identify which proposed outcomes were perceived as important by the patients according to their expectations. RESULTS: Ninety-six consecutive patients were conveniently enrolled. For each item of the questionnaire, the percentage of patients who agreed to perceive it important were calculated. Three items were perceived important by almost 85% of the patients: getting an x-ray (91%; 95% CI: 88%-98%), obtaining a written therapy (94%; 95% CI: 87%-97%), and feeling the physicians' and nurses' empathy (97%; 95% CI: 91%-99%). The ED system was able to satisfy 2 of the 3 agreed PROs in at least 85% of the cases: getting an x-ray (97%; 95% CI: 91%-99%) and obtaining a written therapy (97%; 95% CI: 91%-99%). Moreover, in 30/96 patients (31%; 95% CI: 22%-41%), all the PROs were satisfied, and in 75/96 patients (78%; 95% CI: 69%-85%), all agreed PROs were satisfied. CONCLUSIONS: Our study shows an example of core of PROs proposed by the ED physicians and agreed by the patients. Moreover, we presented a set of PROMs which could be used to measure the quality of an ED.

Predictors of readmission requiring hospitalization after discharge from emergency departments in patients with COVID-19.

INTRODUCTION: Little is known on prevalence of early return hospital admission of subjects with COVID-19 previously evaluated and discharged from emergency departments (EDs). This study aims to describe readmission rate within 14 days of patients with COVID-19 discharged from ED and to identify predictors of return hospital admission. METHODS: We performed a retrospective cohort study of adult patients with COVID-19 discharged from two EDs. Return hospital admission was defined as an unscheduled return ED visit within 14 days after initial ED evaluation and discharge. We compared the group of patients who had a return hospital admission to those who did not. We also evaluated selected clinical characteristics (age, neutrophilia, SOFA, lactate dehydrogenase, C-reactive protein and D-dimer) associated with return hospital admission. RESULTS: Of 283 patients included in the study, 65 (22.9%) had a return ED visit within 14 days. 32 of those patients (11%) were then hospitalized, while the remaining 33 were again discharged. Patients requiring a return hospital admission was significantly older, had higher pro-calcitonin and D-dimer levels. Major predictors of return hospital admission were cognitive impairment (OR 17.3 [CI 4.7-63.2]), P/F < 300 mmHg (OR 8.6 [CI 1.6-44.3]), being resident in geriatric care facility (OR 7.6 [CI 2.1-26.4]) and neutrophilia (OR 5.8 [CI 1.6-22.0]). CONCLUSION: Several factors are associated with 14-day return hospital admission in COVID-19 subjects. These should be considered when assessing discharge risk in ED clinical practice.

Diagnosis and Treatment of Deep Vein Thrombosis in the Emergency Department: Results of an Italian Nominal Group Technique Study.

Early diagnosis and treatment of deep vein thrombosis (DVT) is a main issue in the Emergency setting. With the aim of assisting clinicians in the diagnosis and the subsequent management of DVT in the Emergency Departments, a Nominal Group Technique (NGT) study was conducted. A panel of 5 Italian experts developed 21 consensus statements based on available evidence and their clinical experience. The agreed consensus statements may assist clinicians in applying the results of clinical studies and clinical experience to routine care settings, providing guidance on all aspects of the risk assessment, prophylaxis, early diagnosis and appropriate treatment of DVT in the EDs.

SOFA and qSOFA usefulness for in-hospital death prediction of elderly patients admitted for suspected infection in internal medicine.

