Minor head injury in anticoagulated patients: performance of biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in the detection of intracranial injury. A prospective observational study.

OBJECTIVES: Data in literature indicate that in patients suffering a minor head injury (MHI), biomarkers serum levels could be effective to predict the absence of intracranial injury (ICI) on head CT scan. Use of these biomarkers in case of patients taking oral anticoagulants who experience MHI is very limited. We investigated biomarkers as predictors of ICI in anticoagulated patients managed in an ED. METHODS: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The outcome was delayed ICI (dICI), defined as ICI on the second CT scan after a first negative CT scan. We assessed the sensitivity (SE), specificity (SP), negative predictive value (NNV) and positive predictive value (PPV) of the biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in order to identify dICI. RESULTS: Our study population was of 234 patients with a negative first CT scan who underwent a second CT scan. The rate of dICI was 4.7 %. The NPV for the detection of dICI were respectively (IC 95 %): S100B 92.7 % (86.0-96.8 %,); ubiquitin C-terminal hydrolase-L1 (UCH-L1) 91.8 % (83.8-96.6 %); glial fibrillary protein (GFP) 100 % (83.2-100 %); TBI 100 % (66.4-100 %). The AUC for the detection of dICI was 0.407 for S100B, 0.563 for neuron-specific enolase (NSE), 0.510 for UCH-L1 and 0.720 for glial fibrillary acidic protein (GFAP), respectively. CONCLUSIONS: The NPV of the analyzed biomarkers were high and they potentially could limit the number of head CT scan for detecting dICI in anticoagulated patients suffering MHI. GFAP and Alinity TBI seem to be effective to rule out a dCI, but future trials are needed.

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.

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.

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.

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.

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.

Acute pulmonary embolism: mortality prediction by the 2014 European Society of Cardiology risk stratification model.

The European Society of Cardiology (ESC) has proposed an updated risk stratification model for death in patients with acute pulmonary embolism based on clinical scores (Pulmonary Embolism Severity Index (PESI) or simplified PESI (sPESI)), right ventricle dysfunction (RVD) and elevated serum troponin (2014 ESC model).We assessed the ability of the 2014 ESC model to predict 30-day death after acute pulmonary embolism. Consecutive patients with symptomatic, confirmed pulmonary embolism included in prospective cohorts were merged in a collaborative database. Patients' risk was classified as high (shock or hypotension), intermediate-high (RVD and elevated troponin), intermediate-low (RVD or increased troponin or none) and low (sPESI 0). Study outcomes were death and pulmonary embolism-related death at 30 days.Among 906 patients (mean±sd age 68±16, 489 females), death and pulmonary embolism-related death occurred in 7.2% and 4.1%, respectively. Death rate was 22% in "high-risk" (95% CI 14.0-29.8), 7.7% in "intermediate-high-risk" (95% CI 4.5-10.9) and 6.0% in "intermediate-low-risk" patients (95% CI 3.4-8.6). One of the 196 "low-risk" patients died (0.5%, 95% CI 0-1.0; negative predictive value 99.5%).By using the 2014 ESC model, RVD or troponin tests would be avoided in about 20% of patients (sPESI 0), preserving a high negative predictive value. Risk stratification in patients at intermediate risk requires further improvement.

Contemporary anticoagulant treatment strategies in patients with acute pulmonary embolism at different risk for death.

INTRODUCTION: Availability of new treatment strategies for patients with acute pulmonary embolism (PE) have changed clinical practice with potential influence in short-term patients' outcomes. We aimed at assessing contemporary anticoagulation strategies and mortality in patients with acute PE included in the prospective, non-interventional, multicentre, COntemporary management of PE study. MATERIALS AND METHODS: Anticoagulant treatment at admission, during hospital-stay, at discharge and at 30-day are described in the overall population and by clinical severity. RESULTS: Overall, 5158 patients received anticoagulant treatment (99%); during the hospital-stay, 2298 received completely parenteral, 926 completely oral and 1934 parenteral followed by oral anticoagulation (1670 DOACs, 264 VKAs). Comorbidities and PE severity influenced the choice of in-hospital anticoagulation. The use of completely parenteral and completely oral anticoagulation varied based on PE severity. In patients treated with thrombolysis, DOACs were used in 46.4% and 80.1% during the hospital stay and at discharge, respectively. Death at 30 days occurred in 34.6% of patients not receiving anticoagulant treatment and in 1.5, 1.3, 3.4 and 8.1% of patients receiving completely oral, sequential with DOACs, sequential with VKAs and completely parenteral regimens, respectively. Increased mortality in patients receiving completely parenteral anticoagulation persisted after adjustment for PE severity. Completely oral anticoagulation was effective and safe also in patients at intermediate-high risk of death. CONCLUSIONS: Contemporary anticoagulation for acute PE includes parenteral agents in over 90% of patients; DOACs are used in the large majority of PE patients at discharge and their early use seems effective and safe also in selected intermediate-risk patients. TRIAL REGISTRATION NUMBER: NCT03631810.

