Brain tight junction protein expression in sepsis in an autopsy series.

BACKGROUND: Neuroinflammation often develops in sepsis along with increasing permeability of the blood-brain barrier (BBB), which leads to septic encephalopathy. The barrier is formed by tight junction structures between the cerebral endothelial cells. We investigated the expression of tight junction proteins related to endothelial permeability in brain autopsy specimens in critically ill patients deceased with sepsis and analyzed the relationship of BBB damage with measures of systemic inflammation and systemic organ dysfunction. METHODS: The case series included all (385) adult patients deceased due to sepsis in the years 2007-2015 with available brain specimens taken at autopsy. Specimens were categorized according to anatomical location (cerebrum, cerebellum). The immunohistochemical stainings were performed for occludin, ZO-1, and claudin. Patients were categorized as having BBB damage if there was no expression of occludin in the endothelium of cerebral microvessels. RESULTS: Brain tissue samples were available in 47 autopsies, of which 38% (18/47) had no expression of occludin in the endothelium of cerebral microvessels, 34% (16/47) developed multiple organ failure before death, and 74.5% (35/47) had septic shock. The deceased with BBB damage had higher maximum SOFA scores (16 vs. 14, p = 0.04) and more often had procalcitonin levels above 10 µg/L (56% vs. 28%, p = 0.045) during their ICU stay. BBB damage in the cerebellum was more common in cases with C-reactive protein (CRP) above 100 mg/L as compared with CRP less than 100 (69% vs. 25%, p = 0.025). CONCLUSIONS: In fatal sepsis, damaged BBB defined as a loss of cerebral endothelial expression of occludin is related with severe organ dysfunction and systemic inflammation.

Elevated serum S-100ß in patients with septic shock is associated with delirium.

BACKGROUND: A high prevalence of delirium is observed in sepsis, yet specific markers for this brain dysfunction in sedated patients are still lacking. Cytoplasmic low molecular weight calcium-binding protein, S-100ß, is a commonly used nonspecific marker for brain injury. Here, we evaluated whether delirium is associated with increases in S-100ß levels. METHODS: This observational study included 22 patients with septic shock. Delirium was assessed by CAM-ICU and blood samples were obtained to measure inflammatory (CRP, PCT, IL-6, IL-17, TNF-α) and cerebral biomarkers (S-100ß, NSE, HAB42, SUBP). Patients were categorized according to the presence of delirium. RESULTS: Delirium was present in 10/22 of the patients (45.5%). Serum S-100ß levels were above the laboratory cutoff value of 0.15 µg/L in 13/22 (59.1%) of the patients. The odds ratio for risk of developing delirium in cases with an S-100ß >0.15 µg/L was 18.0 (95%CI, 1.7-196.3, P = 0.011). Patients with delirium had higher plasma levels of IL-6 compared to those without; 138.3 pg/mL [28.0-296.7] vs 53.6 pg/mL [109.3-505, P = 0.050]. There was a positive correlation between S100 ß and IL-6 levels (r = 0.489, P = 0.021). Delirium patients had higher SOFA scores; 10 [5-9] vs 7[8-10.5], P = 0.036. CONCLUSIONS: Delirium in septic shock was associated with an elevated protein S-100ß when using a laboratory cutoff value of 0.15 µg/L and with more severe organ dysfunction during the ICU stay.

Interleukin-5, interleukin-6, interferon induced protein-10, procalcitonin and C-reactive protein among mechanically ventilated severe community-acquired viral and bacterial pneumonia patients.

BACKGROUND: The serum cytokine levels among 45 mechanically ventilated, intensive care unit (ICU)-treated severe community-acquired pneumonia (SCAP) patients with known microbial etiology in three different etiology groups were assessed. METHODS: Blood samples for C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-5, IL-6, IL-10, human interferon gamma induced protein (IP)-10, and TNF-α (tumor necrosis factor alpha) were collected at time points 0, 12, 24, 48, 72 and 96 h after study inclusion. RESULTS: There were 21 (43%) pure bacterial infections (bacterial group, BG), 5 (10%) pure viral infections (viral group, VG), and 19 (39%) mixed bacterial-viral infections (mixed group, MG) among 45 mechanically ventilated SCAP patients. CRP and PCT levels were significantly higher in the MG and values decreased with time in all groups. PCT differed also in time and group analysis (P = 0.001), the highest being in the MG. IL-5 levels were significantly higher in the VG compared to others (Ptime = 0.001, Pgroup = 0.051 and Ptimexgroup = 0.016). IL-6 and IP-10 levels decreased over time (Ptime = 0.003 and Ptime = 0.021), but there were no differences between groups. CONCLUSION: SCAP patients with viral etiology have higher IL-5 levels. Patients with mixed viral and bacterial group have higher PCT compared to other etiologies.

