Protocolo clínico de atendimento de pneumonia adquirida na comunidade para Pronto-Socorro Infantil do Hospital do Servidor Público Municipal de São Paulo / Clinical protocol for community-acquired pneumonia care for the Children's Emergency Room of the Hospital do Servidor Público Municipal de São Paulo

A pneumonia adquirida na comunidade (PAC) é a infecção aguda do parênquima pulmonar que ocorre no meio comunitário. A PAC representa a maior causa de morbidade e mortalidade em todo o mundo em crianças abaixo de cinco anos. Nesta faixa etária, a etiologia viral é a mais comum; porém, dentre as causas bacterianas, o Streptoccocus pneumoniae é o mais prevalente. As manifestações clínicas variam de acordo com o patógeno, hospedeiro e da gravidade da doença, sendo geralmente descrita com tosse, febre e desconforto respiratório. A PAC complicada é a pneumonia que, apesar do uso de antibióticos, evolui com complicações locais ou sistêmicas. Nos pacientes hospitalizados, as hemoculturas devem ser consideradas para auxiliar no diagnóstico etiológico e planejamento terapêutico. O tratamento inicial deve ser iniciado empiricamente com antibióticos. Caso haja necessidade de hospitalização, hemoculturas devem ser consideradas para auxiliar na propedêutica. Após implementação das vacinas pneumocócicas, principalmente após introdução da vacina pneumocócica 13 valente (PCV 13), houve redução significativa dos casos de pneumonia bacteriana e também da necessidade hospitalização. Diante de tal realidade, a elaboração do trabalho possui como objetivo a melhora dos procedimentos e a padronização dos atendimentos da população pediátrica com um quadro clínico sugestivo pneumonia adquirida na comunidade, que procura o serviço de Pronto Atendimento Infantil do Hospital do Servidor Público Municipal de São Paulo (HSPM), ao construir um protocolo clínico de atendimento específico para a doença. O presente trabalho objetiva elaborar um protocolo clínico de atendimento de pneumonia adquirida na comunidade no Hospital do Servidor Público Municipal de São Paulo, contribuindo na assistência médica dos pacientes pediátricos. Apesar do grande avanço com a introdução das vacinas pneumocócicas, a PAC ainda representa uma importante causa de mortalidade na população infantil, sendo fundamental a elaboração de protocolos clínicos para abordar corretamente os pacientes que recorrem a um Pronto Socorro Infantil. Protocolos clínicos são diretrizes fundamentadas nas melhores práticas para a abordagem e tratamento de determinadas doenças, baseadas em evidência científica. O presente trabalho objetiva a melhora dos procedimentos e a uniformização dos atendimentos da população pediátrica com pneumonia, que procura o serviço de Pronto Atendimento Infantil do Hospital do Servidor Público Municipal de São Paulo (HSPM), com a construção de um protocolo clínico de atendimento específico para a doença, a partir da revisão de literatura atualizada, cujo período de vigência seguirá os progressos científicos sobre o tema. Palavras-chave: Pneumonia Adquirida da Comunidade. Protocolos clínicos. Pediatria. Serviços Médicos de Emergência. Vacinas Pneumocócicas

Mind the gap: IgG4-related disease mimicking infectious cerebral mass lesions.

BACKGROUND: Cerebral intraparenchymal masses represent usually a neoplastic, or infectious differential diagnostic workup in neurology or infectious disease units. CASE PRESENTATION: Our patient was an 82-year-old male presenting with seizures, cerebral masses and a history of past treated pulmonary tuberculosis. Initial workup included a differential diagnosis of an infectious mass/multiple abscess. After exclusion of infectious or primary neoplastic origins by negative HIV serology, the absence of immune suppression, endocarditic lesions, negative results of blood cultures and bronchoalveolar lavage, negative cerebrospinal fluid workout on spinal tap led to exclusion of infectious causes. A surgical procedure was performed to access one of the lesions. This yielded a firm, cyst-like mass of histiocytic granulomatous tissue with a conspicuous plasmacellular component and a relevant IgG4 plasmacellular component consistent with IgG4-related disease. Steroid treatment determined conspicuous improvement and led to discharge of the patient. CONCLUSION: Parenchymal IgG4-related disease may be included as a new entity in the differential diagnosis of single or multiple cerebral masses in addition to infectious or neoplastic etiology.

