Alexandre de Matos Soeiro

PoSt-mortEm hIStoLogICAL PuLmoNAry ANALySIS IN PAtIENtS wIth hIV/AIDS

OBJECTIVES Certain aspects of pulmonary pathology observed in autopsies of HIV/AIDS patients are still unknown. This study considers 250 autopsies of HIV/AIDS patients who died of acute respiratory failure and describes the demographic data, etiology, and histological pulmonary findings of the various pathologies. METHODS The following data were obtained: age, sex, and major associated diseases (found at the autopsy). Pulmonary histopathology was categorized as: diffuse alveolar damage; pulmonary edema; alveolar hemorrhage; and acute interstitial pneumonia. Odds ratio of the HIV/AIDS-associated diseases developing a specific histopathological pattern was determined by logistic regression. RESULTS A total of 197 men and 53 women were studied. The mean age was 36 years. Bacterial bronchopneumonia was present in 36% (91 cases) and Pneumocystis jiroveci pneumonia in 27% (68) of patients. Pulmonary histopathology showed acute interstitial pneumonia in 40% (99), diffuse alveolar damage in 36% (89), pulmonary edema in 13% (33), and alveolar hemorrhage in 12% (29) of patients. Multivariate analysis showed a significant and positive association between Pneumocystis jiroveci pneumonia and acute interstitial pneumonia (Odds ratio, 4.51; 95% CI, 2.46 – 8.24; p < 0.001), severe sepsis and/or septic shock and diffuse alveolar damage (Odds ratio, 3.60; 95% CI, 1.78 –7.27; p < 0.001), and cytomegalovirus and acute interstitial pneumonia (Odds ratio, 2.22; 95% CI, 1.01 – 4.93; p = 0.05). CONCLUSIONS This report is the first autopsy study to include demographic data, etiologic diagnosis, and respective histopathological findings in patients with HIV/AIDS and acute respiratory failure. Further studies are necessary to elucidate the complete pulmonary physiopathological mechanism involved with each HIV/AIDS-associated disease.

Semiquantitative assessment of surgical lung biopsy: predictive value and impact on survival of patients with diffuse pulmonary infiltrate

PURPOSE Surgical lung biopsy has been studied in distinct populations, mostly going beyond clinical issues to impinge upon routine histopathological diagnostic information in diffuse infiltrates; however, detailed tissue analyses have rarely been performed. The present study was designed to investigate the prognostic contribution provided by detailed tissue analysis in diffuse infiltrates. METHODS Medical records and surgical lung biopsies from the period of 1982 to 2003 of 63 patients older than 18 years with diffuse infiltrates were retrospectively examined. Lung parenchyma was histologically divided into 4 anatomical compartments: interstitium, airways, vessels, and alveolar spaces. Histological changes throughout these anatomical compartments were then evaluated according to their acute or chronic evolutional character. A semiquantitative scoring system was applied to histologic findings to evaluate the intensity and extent of the pathological process. We applied logistic regression to predict the risk of death associated with acute and chronic histological changes and to estimate the odds ratios for each of the independent variables in the model. RESULTS Impact on survival was found for male gender (P = 0.03), presence of diffuse alveolar damage (P = 0.001), and chronic histological changes (P = 0.0004) on biopsy. Thus, being male was associated with a slightly lower risk (O.R. = 0.18; P=0.03) of dying than being female. Death risk was increased 17 times in the presence of acute histological changes such as diffuse alveolar damage and 2.5 times in the presence of chronic histological changes. CONCLUSION Detailed analysis of histological specimens can provide more than a nosological diagnosis: this approach can provide valuable information concerning prognosis.

[Cardiovascular events: a class effect by COX-2 inhibitors].