Retinal arterial blood flow and retinal changes in patients with sepsis: preliminary study using fluorescein angiography.

BACKGROUND: Although tissue perfusion is often decreased in patients with sepsis, the relationship between macrohemodynamics and microcirculatory blood flow is poorly understood. We hypothesized that alterations in retinal blood flow visualized by angiography may be related to macrohemodynamics, inflammatory mediators, and retinal microcirculatory changes. METHODS: Retinal fluorescein angiography was performed twice during the first 5 days in the intensive care unit to observe retinal abnormalities in patients with sepsis. Retinal changes were documented by hyperfluorescence angiography; retinal blood flow was measured as retinal arterial filling time (RAFT); and intraocular pressure was determined. In the analyses, we used the RAFT measured from the eye with worse microvascular retinal changes. Blood samples for inflammation and cerebral biomarkers were collected, and macrohemodynamics were monitored. RAFT was categorized as prolonged if it was more than 8.3 seconds. RESULTS: Of 31 patients, 29 (93%) were in septic shock, 30 (97%) required mechanical ventilation, 22 (71%) developed delirium, and 16 (51.6%) had retinal angiopathies, 75% of which were bilateral. Patients with prolonged RAFT had a lower cardiac index before (2.1 L/kg/m2 vs. 3.1 L/kg/m2, P = 0.042) and during angiography (2.1 L/kg/m2 vs. 2.6 L/kg/m2, P = 0.039). They more frequently had retinal changes (81% vs. 20%, P = 0.001) and higher intraocular pressure (18 mmHg vs. 14 mmHg, P = 0.031). Patients with prolonged RAFT had lower C-reactive protein (139 mg/L vs. 254 mg/L, P = 0.011) and interleukin-6 (39 pg/ml vs. 101 pg/ml, P < 0.001) than those with shorter RAFT. CONCLUSIONS: Retinal angiopathic changes were more frequent and cardiac index was lower in patients with prolonged RAFT, whereas patients with shorter filling times had higher levels of inflammatory markers.

The impact of antemortem computed tomographic scanning on postmortem examination rate and frequency of missed diagnosis: A retrospective analysis of postmortem examination data.

PURPOSE: The present study was conducted to explore the impact of computed tomographic (CT) scanning on the diagnostic discrepancy rate. MATERIALS AND METHODS: This single-center, retrospective study reviewed postmortem examination results, clinical diagnoses, and radiologic imaging data for patients admitted to the intensive care unit (ICU) in 2008 to 2013. The Goldman criteria were used to classify diagnostic discrepancies. RESULTS: The data of 577 patients who died during their ICU stay were retrieved. The postmortem examination rate was 42.9% (n=248). Significant diagnostic discrepancies (Goldman I and II) were recorded in 24 cases (9.7%). The postmortem examination rate decreased significantly from the first half (n=143; 51.1%) to the second half (n=105; 35.4%) of the study period (P<.0001). Among those with postmortem examinations, the use of antemortem body CT scans increased significantly from the first half (n=59; 41.3%) to the second half (n=64; 51.0%; P=.002) of the study period. The significant diagnostic discrepancy rate did not change with time (8.4% vs 11.4%, respectively; P=.424). CONCLUSION: The postmortem examination rate has decreased, whereas antemortem CT scans has increased.

Contributing factors in self-poisoning leading to hospital admission in adolescents in northern Finland.

AIM: To evaluate the frequencies of different agents used in self-poisonings and acute factors contributing to intoxication of patients aged 12-18 years in northern Finland. MATERIAL: Retrospective medical record review of all hospitalized patients during the period from January 1, 1991 to December 31, 2006. OUTCOME MEASURES: Cause of the admission, contributing factors, readmissions within one year. RESULTS: There were 309 admissions during the period, 54% were females. The leading cause of admission was alcohol, in 222 cases (71.8%). Hospitalizations related to alcohol consumption were associated with accidental poisoning in recreational use. There were no acute contributing factors in the majority of all patients. Over one-third of all intoxications were intentional self-harm, although previously diagnosed psychiatric diseases were rare. CONCLUSIONS: It is crucial to recognize adolescent psychiatric disorders in time and consult child and adolescent psychiatrist in case of poisoning.