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.

Adalimumab as a potential cause of drug-induced thrombocytopaenic microangiopathy.

We report the case of a 63-year-old male patient admitted to our emergency department for dyspnoea, peripheral oedema, severe diarrhoea and asthenia. History revealed Crohn's disease (CD) submitted to several intestinal surgical resections in the previous years. He recently started a treatment with adalimumab for the control of CD. Laboratory tests at the admission revealed severe haemolytic anaemia and thrombocytopaenia. Haptoglobin levels were low, schistocyte count was markedly increased. In the suspect of thrombotic microangiopathy, he was admitted to our internal medicine department where we urgently started plasma exchange (PEX). We observed normal ADAMTS-13 activity in absence of Shiga toxin or enterotoxic Escherichia c oli at stool tests. Despite a diagnosis of atypical haemolytic-uraemic syndrome, we observed full platelet count recovery and schistocytes normalisation after the fourth PEX. We then put a diagnosis of adalimumab-induced thrombocytopaenic microangiopathy. Adalimumab was withdrawn. We did not observe relapses in the following 3 months.

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.

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.

Definition of major bleeding: Prognostic classification.

BACKGROUND: In patients on anticoagulant treatment, the major bleeding (MB) definition released by the International Society of Thrombosis and Haemostasis (ISTH) is widely accepted. However, this definition identifies MBs with highly variable short-term risk of death. OBJECTIVES: The study aims were to derive and validate a classification of ISTH-defined MBs for the risk of short-term death. METHODS: Consecutive patients admitted for ISTH-defined MB occurring while on treatment with oral anticoagulants were included in the study and divided into a derivation and a validation cohort. Death within 30 days was the primary study outcome. RESULTS: Among 1077 patients with MB, 64/517 and 63/560 patients in the derivation and validation cohort died, respectively. In the derivation cohort, Glasgow coma scale (GCS) <14 and shock were predictors of death; critical site bleeding and hemoglobin decrease ≥2 g/dL, or transfusion ≥ 2 units were not. GCS <14 (hazard ratio [HR], 8.67; 95% confidence interval [CI], 3.93-19.13) was predictor of death in intracranial hemorrhage (ICH) and shock at admission (HR, 4.84; 95% CI, 2.01-11.70) and pericardial bleeding (HR, 11.37; 95% CI, 1.33-97.31) in non-ICH MBs. The predictive value of GCS <14 in ICH and shock and pericardial bleeding in non-ICH MBs was confirmed in the validation cohort. None of the patients with isolated ocular or articular bleeding died. A prognostic classification of ISTH-defined MBs for the risk of short-term death is proposed as "serious," "severe," and "life-threatening" (ICH with GCS <14 or non-ICH with shock) MBs. CONCLUSION: According to our study, ISTH-defined MBs can be stratified for the risk of death within 30 days.

Mortality in patients with intracerebral hemorrhage associated with antiplatelet agents, oral anticoagulants or no antithrombotic therapy.

The association between preceding treatment with antiplatelet agents (APs), vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) and mortality after intracerebral hemorrhage (ICH) remains unclear. The aim of this multicenter, prospective cohort study was to assess the risk for death after ICH in consecutive patients who were on treatment with APs, VKAs, DOACs, or no antithrombotic agent. The primary outcome was in-hospital death by day 30. ICH volume at admission and volume expansion were centrally assessed. Out of 598 study patients, in-hospital death occurred in 21% of patients who were on treatment with APs, 25% with VKAs, 30% with DOACs, and 13% with no antithrombotics. Crude death rate was higher in patients on antithrombotics as compared to patients receiving no antithrombotic agent. At multivariate analysis, age (HR 1.07; 95% CI 1.04-1.10), previous stroke (HR 1.83; 95% CI 1.14-2.93), GCS ≤8 at admission (HR 6.06; 95% CI 3.16-9.74) and GCS 9-12 (HR 3.38; 95% CI 1.81-6.33) were independent predictors of death. Treatment with APs (HR 1.29; 95% CI 0.61-2.76), VKAs (HR 1.42; 95% CI 0.70-2.88) or DOACs (HR 1.28; 95% CI 0.61-2.73) were not predictors of death in the overall study population, in non-trauma associated ICH as well as when GCS was not included in the model. ICH volume and volume expansion were independent predictors of death. In conclusion, preceding treatment with antithrombotic is associated with the severity of ICH. Age, previous stroke and clinical severity at presentation were independent predictors of in-hospital death in patients with ICH.