PURPOSE: To reduce intensive care unit overcrowding and optimize resources, elderly patients affected by suspected infection with declining clinical conditions could be managed in internal medicine departments with stepdown beds. However, commonly used prognostic scores, as Sequential Organ Failure Assessment (SOFA) or quick SOFA (qSOFA) have never been studied in this specific setting. The aim of this study was to evaluate the role and the accuracy of SOFA and qSOFA as prognostic scores in a population of elderly patients with suspected infection admitted to stepdown beds of two internal medicine departments. METHODS: Elderly patients admitted from the emergency department in the stepdown beds of two different internal medicine departments for suspected infection were assessed with SOFA and qSOFA scores at the admission. All patients were treated according to current guidelines. Age, sex, comorbidities, Charlson comorbidity index, SOFA and qSOFA were assessed. In-hospital death and length of hospital admission were also recorded. RESULTS: 390 subjects were enrolled. In-hospital death occurred in 144 (36.9%) patients; we observed that both SOFA (HR 1.189; 95% CI 1.128-1.253; p < 0.0001) and qSOFA (HR 1.803; 95% CI 1.503-2.164; p < 0.0001) scores were independently associated with an increased risk of in-hospital death. However, the accuracy of both SOFA (AUC: 0.686; 95% CI 0.637-0.732; p < 0.0001) and qSOFA (AUC: 0.680; 95% CI 0.641-0.735; p < 0.0001) in predicting in-hospital death was low in this population. CONCLUSION: Elderly patients admitted to stepdown beds for suspected infection experience a high rate of in-hospital death; both SOFA and qSOFA scores can be useful to identify a group of patients who can benefit from admission to an intermediate care environment, however their accuracy is low.

Impact of atrial fibrillation in critically ill patients admitted to a stepdown unit.

BACKGROUND: Limited data are available on the clinical course of patients with history of atrial fibrillation (AF) when admitted in an intensive care environment. We aimed to describe the occurrence of major adverse events in AF patients admitted to a stepdown care unit (SDU) and to analyse clinical factors associated with outcomes, impact of dicumarolic oral anticoagulant (OAC) therapy impact and performance of clinical risk scores in this setting. MATERIALS AND METHODS: Single-centre, observational retrospective analysis on a population of subjects with AF history admitted to a SDU. Therapeutic failure (composite of transfer to ICU or death) was considered the main study outcome. Occurrence of stroke and major bleeding (MH) was considered as secondary outcomes. The performance of clinical risk scores was evaluated. RESULTS: A total of 1430 consecutive patients were enrolled. 194 (13.6%) reported the main outcome. Using multivariate logistic regression, age (odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.01-1.05), acute coronary syndrome (OR:3.10, 95% CI: 1.88-5.12), cardiogenic shock (OR:10.06, 95% CI: 5.37-18.84), septic shock (OR:5.19,95%CI:3.29-18.84), acute respiratory failure (OR:2.49, 95% CI: 1.67-3.64) and OAC use (OR: 1.61, 95% CI: 1.02-2.55) were independently associated with main outcome. OAC prescription was associated with stroke risk reduction and to both MH and main outcome risk increase. CHA2 DS2 -VASc (c-index: 0.545, P = .117 for stroke) and HAS-BLED (c-index:0.503, P = .900 for MH) did not significantly predict events occurrence. CONCLUSIONS: In critically ill AF patients admitted to a SDU, adverse outcomes are highly prevalent. OAC use is associated to an increased risk of therapeutic failure, clinical scores seem unhelpful in predicting stroke and MH, suggesting a highly individualized approach in AF management in this setting.

The Prognostic Role of Procalcitonin in Critically Ill Patients Admitted in a Medical Stepdown Unit: A Retrospective Cohort Study.

Procalcitonin (PCT) is a a marker of bacterial infection. Its prognostic role in the critically-ill patient, however, is still object of debate. Aim of this study was to evaluate the capacity of admission PCT (aPCT) in assessing the prognosis of the critically-ill patient regardless the presence of bacterial infection. A single-cohort, single-center retrospective study was performed evaluating critically-ill patients admitted to a stepdown care unit. Age, sex, Simplified Acute Physiology Score II (SAPS-II), shock, troponin-I, aPCT, serum creatinine, cultures and clinical endpoints (in-hospital mortality or Intensive Care Unit (ICU) transfer) were collected. Time free from adverse event (TF-AE) was defined as the time between hospitalization and occurrence of one of the clinical endpoints, and calculated with Kaplan-Meier curves. We engineered a new predictive model (POCS) adopting aPCT, age and shock.We enrolled 1063 subjects: 450 reached the composite outcome of death or ICU transfer. aPCT was significantly higher in this group, where it predicted TF-AE both in septic and non-septic patients. aPCT and POCS showed a good prognostic performance in the whole sample, both in septic and non-septic patients. aPCT showed a good prognostic accuracy, adding informations on the rapidity of clinical deterioration. POCS model reached a performance similar to SAPS-II.