A proposed prognostic prediction score for pleuroparenchymal fibroelastosis.

BACKGROUND: Clinical course of pleuroparenchymal fibroelastosis (PPFE) shows considerable variation among patients, but there is no established prognostic prediction model for PPFE. METHODS: The prediction model was developed using retrospective data from two cohorts: our single-center cohort and a nationwide multicenter cohort involving 21 institutions. Cox regression analyses were used to identify prognostic factors. The total score was defined as the weighted sum of values for the selected variables. The performance of the prediction models was evaluated by Harrell's concordance index (C-index). We also examined the usefulness of the gender-age-physiology (GAP) model for predicting the prognosis of PPFE patients. RESULTS: We examined 104 patients with PPFE (52 cases from each cohort). In a multivariate Cox analysis, a lower forced vital capacity (FVC [defined as FVC < 65%]; hazard ratio [HR], 2.23), a history of pneumothorax (HR, 3.27), the presence of a lower lobe interstitial lung disease (ILD) (HR, 2.31), and higher serum Krebs von den Lungen-6 (KL-6) levels (> 550 U/mL, HR, 2.56) were significantly associated with a poor prognosis. The total score was calculated as 1 × (FVC, < 65%) + 1 × (history of pneumothorax) + 1 × (presence of lower lobe ILD) + 1 × (KL-6, > 550 U/mL). PPFE patients were divided into three groups based on the prognostic score: stage I (0-1 points), stage II (2 points), and stage III (3-4 points). The survival rates were significantly different in each stage. The GAP stage was significantly associated with the prognosis of PPFE, but no difference was found between moderate (stage II) and severe (stage III) disease. Our new model for PPFE patients (PPFE Prognosis Score) showed better performance in the prediction of mortality in comparison to the GAP model (C-index of 0.713 vs. 0.649). CONCLUSIONS: Our new model for PPFE patients could be useful for predicting their prognosis.

Widespread brain parenchymal HMGB1 and NF-κB neuroinflammatory responses upon cortical spreading depolarization in familial hemiplegic migraine type 1 mice.

Neuroinflammatory changes involving neuronal HMGB1 release and astrocytic NF-κB nuclear translocation occur following cortical spreading depolarization (CSD) in wildtype (WT) mice but it is unknown to what extent this occurs in the migraine brain. We therefore investigated in familial hemiplegic migraine type 1 (FHM1) knock-in mice, which express an intrinsic hyperexcitability phenotype, the extent of neuroinflammation without and after CSD. CSD was evoked in one hemisphere by pinprick (single CSD) or topical KCl application (multiple CSDs). Neuroinflammatory (HMGB1, NF-κB) and neuronal activation (pERK) markers were investigated by immunohistochemistry in the brains of WT and FHM1 mutant mice without and after CSD. Effects of NMDA receptor antagonism on basal and CSD-induced neuroinflammatory changes were examined by, respectively, systemically administered MK801 and ifenprodil or topical MK801 application. In FHM1 mutant mice, CSD caused enhanced neuronal HMGB1 release and astrocytic NF-κB nuclear translocation in the cortex and subcortical areas that were equally high in both hemispheres. In WT mice such effects were only pronounced in the hemisphere in which CSD was induced. Neuroinflammatory responses were associated with pERK expression indicating neuronal activation. Upon CSD, contralateral cortical and striatal HMGB1 release was reduced by topical application of MK801 in the hemisphere contralateral to the one in which CSD was induced. This study reveals that neuroinflammatory activation after CSD is widespread and extends to the contralateral hemisphere, particularly in brains of FHM1 mutant mice. Effective blockade of CSD-induced neuroinflammatory responses in the contralateral hemisphere in FHM1 mice by local NMDA receptor antagonism suggests that neuronal hyperexcitability-related neuroinflammation is relevant in migraine pathophysiology, but possibly also other neurological disorders in which spreading depolarization is involved.