Non-steroidal anti-inflamatories (NSAIDs) are widely used in the treatment of post-surgery pain1, osteoarthritis2, rheumatoid arthritis3 and muscle-skeletal pain4,5, in different conditions. Major effects are: anti-inflammatory, analgesic, and antipyretic6. Generally speaking, such effects are associated to the inhibition of the enzyme cyclooxygenase (COX). COX catalyzes the transformation of arachidonic acid into different lipid mediators called prostaglandins and thromboxanes2. Those substances play a relevant hemostatic role in protecting gastric mucosa, renal physiology, and platelet aggregation, in addition to having their production induced under conditions such as inflammation and cancer7. Two isozymes – or forms of the COX enzyme – have been characterized: cyclooxygenase-1 (COX-1) and cycloxygenase-2(COX-2)2. COX-1 has shown to be constitutive in all body tissues8. It is the only isozyme found in platelets, leading to the formation of TXA2. It is found in gastric mucosa, among other tissues, where it catalyzes the biosynthesis of cytoprotective prostaglandins in vascular endotelium and in renal tissue. Finally, it is believed that COX-1 also plays a role in pathologic conditions such as inflammation7. On the other hand, COX-2 is shown to be increased in inflammatory and cell transformation processes particularly9-12, although its constitutive expression has been demonstrated in some CNS and kidney tissues7.

Skeletonized coronary arteries: pathophysiological and clinical aspects of vascular calcification

The role of calcification in coronary artery disease is gaining importance, both in research studies and in clinical application. Calcified plaque has long been considered to be the most important atherosclerotic plaque within the arterial tree and frequently presents a challenge for percutaneous intervention. Current investigations have shown that plaque calcification has a dynamic course that is closely related to the magnitude of vascular inflammation. Numerous inflammatory factors synthesized during the early stages of atherosclerosis induce the expression and activation of osteoblast-like cells localized in the arterial wall that produce calcium. There is no doubt that the role of these factors in calcification associated with coronary artery disease could be a crucial strategic point in prevention and treatment. A number of diagnostic imaging methods have been developed in recent years, but their performance needs to be improved. In this context, we undertook an update on coronary calcification, focusing on physiopathology, clinical implications, and imaging techniques.

Demographic, etiological, and histological pulmonary analysis of patients with acute respiratory failure: a study of 19 years of autopsies

INTRODUCTION: Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown. OBJECTIVES: The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure. METHOD: Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases. The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia. The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression. RESULTS: Bacterial bronchopneumonia was present in 33.9% of the cases and cancer in 28.1%. The pulmonary histopathology showed diffuse alveolar damage in 40.7% (1,917) of the cases. A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/AIDS and liver cirrhosis. CONCLUSIONS: Bronchopneumonia was the most common diagnosis in these cases. The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions. Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure.

Surgical myocardial revascularization of patients with ischemic cardiomyopathy and severe left ventricular disfunction

OBJECTIVE To determine long-term survival, identify preoperative factors predictive of a favorable outcome, and assess functional improvement after coronary artery bypass grafting in patients with advanced left ventricular dysfunction. METHODS Between 1995 and 2001, 244 patients who underwent coronary artery bypass grafting and had a preoperative left ventricular ejection fraction less than or equal to 35% were included. left ventricular ejection fraction was determined by uniplanar or biplanar ventriculography during left heart catheterization. Indication for surgery was predominance of tissue viability. Functional improvement was evaluated through echocardiography and gated scintigraphy at exercise/rest. Survival was determined by Kaplan-Meier analysis. RESULTS Mean left ventricular ejection fraction was 29+/-4% (ranged from 9% to 35%). An average of 3.01 coronary bypass grafts per patient were performed. In-hospital mortality was 3.7% (9 patients). The 4-year survival rate was 89.7%. Multivariate correlates of favorable short- and long-term outcome were preoperative New York Heart Association Funcional classification for congestive heart failure class I/II, lower PAsP, higher left ventricular ejection fraction and gated left ventricular ejection fraction Ex/Rest ratio >5%. Left ventricular ejection fraction rise from 32+/-5% to 39+/-5%, p <0.001. Gated left ventricular ejection fraction at exercise/rest increased markedly after surgery: from 27+/-8%/23+/-7% to 37+/-5%/31+/-6%, p <0.001. CONCLUSIONS In selected patients with severe ischemic left ventricular dysfunction and predominance of tissue viability, coronary artery bypass grafting may be capable of implement preoperative clinical/functional parameters in predicting outcome as left ventricular ejection fraction and gated left ventricular ejection fraction at exercise/rest.