Pulmonary embolism: a retrospective comparative study between patients with atypical vs typical clinical presentation

Background: Natural history and outcomes of patients with pulmonary embolism (PE) without typical symptoms (atypical PE) remain unclear. The aim of the study is to compare the clinical characteristics and the prognosis between typical PE and atypical PE. Methods: We retrospectively analyzed data from consecutive patients admitted to the Emergency Department (ED) because of a diagnosis of PE and classified them in two groups: typical PE and atypical PE. We defined PE to be typical in presence of almost one of the following symptoms or signs: dyspnea, chest pain, hemoptysis or signs of deep vein thrombosis. Results: Of the 191 patients with PE, 154 (81%) had typical PE and 37 (19%) had atypical PE. Patients with atypical and typical PE seemed to had similar prognostic factor such as high risk sPESI (73% vs 65%, p=0.3), right ventricular dysfunction (30% vs 26%, p=0.6) and central PE at chest CT scan (38% vs 36%, p=0.8). The rate of 30 day mortality was 7% in the typical group and 8% in the atypical group (p=0.8). The length of stay in hospital was the same in the two groups (6 days; p=0.2). Conclusions: We found that atypical and typical PE seem to be related diseases with a similar short term prognosis. Therefore, we could speculate that a missed diagnosis of PE in ED could expose the patients to a worsen prognosis. Further perspective studies are required for better investigate this diagnostic challenge.

Incomplete echocardiographic recovery at 6 months predicts long-term sequelae after intermediate-risk pulmonary embolism. A post-hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial.

INTRODUCTION: Symptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which patients should be followed after acute PE, when follow-up should be performed, and which tests it should include. Definition and classification of late PE sequelae are evolving, and their predictors remain to be determined. METHODS: In a post hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial, we focused on 219 survivors of acute intermediate-risk PE with clinical and echocardiographic follow-up 6 months after randomisation as well as over the long term (median, 3 years after acute PE). The primary outcome was a composite of (1) confirmed chronic thromboembolic pulmonary hypertension (CTEPH) or (2) 'post-PE impairment' (PPEI), defined by echocardiographic findings indicating an intermediate or high probability of pulmonary hypertension along with New York Heart Association functional class II-IV. RESULTS: Confirmed CTEPH or PPEI occurred in 29 (13.2%) patients, (6 with CTEPH and 23 with PPEI). A history of chronic heart failure at baseline and incomplete or absent recovery of echocardiographic parameters at 6 months predicted CTEPH or PPEI at long-term follow-up. CONCLUSIONS: CTEPH or PPEI occurs in almost one out of seven patients after acute intermediate-risk PE. Six-month echocardiographic follow-up may be useful for timely detection of late sequelae.

Management of spontaneous soft-tissue hemorrhage secondary to anticoagulant therapy: A cohort study.

STUDY OBJECTIVE: The optimal management of patients receiving heparin, warfarin or direct anti-coagulant therapy who experience spontaneous, severe, life-threatening soft-tissue hemorrhage (SSTH) is unclear. The purpose of this study is to investigate efficacy and safety of the interventional protocol implemented in our department. METHODS: In this retrospective cohort study, we analyzed data from 80 consecutive patients with SSTH secondary to anticoagulation therapy diagnosed by the appropriate computed tomography scan. All patients received a structured clinical pathway, including aggressive resuscitation, reversal of coagulopathy when indicated, Interventional Radiology procedures by transcatheter embolization (TE), clinical observation and repeated laboratory controls. RESULTS: We enrolled 80 patients from 2013 to 2017. Angiography was performed in 60 patients (75%). It revealed the bleeding site in 46 cases, and a TE was performed in all. The rates of technical success of TE, primary clinical success and bleeding control were 98% (45/46), 91% (73/80) and 89% (71/80) respectively. In 5 patients (6%) the control of the bleeding was obtained with a second TE. Short-term and 30-day mortality was 5% (4 patients) and 11% (9 patients), respectively. No adverse events were observed. CONCLUSION: A structured clinical pathway, including TE seems to be an effective and safe method to manage the patients with SSTH due to anticoagulant treatment.