Acute Exacerbation of Pleuroparenchymal Fibroelastosis Secondary to Allogenic Hematopoietic Stem Cell Transplantation.

In this article, we report a case with pleuroparenchymal fibroelastosis (PPFE) following hematopoietic stem cell transplantation (HSCT) that developed acute respiratory failure with new bilateral ground glass opacity, which could not be explained by either a pulmonary infection, drug toxicity or extraparenchymal causes. Although combination therapy with multiple immunosuppressants was transiently effective, the patient died from a recurrent exacerbation. Autopsied lungs demonstrated diffuse alveolar damage superimposed on PPFE. There was no evidence of any coexisting interstitial pneumonia with the usual interstitial pneumonia (UIP) pattern. Our case suggests that acute exacerbation can occur in patients with post-HSCT PPFE, even when a coexisting UIP pattern is absent.

Pulmonary complications associated with veno-arterial extra-corporeal membrane oxygenation: a comprehensive review.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving technology that provides transient respiratory and circulatory support for patients with profound cardiogenic shock or refractory cardiac arrest. Among its potential complications, VA-ECMO may adversely affect lung function through various pathophysiological mechanisms. The interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response which may increase pulmonary vascular permeability and promote the sequestration of polymorphonuclear neutrophils within the lung parenchyma. Also, VA-ECMO increases the afterload of the left ventricle (LV) through reverse flow within the thoracic aorta, resulting in increased LV filling pressure and pulmonary congestion. Furthermore, VA-ECMO may result in long-standing pulmonary hypoxia, due to partial shunting of the pulmonary circulation and to reduced pulsatile blood flow within the bronchial circulation. Ultimately, these different abnormalities may result in a state of persisting lung inflammation and fibrotic changes with concomitant functional impairment, which may compromise weaning from VA-ECMO and could possibly result in long-term lung dysfunction. This review presents the mechanisms of lung damage and dysfunction under VA-ECMO and discusses potential strategies to prevent and treat such alterations.

Small damage of brain parenchyma reliably triggers spreading depolarization.

Objectives: Spreading depolarization (SD) is a well-recognized component of the stress response of the cortex to its acute injury. Cortical SD has been shown to occur in severe brain insults and standard neurosurgical procedures in patients and is supposed to promote delayed secondary brain injuries. Stereotactic surgery and site-specific intracerebral microinjections produce a small tissue injury when a thin needle is inserted directly into the brain parenchyma (via the cannula guide). The present study was designed to examine whether such a parenchymal damage can trigger SD.Methods: Experiments were performed in awake freely moving rats with simultaneous video-monitoring of behavior and recording of SD-related DC potentials in the cortex and striatum. A parenchymal damage was produced by 1-mm protruding of thin (0.3-mm diameter) cannula beyond the tip of cannula guide preliminary implanted into the amygdala or deep cortical layers.Results: We found that the micro-injury of the brain parenchyma the volume of which did not exceed 0.3 mm3 was sufficient to initiate SD in a very high proportion of rats (75-100%). The amygdala showed increased resistance against the injury-induced SD compared to the cortex. We further showed that SD triggered by the local micro-injury invaded remote intact regions of the cortico-striatal system and evoked specific changes in spontaneous animal behavior.Discussion: The findings indicate that SD may represent a previously unidentified side effect of local parenchymal injury during site-specific microinjections and stereotactic surgery.

Could semiquantitative analysis of real-time ultrasound elastography distinguish more liver parenchyma alterations of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome?

ABSTRACT Objective: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. Subjects and methods: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. Results: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. Conclusion: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

Could semiquantitative analysis of real-time ultrasound elastography distinguish more liver parenchyma alterations of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome?

OBJECTIVE: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. SUBJECTS AND METHODS: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. RESULTS: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. CONCLUSION: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

Ultrasonographic evaluation of lung parenchyma involvement in sarcoidosis.

