The Intensive Care Global Study on Severe Acute Respiratory Infection (IC-GLOSSARI): a Multicenter, Multinational, 14-Day Inception Cohort Study

PURPOSE: In this prospective, multicenter, 14-day inception cohort study, we investigated the epidemiology, patterns of infections, and outcome in patients admitted to the intensive care unit (ICU) as a result of severe acute respiratory infections (SARIs). METHODS: All patients admitted to one of 206 participating ICUs during two study weeks, one in November 2013 and the other in January 2014, were screened. SARI was defined as possible, probable, or microbiologically confirmed respiratory tract infection with recent onset dyspnea and/or fever. The primary outcome parameter was in-hospital mortality within 60 days of admission to the ICU. RESULTS: Among the 5550 patients admitted during the study periods, 663 (11.9 %) had SARI. On admission to the ICU, Gram-positive and Gram-negative bacteria were found in 29.6 and 26.2 % of SARI patients but rarely atypical bacteria (1.0 %); viruses were present in 7.7 % of patients. Organ failure occurred in 74.7 % of patients in the ICU, mostly respiratory (53.8 %), cardiovascular (44.5 %), and renal (44.6 %). ICU and in-hospital mortality rates in patients with SARI were 20.2 and 27.2 %, respectively. In multivariable analysis, older age, greater severity scores at ICU admission, and hematologic malignancy or liver disease were independently associated with an increased risk of in-hospital death, whereas influenza vaccination prior to ICU admission and adequate antibiotic administration on ICU admission were associated with a lower risk. CONCLUSIONS: Admission to the ICU for SARI is common and associated with high morbidity and mortality rates. We identified several risk factors for in-hospital death that may be useful for risk stratification in these patients.

Polymerase Chain Reaction Screening for Fungemia and/or Invasive Fungal Infections in Patients with Hematologic Malignancies

INTRODUCTION: Invasive fungal infections (IFIs) are a life-threatening complication in patients with hematologic malignancies, mainly in acute leukemia patients, following chemotherapy. IFI incidence is increasing, and associated mortality remains high due to unreliable diagnosis. Antifungal drugs are often limited by inadequate antimicrobial spectrum and side effects. Thus, the detection of circulating fungal DNA has been advocated as a rapid, more sensitive diagnostic tool. PATIENTS AND METHODS: Between June 01 and January 03, weekly blood samples (1,311) were screened from 193 patients undergoing intensive myelosuppressive or immunosuppressive therapy. IFI cases were classified according to European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Fungal DNA was extracted from whole blood and amplified using polymerase chain reaction (PCR) published primers that bind to the conserved regions of the fungal 18S rRNA gene sequence. In our study, two or more consecutive positive samples were always associated with fungal disease. RESULTS: PCR screening predicted the development of IFI to be 17 days (median). This test had a specificity of 91.1% and a sensitivity of 75%. IFI incidence was 7.8%. DISCUSSION: Therefore, our results confirm the potential usefulness of PCR serial screening and the clinical applicability in everyday routine. PCR screening offers a noninvasive repeatable aid to the diagnosis of IFI.

Severe Isolated Thrombocytopenia After Clopidogrel and Pentoxifylline Therapy: a Case Report

INTRODUCTION: Clopidogrel is frequently associated with thrombotic thrombocytopenic purpura, however this drug is rarely related to severe isolated thrombocytopenia. Pentoxifylline has previously been associated with thrombocytopenia only once. To the best of our knowledge, this is the first report of severe isolated thrombocytopenia after therapy with both clopidogrel and pentoxyfilline. CASE PRESENTATION: We report the case of a 79-year-old Caucasian man who presented to our facility with intermittent claudication. He had obliterative arterial disease and started therapy with clopidogrel and pentoxifylline. His basal platelet count was 194 × 109 cells/L. At three days after the start of treatment, our patient had lower limb petechia and stopped taking clopidogrel and pentoxifylline. His platelet count lowered to 4 × 109 cells/L and our patient was admitted to hospital. Our patient had purpura with no other hemorrhages or splenomegaly. Results of a blood smear were normal, and a bone marrow study showed dysmegakaryopoiesis. Antiplatelet antibody test results were negative, as were all viral serology tests. Imaging study results were normal. Our patient was given immunoglobulin but there was no sustained platelet increase, so corticotherapy was started as the next treatment step. At five months after clopidogrel and pentoxifylline were discontinued, his platelet count continued increasing even after prednisolone was tapered. CONCLUSIONS: Severe isolated thrombocytopenia may appear as a side effect when using clopidogrel and pentoxifylline. These drugs are widely used by general physicians, internists, cardiologists and vascular surgeons. We hope this report will raise awareness of the need to monitor the platelet count in patients taking these drugs.

