Management of intracranial hypertension(IH)has improved in the last decades driven by advancements in monitoring technologies and a deeper understanding of its pathophysiology.Although intracranial pressure(ICP)cathet...Management of intracranial hypertension(IH)has improved in the last decades driven by advancements in monitoring technologies and a deeper understanding of its pathophysiology.Although intracranial pressure(ICP)catheters are still recommended by current guidelines for monitoring patients at risk of IH,these methods are not without limitations.Challenges include procedural complications,availability of these devices in many healthcare settings and technical issues.In this context,management in the absence of ICP monitoring is common and now it can be augmented by intensivist-led point-of-care ultrasound,which includes tools such as transcranial doppler,optic nerve sheath measurement and brain ultrasound.These methods offer anatomic information that can sometimes withhold repeated head computed tomography(CT)scans,but they are also a window into ICP dynamics without the associated risks of invasive monitoring and are reasonable alternatives for guiding treatment,provided an integration between neurological examination,head CT anatomical findings and noninvasive monitors is considered.This manuscript synthesizes the evidence for using invasive ICP monitoring and methods for non-invasive monitoring,more focused on the role of ultrasound,given its wider availability.We also propose a practical approach of how to integrate this information at bedside to avoid both under and overtreatment,by embracing a clinical epidemiology paradigm to guide management decisions.展开更多
The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. ...The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of nonimmune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct proinflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in IBD.The effects determine pathologic changes,which may sustain chronic intestinal inflammation and also underlie specific disease phenotypes.In addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers,research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.展开更多
BACKGROUND 1,3-beta-D-glucan(BG)is a ubiquitous cell wall component of gut microorganisms.We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel di...BACKGROUND 1,3-beta-D-glucan(BG)is a ubiquitous cell wall component of gut microorganisms.We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel disease.AIM To determine whether the serum BG concentrations correlate with intestinal inflammation.METHODS A prospective observational study was performed in a tertiary referral center,from 2016 to 2019,in which serum BG was determined in 115 patients with Crohn’s disease(CD),51 with ulcerative colitis(UC),and 82 controls using a photometric detection kit.Inflammatory activity was determined by ileocolonoscopy,histopathology,magnetic resonance enterography,and biomarkers,including fecal calprotectin(FC),C-reactive protein,and a panel of cytokines.The ability of BG to detect active vs inactive disease was assessed using the area under the receiver operating characteristic curve.In subgroup analysis,serial BG was used to assess the response to therapeutic interventions.RESULTS The serum BG levels were higher in CD patients than in controls(P=0.0001).The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients.The area under the curve(AUC)in receiver operating characteristic analysis to predict endoscopic activity was 0.694[95%confidence interval(CI):0.60-0.79;P=0.001]in CD,and 0.662(95%CI:0.51-0.81;P=0.066)in UC patients.The AUC in receiver operating characteristic analysis to predict histologic activity was 0.860(95%CI:0.77-0.95;P<0.001)in CD,and 0.786(95%CI:0.57-0.99;P=0.015)in UC patients.The cut-off values of BG for both endoscopic and histologic activity were 60μg/mL in CD,and 40μg/mL in UC patients.Performance analysis showed that the results based on BG of 40 and 60μg/mL were more specific for predicting endoscopic activity(71.8%and 87.2%for CD;and 87.5%and 87.5%for UC,respectively)than FC(53.3%and 66.7%for CD;and 20%and 80%for UC,respectively);and also histologic activity(60.5%and 76.3%for CD;and 90.0%and 95.0%for UC,respectively)than FC(41.7%and 50.0%for CD;and 25%and 50%for UC,respectively).Regarding the clinical,endoscopic,and histologic activities,the BG levels were reduced following therapeutic intervention in patients with CD(P<0.0001)and UC(P=0.003).Compared with endoscopic(AUC:0.693;P=0.002)and histologic(AUC:0.868;P<0.001)activity,no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography(AUC:0.576;P=0.192).Positive correlations were detected between BG and IL-17 in the CD(r:0.737;P=0.001)and the UC group(r:0.574;P=0.005),and between BG and interferon-gamma in the CD group(r:0.597;P=0.015).CONCLUSION Serum BG may represent an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring inflammatory bowel diseases,particularly in CD.展开更多