Alterações histopatológicas pulmonares em pacientes com insuficiência respiratória aguda: um estudo em autopsias

OBJECTIVE: To present the pulmonary histopathological alterations found in the autopsies of patients with acute respiratory failure (ARF) and determine whether underlying diseases and certain associated risk factors increase the incidence of these histopathological patterns. METHODS: Final autopsy reports were reviewed, and 3030 autopsies of patients > 1 year of age with an underlying disease and associated risk factors were selected. All had developed diffuse infiltrates and died of ARF-related pulmonary alterations. RESULTS: The principal pulmonary histopathological alterations resulting in immediate death were diffuse alveolar damage (DAD), pulmonary edema, lymphocytic interstitial pneumonia (LIP) and alveolar hemorrhage. The principal underlying diseases were AIDS, bronchopneumonia, sepsis, liver cirrhosis, pulmonary thromboembolism, acute myocardial infarction (AMI), cerebrovascular accident, tuberculosis, cancer, chronic kidney failure and leukemia. The principal associated risk factors were as follows: age > 50 years; arterial hypertension; congestive heart failure; chronic obstructive pulmonary disease; and diabetes mellitus. These risk factors and AIDS correlated with a high risk of developing LIP; these same risk factors, if concomitant with sepsis or liver cirrhosis, correlated with a risk of developing DAD; thromboembolism and these risk factors correlated with a risk of developing alveolar hemorrhage; these risk factors and AMI correlated with a risk of developing pulmonary edema. CONCLUSION: Pulmonary findings in patients who died of ARF presented four histopathological patterns: DAD, pulmonary edema, LIP and alveolar hemorrhage. Underlying diseases and certain associated risk factors correlated positively with specific histopathological findings on autopsy.

Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study

Background: Acute aortic syndromes (AASs) are rare and severe cardiovascular emergencies with unspecific symptoms. For AASs, both misdiagnosis and overtesting are key concerns, and standardized diagnostic strategies may help physicians to balance these risks. D-dimer (DD) is highly sensitive for AAS but is inadequate as a stand-alone test. Integration of pretest probability assessment with DD testing is feasible, but the safety and efficiency of such a diagnostic strategy are currently unknown. Methods: In a multicenter prospective observational study involving 6 hospitals in 4 countries from 2014 to 2016, consecutive outpatients were eligible if they had ≥1 of the following: chest/abdominal/back pain, syncope, perfusion deficit, and if AAS was in the differential diagnosis. The tool for pretest probability assessment was the aortic dissection detection risk score (ADD-RS, 0–3) per current guidelines. DD was considered negative (DD−) if <500 ng/mL. Final case adjudication was based on conclusive diagnostic imaging, autopsy, surgery, or 14-day follow-up. Outcomes were the failure rate and efficiency of a diagnostic strategy for ruling out AAS in patients with ADD-RS=0/DD− or ADD-RS ⩽1/DD−. Results: A total of 1850 patients were analyzed. Of these, 438 patients (24%) had ADD-RS=0, 1071 patients (58%) had ADD-RS=1, and 341 patients (18%) had ADD-RS >1. Two hundred forty-one patients (13%) had AAS: 125 had type A aortic dissection, 53 had type B aortic dissection, 35 had intramural aortic hematoma, 18 had aortic rupture, and 10 had penetrating aortic ulcer. A positive DD test result had an overall sensitivity of 96.7% (95% confidence interval [CI], 93.6–98.6) and a specificity of 64% (95% CI, 61.6–66.4) for the diagnosis of AAS; 8 patients with AAS had DD−. In 294 patients with ADD-RS=0/DD−, 1 case of AAS was observed. This yielded a failure rate of 0.3% (95% CI, 0.1–1.9) and an efficiency of 15.9% (95% CI, 14.3–17.6) for the ADD-RS=0/DD− strategy. In 924 patients with ADD-RS ⩽1/DD−, 3 cases of AAS were observed. This yielded a failure rate of 0.3% (95% CI, 0.1–1) and an efficiency of 49.9% (95% CI, 47.7–52.2) for the ADD-RS ⩽1/DD− strategy. Conclusions: Integration of ADD-RS (either ADD-RS=0 or ADD-RS ⩽1) with DD may be considered to standardize diagnostic rule out of AAS. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02086136.