Terapêutica Trombolítica no Enfarte Agudo do Miocárdio: Motivos de Inelegibilidade

STUDY OBJECTIVE: to establish the reasons of ineligibility for thrombolytic therapy (TL) in a group of patients with acute myocardial infarction (AMI). DESIGN: retrospective analysis of protocols and clinical records. SETTING: the medical intensive care unit (ICU) of a tertiary care hospital. PATIENTS AND METHODS: we studied the records from patients with AMI admitted to the ICU during a five-year period (1987-91) and excluded from TL, to determine the cause(s) of ineligibility. RESULTS: we found 1669 patients with AMI, 89 of which were excluded from the study. Of the remaining 1580 patients, 1274 (80.6%) did not receive TL. Mean age was 64.4 years; 66.4% were men. Mortality was 24.6%. Mean duration of chest pain was 19.4 hours. Chief reasons for exclusion from TL were advanced age (43.1% of patients) and delayed presentation (55.7%); one of these was present in 79.2%. CONCLUSIONS: this study confirmed the high mortality of patients with AMI who do not receive TL. Advanced age and delayed presentation were the main causes of ineligibility. As age is being abandoned as an exclusion criterion, efforts for expansion of TL should center on the earlier arrival of patients to centers where it is available.

Routine Transthoracic Echocardiography in a General Intensive Care Unit: an 18 Month Survey in 704 Patients

The authors analyzed 704 transthoracic echocardiographic (TTE) examinations, performed routinely to all admitted patients to a general 16-bed Intensive Care Unit (ICU) during an 18-month period. Data acquisition and prevalence of abnormalities of cardiac structures and function were assessed, as well as the new, previously unknown severe diagnoses. A TTE was performed within the first 24 h of admission on 704 consecutive patients, with a mean age of 61.5+/-17.5 years, ICU stay of 10.6+/-17.1 days, APACHE II 22.6+/-8.9, and SAPS II 52.7+/-20.4. In four patients, TTE could not be performed. Left ventricular (LV) dimensions were quantified in 689 (97.8%) patients, and LV function in 670 (95.2%) patients. Cardiac output (CO) was determined in 610 (86.7%), and mitral E/A in 399 (85.9% of patients in sinus rhythm). Echocardiographic abnormalities were detected in 234 (33%) patients, the most common being left atrial (LA) enlargement (n=163), and LV dysfunction (n=132). Patients with these alterations were older (66+/-16.5 vs 58.1+/-17.4, p<0.001), presented a higher APACHE II score (24.4+/-8.7 vs 21.1+/-8.9, p<0.001), and had a higher mortality rate (40.1% vs 25.4%, p<0.001). Severe, previously unknown echocardiographic diagnoses were detected in 53 (7.5%) patients; the most frequent condition was severe LV dysfunction. Through a multivariate logistic regression analysis, it was determined that mortality was affected by tricuspid regurgitation (p=0.016, CI 1.007-1.016) and ICU stay (p<0.001, CI 1-1.019). We conclude that TTE can detect most cardiac structures in a general ICU. One-third of the patients studied presented cardiac structural or functional alterations and 7.5% severe previously unknown diagnoses.