PURPOSE: To use ultrasonography (USG) for the evaluation of lung parenchyma in patients with sarcoidosis, andto compare the USG findings with the results of a high-resolution computerized tomography (HRCT) and pulmonary function test-carbon monoxide diffusion test (PFT-DLCO), which are commonly used methods in the evaluation of parenchymal involvement in sarcoidosis. MATERIAL AND METHODS: Patients with sarcoidosis and healthy controls were enrolled in the study between January 2015 and December 2017. The clinical findings, HRCT and PFT-DLCO results of all subjects were recorded, and USG findings and comet tail artifact (CTA) measurements were recorded by another pulmonologist. The USG, HRCT and SFT-DLCO findings were compared between the two groups. Based on the findings of theclinical-radiologic investigations and PFT-DLCO, as the current gold standard in diagnosis, the sensitivity and specificity of USG in demonstrating lung parenchyma involvement in sarcoidosis patients were estimated. FINDINGS: The sarcoidosis group consisted of 79 patients and the control group included 34 subjects. The mean number of CTAs in the sarcoidosis and control groups was 33.4 and 25, respectively (p=0.001). In the sarcoidosis group, the number of CTAs in patients with DLCO% <80 and ≥80% was 37.4 and 29.7, respectively (p=0.011), and a negative correlation was identified between the number of CTAs and DLCO% (p=0.019 r=-0.267). The mean number of CTAs in patients with and without parenchymal involvement in HRCT was 36 and 25.5, respectively (p=0.001). The number of CTAs in the patients with sarcoidosis with a normal DLCO% value (≥80%) was higher than in the control group (p=0.014). The diagnostic sensitivity and specificity of thoracic USG were found to be 76% and 53%, respectively. CONCLUSION: The number of CTAs in patients with sarcoidosis was higher than that of the healthy controls. The number of CTAs in patients with sarcoidosis with parenchymal involvement in HRCT and/or a low DLCO (<80%) was also elevated. Thoracic USG has a high sensitivity (76%) in demonstrating parenchymal involvement in patients with sarcoidosis.

Reduced spinal cord parenchymal cerebrospinal fluid circulation in experimental autoimmune encephalomyelitis.

An alteration of parenchymal cerebrospinal fluid circulation (CSF) has been proposed to take part in the pathophysiology of multiple sclerosis. By using an intragate T1-weighted high-resolution MRI of the spinal cord of freely breathing mice injected with a gadolinium chelate in the cisterna magna, we show that a parenchymal CSF circulation exists in the spinal cord, in addition to that originally described in the brain. In experimental autoimmune encephalomyelitis, a model of multiple sclerosis, we show a reduction of parenchymal CSF circulation specifically in the spinal cord but not in the brain.

ARFI shear-wave elastography with simulation of acute urinary tract obstruction in an ex vivo porcine kidney model.

METHODS: A total of 20 heparinized pig kidneys were investigated at 10 intrapelvic hydrostatic pressure steps (0-90 mmHg). SWE (ARFI; Virtual TouchTM IQ, Siemens) measurements were taken at three different measuring regions and in two measuring sequences using a linear ultrasonography probe (9L4, Siemens). Median values of 10 shear-wave speed (SWS) measurements were calculated for each pressure step. Logarithmic transformed median SWS values were analyzed in a linear mixed model. RESULTS: SWS increased significantly with increasing intrapelvic pressure. Median SWS for all kidneys in both measuring sequences and all measuring regions was 1.47 m/s (interquartile range [IQR], 0.38 m/s) at 0 mmHg, 1.94 m/s (IQR, 0.42 m/s) at 30 mmHg, 2.07 m/s (IQR, 0.43 m/s) at 60 mmHg, 2.24 m/s (IQR, 0.49 m/s) at 90 mmHg. The correlation between pelvic pressure increase and median SWS values for the central parenchyma was significantly higher compared with the peripheral parenchyma. CONCLUSION: Acutely increased renal pelvic pressure correlates with increasing SWS values in ARFI elastography in an ex vivo porcine kidney model.

Magnetic resonance imaging provides evidence of glymphatic drainage from human brain to cervical lymph nodes.