BACKGROUND Acid-base imbalance has been poorly described in patients with coronavirus disease 2019(COVID-19).Study by the quantitative acid-base approach may be able to account for minor changes in ion distribution th...BACKGROUND Acid-base imbalance has been poorly described in patients with coronavirus disease 2019(COVID-19).Study by the quantitative acid-base approach may be able to account for minor changes in ion distribution that may have been over-looked using traditional acid-base analysis techniques.In a cohort of critically ill COVID-19 patients,we looked for an association between metabolic acidosis surrogates and worse clinical outcomes,such as mortality,renal dialysis,and length of hospital stay.AIM To describe the acid-base disorders of critically ill COVID-19 patients using Stewart’s approach,associating its variables with poor outcomes.METHODS This study pertained to a retrospective cohort comprised of adult patients who experienced an intensive care unit stay exceeding 4 days and who were diagnosed with severe acute respiratory syndrome coronavirus 2 infection through a positive polymerase chain reaction analysis of a nasal swab and typical pulmonary involvement observed in chest computed tomography scan.Laboratory and clinical data were obtained from electronic records.Categorical variables were compared using Fisher’s exact test.Continuous data were presented as median and interquartile range.The Mann-Whitney U test was used for comparisons.RESULTS In total,211 patients were analyzed.The mortality rate was 13.7%.Overall,149 patients(70.6%)presented with alkalosis,28 patients(13.3%)had acidosis,and the remaining 34 patients(16.2%)had a normal arterial pondus hydrogenii.Of those presenting with acidosis,most had a low apparent strong ion difference(SID)(20 patients,9.5%).Within the group with alkalosis,128 patients(61.0%)had respiratory origin.The non-survivors were older,had more comorbidities,and had higher Charlson’s and simplified acute physiology score 3.We did not find severe acid-base imbalance in this population.The analyzed Stewart’s variables(effective SID,apparent SID,and strong ion gap and the effect of albumin,lactate,phosphorus,and chloride)were not different between the groups.CONCLUSION Alkalemia is prevalent in COVID-19 patients.Although we did not find an association between acid-base variables and mortality,the use of Stewart’s methodology may provide insights into this severe disease.展开更多
Although efforts have been made to improve the pharmacological treatment of depression,approximately one-third of patients with depression do not respond to conventional therapy using antidepressants.Other potential n...Although efforts have been made to improve the pharmacological treatment of depression,approximately one-third of patients with depression do not respond to conventional therapy using antidepressants.Other potential non-pharmacological therapies have been studied in the last years,including the use of mesenchymal stem cell therapies to treat depression.These therapies are reviewed here since it is clinically relevant to develop innovative therapeutics to treat psychiatric patients.Experimental data corroborate that mesenchymal stem cell therapy could be considered a potential treatment for depression based on its antiinflammatory and neurotrophic properties.However,some clinical trials involving treatment of depression with stem cells are in progress,but with no published results.These studies and other future clinical investigations will be crucial to define how much mesenchymal stem cells can effectively be used in psychiatric clinics as a strategy for supporting depression treatment.展开更多
Patients with cirrhosis have an increased risk of infection and differently from other complications,that over the years are improving in their outcomes,infections in cirrhotic patients are still a major cause of hosp...Patients with cirrhosis have an increased risk of infection and differently from other complications,that over the years are improving in their outcomes,infections in cirrhotic patients are still a major cause of hospitalization and death(up to 50%in-hospital mortality).Infections by multidrug-resistant organisms(MDRO)have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact.About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years.MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution.An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects,such as the type of infection(spontaneous bacterial peritonitis,pneumonia,urinary tract infection and spontaneous bacteremia),bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition(community acquired,healthcare associated or nosocomial).Furthermore,regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology.Antibiotic treatment is the most effective measure to treat infections caused by MDRO.Therefore,optimizing antibiotic prescribing is critical to effectively treat these infections.Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality.On the other hand,the supply of new agents to treat these infections is very limited.Thus,specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.展开更多