Mesenchymal Stem Cell Therapy in Heart Disease

Cardiovascular disease is among the main causes of mortality and morbidity worldwide. Despite significant advances in medical and interventional therapy, the prognosis of conditions such as ischemic heart disease is still dismal. There is thus a need to investigate new therapeutic tools, one of which is stem cell therapy. Hematopoietic stem cells are the most studied type, and the fact that their biology is relatively well understood has led to their being used in preclinical research and clinical trials. However, the results of some of these studies have been controversial, which has opened the way for studies on other cell types, such as mesenchymal stem cells. These cells have immunomodulatory properties which suggest that they have therapeutic potential in cardiology. In the present article, the authors review the state of the art regarding mesenchymal stem cells, from basic and translational research to their use in clinical trials on ischemic heart disease, heart failure and arrhythmias, and discuss possible future uses.

Mortality after Discharge from Intensive Care: the Impact of Organ System Failure and Nursing Workload Use at Discharge

OBJECTIVES: Mortality after ICU discharge accounts for approx. 20-30% of deaths. We examined whether post-ICU discharge mortality is associated with the presence and severity of organ dysfunction/failure just before ICU discharge. PATIENTS AND METHODS: The study used the database of the EURICUS-II study, with a total of 4,621 patients, including 2,958 discharged alive to the general wards (post-ICU mortality 8.6%). Over a 4-month period we collected clinical and demographic characteristics, including the Simplified Acute Physiology Score (SAPS II), Nine Equivalents of Nursing Manpower Use Score, and Sequential Organ Failure Assessment (SOFA) score. RESULTS: Those who died in the hospital after ICU discharge had a higher SAPS II score, were more frequently nonoperative, admitted from the ward, and had stayed longer in the ICU. Their degree of organ dysfunction/failure was higher (admission, maximum, and delta SOFA scores). They required more nursing workload resources while in the ICU. Both the amount of organ dysfunction/failure (especially cardiovascular, neurological, renal, and respiratory) and the amount of nursing workload that they required on the day before discharge were higher. The presence of residual CNS and renal dysfunction/failure were especially prognostic factors at ICU discharge. Multivariate analysis showed only predischarge organ dysfunction/failure to be important; thus the increased use of nursing workload resources before discharge probably reflects only the underlying organ dysfunction/failure. CONCLUSIONS: It is better to delay the discharge of a patient with organ dysfunction/failure from the ICU, unless adequate monitoring and therapeutic resources are available in the ward.

Inferior Vena Cava Filter Placement During Pregnancy: an Adjuvant Option When Medical Therapy Fails

The authors present a case of a 27-year-old multiparous woman, with multiple thrombophilia, whose pregnancy was complicated with deep venous thrombosis requiring placement of a vena cava filter. At 15th week of gestation, following an acute deep venous thrombosis of the right inferior limb, anticoagulant therapy with low-molecular-weight heparin (LMWH) was instituted without improvement in her clinical status. Subsequently, at 18 weeks of pregnancy, LMWH was switched to warfarin. At 30th week of gestation, the maintenance of high thrombotic risk was the premise for placement of an inferior vena cava filter for prophylaxis of pulmonary embolism during childbirth and postpartum. There were no complications and a vaginal delivery was accomplished at 37 weeks of gestation. Venal placement of inferior vena cava filters is an attractive option as prophylaxis for pulmonary embolism during pregnancy.

Modeling in-Hospital Patient Survival During the First 28 Days After Intensive Care Unit Admission: a Prognostic Model for Clinical Trials in General Critically Ill Patients

OBJECTIVE: The objective of the study was to develop a model for estimating patient 28-day in-hospital mortality using 2 different statistical approaches. DESIGN: The study was designed to develop an outcome prediction model for 28-day in-hospital mortality using (a) logistic regression with random effects and (b) a multilevel Cox proportional hazards model. SETTING: The study involved 305 intensive care units (ICUs) from the basic Simplified Acute Physiology Score (SAPS) 3 cohort. PATIENTS AND PARTICIPANTS: Patients (n = 17138) were from the SAPS 3 database with follow-up data pertaining to the first 28 days in hospital after ICU admission. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The database was divided randomly into 5 roughly equal-sized parts (at the ICU level). It was thus possible to run the model-building procedure 5 times, each time taking four fifths of the sample as a development set and the remaining fifth as the validation set. At 28 days after ICU admission, 19.98% of the patients were still in the hospital. Because of the different sampling space and outcome variables, both models presented a better fit in this sample than did the SAPS 3 admission score calibrated to vital status at hospital discharge, both on the general population and in major subgroups. CONCLUSIONS: Both statistical methods can be used to model the 28-day in-hospital mortality better than the SAPS 3 admission model. However, because the logistic regression approach is specifically designed to forecast 28-day mortality, and given the high uncertainty associated with the assumption of the proportionality of risks in the Cox model, the logistic regression approach proved to be superior.