Pre-clinical research in rodents provides evidence that the central nervous system (CNS) has functional lymphatic vessels. In-vivo observations in humans, however, are not demonstrated. We here show data on CNS lymphatic drainage to cervical lymph nodes in-vivo by magnetic resonance imaging (MRI) enhanced with an intrathecal contrast agent as a cerebrospinal fluid (CSF) tracer. Standardized MRI of the intracranial compartment and the neck were acquired before and up to 24-48 hours following intrathecal contrast agent administration in 19 individuals. Contrast enhancement was radiologically confirmed by signal changes in CSF nearby inferior frontal gyrus, brain parenchyma of inferior frontal gyrus, parahippocampal gyrus, thalamus and pons, and parenchyma of cervical lymph node, and with sagittal sinus and neck muscle serving as reference tissue for cranial and neck MRI acquisitions, respectively. Time series of changes in signal intensity shows that contrast enhancement within CSF precedes glymphatic enhancement and peaks at 4-6 hours following intrathecal injection. Cervical lymph node enhancement coincides in time with peak glymphatic enhancement, with peak after 24 hours. Our findings provide in-vivo evidence of CSF tracer drainage to cervical lymph nodes in humans. The time course of lymph node enhancement coincided with brain glymphatic enhancement rather than with CSF enhancement.

Understanding Pulmonary Stress-Strain Relationships in Severe ARDS and Its Implications for Designing a Safer Approach to Setting the Ventilator.

This review describes the current understanding of the lungs' response to deforming stress under conditions of both normal physiology and acute lung injury. Several limiting assumptions are needed to infer lung parenchymal stress and strain from airway pressure, volume, and flow data from mechanically ventilated patients with injured lungs. These assumptions include the effects of the chest wall on lung-surface pressure, its topographical distribution, and the effects of non-uniform tissue properties on local parenchymal stresses. In addition, there is a spectrum of biophysical lung injury mechanisms that involves normal as well as tangential alveolar wall stresses. To these are added important secondary effects on pulmonary vascular resistance and right heart function. Understanding both the assumptions of lung mechanics and the scope of injury mechanisms operating during ARDS is necessary to interpret the results of clinical trials that inform prevailing ventilator-management guidelines. The implications issuing from these 3 topics inform a safer approach to setting and adjusting the ventilator to minimize the risk of ventilator-induced lung injury. This is enumerated in a 5-step approach that can be used to guide ventilator management of unstable patients with severe lung injury.

Parenchymal Pressure Inconsistency in Different Brain Areas After Kaolin Injection into the Subarachnoid Space of Neonatal Rats.

AIM: To describe the relationship between the parenchymal pressure changes and the development of hydrocephalus in kaolininjected neonatal rats according to cerebral regions and time intervals of developing hydrocephalus. MATERIAL AND METHODS: Neonatal rats aged 2 to 3 days were examined in 5 groups as kaolin frontal "K-F", kaolin parietal "KP", saline frontal "SF-F", saline parietal "SF-P" and control "C", based on the injected material and injection sites. All injections were performed into the cortical subarachnoid space of the right frontal and right parietal regions. The fifth group was injection free. On the 3 < sup > rd < /sup > , 7 < sup > th < /sup > , 15 < sup > th < /sup > , 30 < sup > th < /sup > and 60 < sup > th < /sup > days after injection, parenchymal pressures (PP) of 5-7 rats from each group were measured from different regions. RESULTS: We compared the control group with saline-injected and kaolin-injected groups and found statistically significant parenchymal pressure differences based on regional measurements. In the kaolin groups, the mean PP values were obviously higher than the saline-injected group. Within each kaolin-injected group, the pressure values were variable and inconsistent regarding the parenchymal regions. CONCLUSION: Hydrocephalus cannot be totally explained with existent "bulk-flow" or "hydrodynamic" theories. Although our experimental design was planned to develop hydrocephalus according to the bulk flow theory, our results were more compatible with the hydrodynamic theory. The present comments on the occurrence and pathogenesis of hydrocephalus are still open to debate and may require further comprehensive studies.

The assessment of renal cortex and parenchymal volume using automated CT volumetry for predicting renal function after donor nephrectomy.