文摘Management of intracranial hypertension(IH)has improved in the last decades driven by advancements in monitoring technologies and a deeper understanding of its pathophysiology.Although intracranial pressure(ICP)catheters are still recommended by current guidelines for monitoring patients at risk of IH,these methods are not without limitations.Challenges include procedural complications,availability of these devices in many healthcare settings and technical issues.In this context,management in the absence of ICP monitoring is common and now it can be augmented by intensivist-led point-of-care ultrasound,which includes tools such as transcranial doppler,optic nerve sheath measurement and brain ultrasound.These methods offer anatomic information that can sometimes withhold repeated head computed tomography(CT)scans,but they are also a window into ICP dynamics without the associated risks of invasive monitoring and are reasonable alternatives for guiding treatment,provided an integration between neurological examination,head CT anatomical findings and noninvasive monitors is considered.This manuscript synthesizes the evidence for using invasive ICP monitoring and methods for non-invasive monitoring,more focused on the role of ultrasound,given its wider availability.We also propose a practical approach of how to integrate this information at bedside to avoid both under and overtreatment,by embracing a clinical epidemiology paradigm to guide management decisions.
基金Supported by the Brazilian research foundations Fundacao de Amparo à Pesquisa do Estado do Rio de Janeiro--FAPERJ,No.E26/202.781/2017Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq,No.302401/2016-4
文摘The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of nonimmune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct proinflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in IBD.The effects determine pathologic changes,which may sustain chronic intestinal inflammation and also underlie specific disease phenotypes.In addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers,research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.
文摘BACKGROUND 1,3-beta-D-glucan(BG)is a ubiquitous cell wall component of gut microorganisms.We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel disease.AIM To determine whether the serum BG concentrations correlate with intestinal inflammation.METHODS A prospective observational study was performed in a tertiary referral center,from 2016 to 2019,in which serum BG was determined in 115 patients with Crohn’s disease(CD),51 with ulcerative colitis(UC),and 82 controls using a photometric detection kit.Inflammatory activity was determined by ileocolonoscopy,histopathology,magnetic resonance enterography,and biomarkers,including fecal calprotectin(FC),C-reactive protein,and a panel of cytokines.The ability of BG to detect active vs inactive disease was assessed using the area under the receiver operating characteristic curve.In subgroup analysis,serial BG was used to assess the response to therapeutic interventions.RESULTS The serum BG levels were higher in CD patients than in controls(P=0.0001).The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients.The area under the curve(AUC)in receiver operating characteristic analysis to predict endoscopic activity was 0.694[95%confidence interval(CI):0.60-0.79;P=0.001]in CD,and 0.662(95%CI:0.51-0.81;P=0.066)in UC patients.The AUC in receiver operating characteristic analysis to predict histologic activity was 0.860(95%CI:0.77-0.95;P<0.001)in CD,and 0.786(95%CI:0.57-0.99;P=0.015)in UC patients.The cut-off values of BG for both endoscopic and histologic activity were 60μg/mL in CD,and 40μg/mL in UC patients.Performance analysis showed that the results based on BG of 40 and 60μg/mL were more specific for predicting endoscopic activity(71.8%and 87.2%for CD;and 87.5%and 87.5%for UC,respectively)than FC(53.3%and 66.7%for CD;and 20%and 80%for UC,respectively);and also histologic activity(60.5%and 76.3%for CD;and 90.0%and 95.0%for UC,respectively)than FC(41.7%and 50.0%for CD;and 25%and 50%for UC,respectively).Regarding the clinical,endoscopic,and histologic activities,the BG levels were reduced following therapeutic intervention in patients with CD(P<0.0001)and UC(P=0.003).Compared with endoscopic(AUC:0.693;P=0.002)and histologic(AUC:0.868;P<0.001)activity,no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography(AUC:0.576;P=0.192).Positive correlations were detected between BG and IL-17 in the CD(r:0.737;P=0.001)and the UC group(r:0.574;P=0.005),and between BG and interferon-gamma in the CD group(r:0.597;P=0.015).CONCLUSION Serum BG may represent an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring inflammatory bowel diseases,particularly in CD.