Characterizing the Risk Profiles of Intensive Care Units

OBJECTIVE: To develop a new method to evaluate the performance of individual ICUs through the calculation and visualisation of risk profiles. METHODS: The study included 102,561 patients consecutively admitted to 77 ICUs in Austria. We customized the function which predicts hospital mortality (using SAPS II) for each ICU. We then compared the risks of hospital mortality resulting from this function with the risks which would be obtained using the original function. The derived risk ratio was then plotted together with point-wise confidence intervals in order to visualise the individual risk profile of each ICU over the whole spectrum of expected hospital mortality. MAIN MEASUREMENTS AND RESULTS: We calculated risk profiles for all ICUs in the ASDI data set according to the proposed method. We show examples how the clinical performance of ICUs may depend on the severity of illness of their patients. Both the distribution of the Hosmer-Lemeshow goodness-of-fit test statistics and the histogram of the corresponding P values demonstrated a good fit of the individual risk models. CONCLUSIONS: Our risk profile model makes it possible to evaluate ICUs on the basis of the specific risk for patients to die compared to a reference sample over the whole spectrum of hospital mortality. Thus, ICUs at different levels of severity of illness can be directly compared, giving a clear advantage over the use of the conventional single point estimate of the overall observed-to-expected mortality ratio.

Zinc Therapy of Neurological Wilson's Disease in a Woman with Two Foetus with Agenesis of the Corpus Callosum

8A>C>86A G:EDGI: A patient diagnosed Wilson’s disease (WD) 22 years previously, successfully treated initially with zinc, developed neuropsychiatric disease after years of irregular therapy. Reassuming zinc therapy was successful. After a normal pregnancy, she had two therapeutic abortions for corpus callosum agenesis, and a missed abortion. We review the genetics, physiopathology, clinics and imagiologic response to zinc therapy, the problems of pregnancy in WD, advising to maintain therapy. A hypothetic cause for fetus brain anomaly would be hypocupremia due to zinc therapy, confronting with two other possibilities, one related to Wilson’s disease in itself, other due to a congenital syndrome of agenesis of the corpus callosum, impossible to diagnose by our available diagnostic methods.

Long-Term Evaluation of Recurrence after Photodynamic Therapy with Topical Methyl Aminolevulinate for Non-Melanoma Skin Cancer: a Hospital-Based Study