BACKGROUND: Contrast-enhanced CT is necessary before donor nephrectomy and is usually combined with a Tc-99m-mercapto-acetyltriglycine (MAG3) scan to check split renal function (SRF). However, all transplant programs do not use MAG3 because of its high cost and exposure to radiation. We examined whether CT volumetry of the kidney can be a new tool for evaluating SRF. METHODS: Sixty-three patients underwent live donor nephrectomy. Patients without a 1.0 mm slice CT or follow-up for <12 months were excluded leaving 34 patients' data being analyzed. SRF was measured by MAG3. Split renal volume (SRV) was calculated automatically using volume analyzer software. The correlation between SRF and SRV was examined. The association between the donor's postoperative estimated glomerular filtration rate (eGFR) and predicted eGFR calculated by MAG3 or CT volumetry was analyzed at 1, 3, and 12 months post nephrectomy. RESULTS: Strong correlations were observed preoperatively in a Bland-Altman plot between SRF measured by MAG3 and either CT cortex or parenchymal volumetry. In addition, eGFR after donation correlated with SRF measured by MAG3 or CT volumetry. The correlation coefficients (R) for eGFR Mag3 split were 0.755, 0.615, and 0.763 at 1, 3 and 12 months, respectively. The corresponding R values for cortex volume split were 0.679, 0.638, and 0.747. Those for parenchymal volume split were 0.806, 0.592, and 0.764. CONCLUSION: Measuring kidney by CT volumetry is a cost-effective alternative to MAG3 for evaluating SRF and predicting postoperative donor renal function. Both cortex and parenchymal volumetry were similarly effective.

The Pathology of Chronic Obstructive Pulmonary Disease: Progress in the 20th and 21st Centuries.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and is the fourth leading cause of death worldwide. There has been significant progress in the pathologic description and pathophysiologic analysis of COPD in the 20th and 21st centuries. We review the history, progression, and significance of pathologic alterations in COPD, including emphysematous changes, airway alterations, and vascular alterations. We also indicate what pathologic features of COPD the practicing pathologist should be describing in standard surgical and autopsy specimens.

Pathogenesis of Nonalcoholic Steatohepatitis: Interactions between Liver Parenchymal and Nonparenchymal Cells.

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in the Western countries, affecting up to 25% of the general population and becoming a major health concern in both adults and children. NAFLD encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is a manifestation of the metabolic syndrome and hepatic disorders with the presence of steatosis, hepatocyte injury (ballooning), inflammation, and, in some patients, progressive fibrosis leading to cirrhosis. The pathogenesis of NASH is a complex process and implicates cell interactions between liver parenchymal and nonparenchymal cells as well as crosstalk between various immune cell populations in liver. Lipotoxicity appears to be the central driver of hepatic cellular injury via oxidative stress and endoplasmic reticulum (ER) stress. This review focuses on the contributions of hepatocytes and nonparenchymal cells to NASH, assessing their potential applications to the development of novel therapeutic agents. Currently, there are limited pharmacological treatments for NASH; therefore, an increased understanding of NASH pathogenesis is pertinent to improve disease interventions in the future.

[HYPOTHERMIA INFLUENCES ON OXYGEN TENSION IN THE BRAIN PARENCHYMA IN PATIENTS WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE].

Aneurysmal subarachnoid hemorrhage is a serious medical and social problem. The main physiological mechanisms that determine secondary brain damage in this patients are intracranial hypertension, cerebral vasospasm, dysfunction of autoregulation mechanisms, violation of liquorodynamics and delayed cerebral ischemia. The multimodal neuromonitoring for prevention and timely correction ofsecondary brain injury factors has become routine practice in neuroICU. Measurement of oxygen tension in the brain parenchyma is one of neuromonitoring options. During the years of intensive use of this method in clinical practice the reasons for reducing the oxygen tension in the brain parenchyma were revealed, as well as developed and clinically validated algorithms for correction of such conditions. However, there are clinical situations that are difficult to interpret and even more difficult to make the right tactical and therapeutic solutions. We present the clinical observation of the patient with aneurysmal subarachnoid hemorrhage, who had dramatically reduced brain intraparenchymal oxygen pressure although prolonged hypothermia were used. Despite this, the outcome was favorable. The analysis allowed to assume that the reason for this decrease in oxygen tension in the brain parenchyma could be hypothermia itself