Correlation between surgical lung biopsy and autopsy findings and clinical data in patients with diffuse pulmonary infiltrates and acute respiratory failure

INTRODUCTION Surgical lung biopsy is an invasive procedure performed when other procedures have failed to provide an urgent and specific diagnosis, but there may be reluctance to perform it in critically ill patients with diffuse pulmonary infiltrates. PURPOSE To evaluate the diagnostic accuracy, the changes in therapy and survival of patients with diffuse lung infiltrates, mostly presenting acute respiratory failure, who underwent surgical biopsy. METHODS We retrospectively examined medical records and surgical lung biopsies from 1982 to 2003 of 63 patients older than 18 years with diffuse infiltrates. Clinical diagnoses were compared to histopathological ones, from biopsies and autopsies. Laboratory and epidemiological data were evaluated, and their relationship to hospital survival was analyzed. RESULTS All histological specimens exhibited abnormalities, mostly presenting benign/inflammatory etiologies. Fifteen patients had an etiologic factor determined in biopsy, most commonly Mycobacterium tuberculosis. The preoperative diagnosis was rectified in 37 patients. Autopsies were obtained in 25 patients and confirmed biopsy results in 72% of cases. Therapy was changed for 65% of patients based on biopsy results. Forty-nine percent of patients survived to be discharged from the hospital. Characteristics that differed significantly between survivors and nonsurvivors included sex (P = 0.05), presence of comorbidity (P = 0.05), SpO2 (P = 0.05), and presence of diffuse alveolar damage in the biopsy (P = 0.004). CONCLUSION Surgical lung biopsy provided a specific, accurate etiologic diagnosis in many patients with diffuse pulmonary infiltrates when clinical improvement did not occur after standard treatment. Surgical lung biopsy may reveal a specific diagnosis that requires distinct treatment, and it would probably have an impact in lowering the mortality of these patients.

Ativação plaquetária em formas clínicas distintas da doença arterial coronariana (papel da P-selectina e de outros marcadores nas anginas estável e instável)

OBJETIVO: Os marcadores da ativacao plaquetaria em geral se apresentam elevados na doenca arterial coronariana. Desse modo, procuramos identificar a presenca e as potenciais associacoes de diferentes marcadores da ativacao plaquetaria. METODOS: Estudamos pacientes com angina instavel (n=28), pacientes com angina estavel (n=36) e pacientes sem doenca arterial coronariana (n=30); sexo e idade foram estratificados. Os niveis sanguineos da molecula de adesao P-selectina, do thromboxane B2 e de serotonina foram medidos por imunoensaios enzimaticos. RESULTADOS: Quando comparamos os grupos, os resultados foram: a P-selectina, o thromboxane B2 e os niveis do serotonina apresentaram-se significativamente mais elevados nos pacientes com angina instavel do que nos pacientes com angina estavel. CONCLUSAO: Estes marcadores da ativacao plaquetaria podem, portanto, identificar formas instaveis de doenca arterial coronariana.