Prophylaxis of Venous Thromboembolism after Hospital Discharge in Internal Medicine: Findings from the Observational FADOI-NoTEVole Study.

BACKGROUND AND AIM: Post-discharge prophylaxis for venous thromboembolism (VTE) is a challenging issue in patients hospitalised in Internal Medicine Units (IMUs). The aim of this study was to evaluate the frequency and the factors associated with post-discharge prophylaxis for VTE in IMUs. METHODS: Multi-centre, retrospective study including consecutive patients who were admitted for any cause and discharged from an IMU. RESULTS: Overall, 3,740 patients (mean age 74.1 ± 15.7 years) were included in the study at 38 IMUs in Italy. At discharge, the percentage of patients receiving pharmacological thromboprophylaxis was 16.0% (20.1% after excluding patients treated with anticoagulants for indications other than VTE prophylaxis). At multivariable analysis, history of ischaemic stroke, hypomobility ≥ 7 days, central venous catheter, ≥ 10 versus ≤ 5 days of hospital stay, use of corticosteroids, cancer, history of falls, availability of a caregiver, infections and age were significantly associated with thromboprophylaxis, while an inverse correlation was observed with concomitant anti-platelet drugs and platelet count < 70,000/mm3. Patients with a Padua Prediction Score ≥ 4 versus < 4 and with an IMPROVE bleeding score ≥ 7 versus < 7 more frequently received prophylaxis at discharge (31.2% vs. 10.6%, p < 0.0001, and 25.7% vs. 19.6%, p = 0.028, respectively). CONCLUSION: In this study, one in five patients discharged from an Italian IMU received prophylaxis for VTE. The perceived thrombotic risk is significantly related to the use of prophylaxis.

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.

Major bleeding with vitamin K antagonists or direct oral anticoagulants in real-life.

BACKGROUND: Limited data are available on major bleeding (MB) occurring during treatment with vitamin K (VKAs) or direct oral anticoagulants (DOACs) outside clinical trials. METHODS: Patients hospitalized for MB while on treatment with VKAs or DOACs were included in a multicenter study to compare clinical presentation, management and outcome of bleeding. The primary study outcome was death at 30days. RESULTS: Between September 2013 and September 2015, 806 patients were included in the study, 76% on VKAs and 24% on DOACs. MB was an intracranial hemorrhage in 51% and 21% patients on VKAs or DOACs, respectively (Odds Ratio [OR] 3.79; 95% confidence interval [CI] 2.59-5.54) a gastrointestinal bleeding in 46% and 25% patients on DOACs and VKAs, respectively (OR 2.62; 95% CI 1.87-3.68). Death at 30days occurred in 130 patients (16%), 18% and 9% of VKA and DOAC patients (HR 1.95; 95% CI 1.19-3.22, p=0.008). The rate of death at 30days was similar in VKA and DOAC patients with intracranial hemorrhage (26% and 24%; HR 1.05, 95% CI 0.54-2.02) and gastrointestinal bleeding (11% and 7%; HR 1.46, 95% CI 0.57-3.74) and higher in VKA than DOAC patients with other MBs (10% and 3%; HR 3.42, 95% CI 0.78-15.03). CONCLUSIONS: Admission for ICH is less frequent for DOAC patients compared with VKA patients. Admission for gastrointestinal MB is more frequent for DOAC as compared to VKA patients. Mortality seems lower in patients with MBs while on DOACs than VKAs but this finding varies across different types of MBs.

Neural hypernetwork approach for pulmonary embolism diagnosis.

BACKGROUND: Hypernetworks are based on topological simplicial complexes and generalize the concept of two-body relation to many-body relation. Furthermore, Hypernetworks provide a significant generalization of network theory, enabling the integration of relational structure, logic and analytic dynamics. A pulmonary embolism is a blockage of the main artery of the lung or one of its branches, frequently fatal. RESULTS: Our study uses data on 28 diagnostic features of 1427 people considered to be at risk of pulmonary embolism enrolled in the Department of Internal and Subintensive Medicine of an Italian National Hospital "Ospedali Riuniti di Ancona". Patients arrived in the department after a first screening executed by the emergency room. The resulting neural hypernetwork correctly recognized 94% of those developing pulmonary embolism. This is better than previous results obtained with other methods (statistical selection of features, partial least squares regression, topological data analysis in a metric space). CONCLUSION: In this work we successfully derived a new integrative approach for the analysis of partial and incomplete datasets that is based on Q-analysis with machine learning. The new approach, called Neural Hypernetwork, has been applied to a case study of pulmonary embolism diagnosis. The novelty of this method is that it does not use clinical parameters extracted by imaging analysis.