文摘BACKGROUND Acid-base imbalance has been poorly described in patients with coronavirus disease 2019(COVID-19).Study by the quantitative acid-base approach may be able to account for minor changes in ion distribution that may have been over-looked using traditional acid-base analysis techniques.In a cohort of critically ill COVID-19 patients,we looked for an association between metabolic acidosis surrogates and worse clinical outcomes,such as mortality,renal dialysis,and length of hospital stay.AIM To describe the acid-base disorders of critically ill COVID-19 patients using Stewart’s approach,associating its variables with poor outcomes.METHODS This study pertained to a retrospective cohort comprised of adult patients who experienced an intensive care unit stay exceeding 4 days and who were diagnosed with severe acute respiratory syndrome coronavirus 2 infection through a positive polymerase chain reaction analysis of a nasal swab and typical pulmonary involvement observed in chest computed tomography scan.Laboratory and clinical data were obtained from electronic records.Categorical variables were compared using Fisher’s exact test.Continuous data were presented as median and interquartile range.The Mann-Whitney U test was used for comparisons.RESULTS In total,211 patients were analyzed.The mortality rate was 13.7%.Overall,149 patients(70.6%)presented with alkalosis,28 patients(13.3%)had acidosis,and the remaining 34 patients(16.2%)had a normal arterial pondus hydrogenii.Of those presenting with acidosis,most had a low apparent strong ion difference(SID)(20 patients,9.5%).Within the group with alkalosis,128 patients(61.0%)had respiratory origin.The non-survivors were older,had more comorbidities,and had higher Charlson’s and simplified acute physiology score 3.We did not find severe acid-base imbalance in this population.The analyzed Stewart’s variables(effective SID,apparent SID,and strong ion gap and the effect of albumin,lactate,phosphorus,and chloride)were not different between the groups.CONCLUSION Alkalemia is prevalent in COVID-19 patients.Although we did not find an association between acid-base variables and mortality,the use of Stewart’s methodology may provide insights into this severe disease.
基金Supported by Conselho Nacional de Desenvolvimento Cientifico-CNPq.
文摘Although efforts have been made to improve the pharmacological treatment of depression,approximately one-third of patients with depression do not respond to conventional therapy using antidepressants.Other potential non-pharmacological therapies have been studied in the last years,including the use of mesenchymal stem cell therapies to treat depression.These therapies are reviewed here since it is clinically relevant to develop innovative therapeutics to treat psychiatric patients.Experimental data corroborate that mesenchymal stem cell therapy could be considered a potential treatment for depression based on its antiinflammatory and neurotrophic properties.However,some clinical trials involving treatment of depression with stem cells are in progress,but with no published results.These studies and other future clinical investigations will be crucial to define how much mesenchymal stem cells can effectively be used in psychiatric clinics as a strategy for supporting depression treatment.
文摘Patients with cirrhosis have an increased risk of infection and differently from other complications,that over the years are improving in their outcomes,infections in cirrhotic patients are still a major cause of hospitalization and death(up to 50%in-hospital mortality).Infections by multidrug-resistant organisms(MDRO)have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact.About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years.MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution.An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects,such as the type of infection(spontaneous bacterial peritonitis,pneumonia,urinary tract infection and spontaneous bacteremia),bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition(community acquired,healthcare associated or nosocomial).Furthermore,regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology.Antibiotic treatment is the most effective measure to treat infections caused by MDRO.Therefore,optimizing antibiotic prescribing is critical to effectively treat these infections.Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality.On the other hand,the supply of new agents to treat these infections is very limited.Thus,specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.