Introduction & Objectives: Several factors may influence the decision to pursue nonsurgical modalities for the treatment of non-melanoma skin cancer. Topical photodynamic therapy (PDT) is a non-invasive alternative treatment reported to have a high efficacy when using standardized protocols in Bowen’s disease (BD), superficial basal cell carcinoma (BCC) and in thin nodular BCC. However, long-term recurrence studies are lacking. The aim of this study was to evaluate the long-term efficacy of PDT with topical methylaminolevulinate (MAL) for the treatment of BD and BCC in a dermato-oncology department. Materials & Methods: All patients with the diagnosis of BD or BCC, treated with MAL-PDT from the years 2004 to 2008, were enrolled. Treatment protocol included two MAL-PDT sessions one week apart repeated at three months when incomplete response, using a red light dose of 37-40 J/cm2 and an exposure time of 8’20’’. Clinical records were retrospectively reviewed, and data regarding age, sex, tumour location, size, treatment outcomes and recurrence were registered. Descriptive analysis was performed using chi square tests, followed by survival analysis with the Kaplan-Meier and Cox regression models. Results: Sixty-eight patients (median age 71.0 years, P25;P75=30;92) with a total of 78 tumours (31 BD, 45 superficial BCC, 2 nodular BCC) and a median tumour size of 5 cm2 were treated. Overall, the median follow-up period was 43.5 months (P25;P75=0;100), and a total recurrence rate of 33.8% was observed (24.4 % for BCC vs. 45.2% for BD). Estimated recurrence rates for BCC and BD were 5.0% vs. 7.4% at 6 months, 23.4% vs. 27.9% at 12 months, and 30.0% vs. 72.4% at 60 months. Both age and diagnosis were independent prognostic factors for recurrence, with significantly higher estimated recurrence rates in patients with BD (p=0.0036) or younger than 58 years old (p=0.039). The risk of recurrence (hazard ratio) was 2.4 times higher in patients with BD compared to superficial BCC (95% CI:1.1-5.3; p=0.033), and 2.8 times higher in patients younger than 58 years old (95% CI:1.2-6.5; p=0.02). Conclusions: In the studied population, estimated recurrence rates are higher than those expected from available literature, possibly due to a longer follow-up period. To the authors’ knowledge there is only one other study with a similar follow-up period, regarding BCC solely. BD, as an in situ squamous cell carcinoma, has a higher tendency to recur than superficial BCC. Despite greater cosmesis, PDT might no be the best treatment option for young patients considering their higher risk of recurrence.

Vulvar Lichen Sclerosus: Efficacy of Photodynamic Therapy Under Conscious Sedation with Inhaled 50% Nitrous Oxide and Oxygen Mixture

Anogenital lichen sclerosus is a chronic, inflammatory, mucocutaneous disorder of significant morbidity. Common symptoms include pruritus, pain, dysuria, and dyspareunia, frequently of difficult control. Photodynamic therapy (PDT) may be an effective therapeutic option in selected cases refractory to first--‐line treatment options. However, procedure--‐related pain is a limiting factor in patient adherence to treatment. Conscious sedation and analgesia with a ready--‐to--‐use gas mixture of nitrous oxide and oxygen is useful in short--‐term procedures. It provides a rapid, effective, and short--‐lived effect, without the need for anesthesiology support. A 75--‐year--‐old woman presented with a highly symptomatic, histologically confirmed vulvar lichen sclerosus, with at least 15 years of evolution. Pain, pruritus, and dysuria were intense and disabling. Treatment with ultrapotent topical corticosteroids proved to be ineffective despite patient compliance. She was then referred for PDT. A total of 3 sessions were performed, held at a mean interval of 9 weeks, and under the analgesic and sedative effect of nitrous oxide/oxygen gas. Response to treatment was evaluated through a daily, self--‐reported pain rating scale. Dysuria remitted completely after the first PDT session. An 80% reduction in pruritus and pain was observed after the third session, and has been sustained for the past six months without further need for topical corticotherapy. Treatment sessions were well tolerated and pain-- free, with no side effects to report. PDT appears to be effective in the symptomatic treatment of vulvar lichen sclerosus. To the authors’ knowledge this is the first case reporting the use of inhaled nitrous oxide/oxygen gas mixture during PDT performed in the genital area. Its analgesic and sedative effects may increase patients’ adherence to this painful procedure. Furthermore, given its safety, it can be easily managed in outpatient clinics by trained dermatologists.

Renal Replacement Therapy in Critically Ill Patients - What Modality Should We Choose?

A lesão renal aguda é uma complicação comum nas unidades de cuidados intensivos. A mortalidade do doente crítico que requer diálise é extremamente elevada, apesar dos avanços significativos dos cuidados prestados a estes doentes. Há várias décadas que se discute o tipo de modalidade dialítica a oferecer a estes doentes (continua ou intermitente) e os principais fatores que pesam na decisão clínica são os meios e a experiência do centro, bem como a condição clínica do doente. Vários estudos tentaram estabelecer a melhor abordagem ao doente crítico com lesão renal aguda e necessidade dialítica, em termos de sobrevida do doente e recuperação renal. Nesta revisão tentarei resumir as evidências disponíveis sobre este tema.