Candidemia in the elderly: What does it change?

BACKGROUND: Candidemia is a life-threatening fungal infection and it can affect patients of all ages. Characterization of candidemia in the elderly is lacking. METHODS: We performed a retrospective study of adults (≥ 18 years) with candidemia diagnosed in our center in 2010-2015. Demographics, comorbidities, clinical and microbiologic characteristics, antifungal treatment and outcome were compared between older (≤65 years) and younger (>65 years) patients. RESULTS: Among 302 patients with candidemia identified during the study period, 188 (62%) belonged to the elderly group. Comorbidities were significantly more frequent in older patients and included chronic pulmonary diseases, cardiovascular diseases, diabetes mellitus, and chronic renal failure (p ranging from <0.0001 to 0.017). A significantly higher proportion of older patients had septic shock (p = 0.040) at the time of candidemia. Candida albicans accounted for 53% of isolates and there were no significant differences between patients' age and Candida species. Thirty-day mortality was significantly higher in older (45%) than in younger (28%) patients (p = 0.003). Factors associated with a significant higher proportion of death in the elderly included older age (i.e.: old-old), being hospitalized in ICU rather than in other wards, suffering from chronic pulmonary diseases, the presence of septic shock, multiple organ failure, dialysis and being infected with C. glabrata (p ranging from <0.0001 to 0.034). On multivariate analysis septic shock (HR 1.744 [CI95% 1.049-2.898], p = 0.032) and multiple organ failure (HR 2.242 [CI95% 1.070-4.698], p = 0.032) were independently associated with a higher risk of death. The probability of 30-days survival of older patients was significantly reduced when compared to that of younger patients (p = 0.005) who did not receive any treatment. In the elderly, there was a trend toward higher MICs for fluconazole/C. albicans, fluconazole/C. glabrata, amphotericin B/C. albicans, and caspofungin/C. glabrata. CONCLUSIONS: In our study, we found that elderly patients with Candida bloodstream infections are characterized by a high mortality rate. In particular, the lack of any antifungal therapy as well as the occurrence of septic shock increased significantly the overall mortality. Additionally, we found that there was a trend of higher MIC for specific drug/Candida combination.

Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism.

BACKGROUND: The long-term effect of thrombolytic treatment of pulmonary embolism (PE) is unknown. OBJECTIVES: This study investigated the long-term prognosis of patients with intermediate-risk PE and the effect of thrombolytic treatment on the persistence of symptoms or the development of late complications. METHODS: The PEITHO (Pulmonary Embolism Thrombolysis) trial was a randomized (1:1) comparison of thrombolysis with tenecteplase versus placebo in normotensive patients with acute PE, right ventricular (RV) dysfunction on imaging, and a positive cardiac troponin test result. Both treatment arms received standard anticoagulation. Long-term follow-up was included in the third protocol amendment; 28 sites randomizing 709 of the 1,006 patients participated. RESULTS: Long-term (median 37.8 months) survival was assessed in 353 of 359 (98.3%) patients in the thrombolysis arm and in 343 of 350 (98.0%) in the placebo arm. Overall mortality rates were 20.3% and 18.0%, respectively (p = 0.43). Between day 30 and long-term follow-up, 65 deaths occurred in the thrombolysis arm and 53 occurred in the placebo arm. At follow-up examination of survivors, persistent dyspnea (mostly mild) or functional limitation was reported by 36.0% versus 30.1% of the patients (p = 0.23). Echocardiography (performed in 144 and 146 patients randomized to thrombolysis and placebo, respectively) did not reveal significant differences in residual pulmonary hypertension or RV dysfunction. Chronic thromboembolic pulmonary hypertension (CTEPH) was confirmed in 4 (2.1%) versus 6 (3.2%) cases (p = 0.79). CONCLUSIONS: Approximately 33% of patients report some degree of persistent functional limitation after intermediate-risk PE, but CTEPH is infrequent. Thrombolytic treatment did not affect long-term mortality rates, and it did not appear to reduce residual dyspnea or RV dysfunction in these patients. (Pulmonary Embolism Thrombolysis study [PEITHO]; NCT00639743).