Organ System Dysfunction Research Articles

IMPACT probability of poor outcome and plasma cytokine concentrations are associated with multiple organ dysfunction syndrome following traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Multiple organ dysfunction syndrome (MODS) occurs frequently after TBI and independently worsens outcome. The present study aimed to identify potential admission characteristics associated with post-TBI MODS. The authors performed a secondary analysis of a recent randomized clinical trial studying the effects of erythropoietin and blood transfusion threshold on neurological recovery after TBI. Admission clinical, demographic, laboratory, and imaging parameters were used in a multivariable Cox regression analysis to identify independent risk factors for MODS following TBI, defined as maximum total Sequential Organ Failure Assessment (SOFA) score > 7 within 10 days of TBI. Two hundred patients were initially recruited and 166 were included in the final analysis. Respiratory dysfunction was the most common nonneurological organ system dysfunction, occurring in 62% of the patients. International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) probability of poor outcome at admission was significantly associated with MODS following TBI (odds ratio [OR] 8.88, 95% confidence interval [CI] 1.94-42.68, p < 0.05). However, more commonly used measures of TBI severity, such as the Glasgow Coma Scale, Injury Severity Scale, and Marshall classification, were not associated with post-TBI MODS. In addition, initial plasma concentrations of interleukin (IL)-6, IL-8, and IL-10 were significantly associated with the development of MODS (OR 1.47, 95% CI 1.20-1.80, p < 0.001 for IL-6; OR 1.26, 95% CI 1.01-1.58, p = 0.042 for IL-8; OR 1.77, 95% CI 1.24-2.53, p = 0.002 for IL-10) as well as individual organ dysfunction (SOFA component score ≥ 1). Finally, MODS following TBI was significantly associated with mortality (OR 5.95, 95% CI 2.18-19.14, p = 0.001), and SOFA score was significantly associated with poor outcome at 6 months (Glasgow Outcome Scale score < 4) when analyzed as a continuous variable (OR 1.21, 95% CI 1.06-1.40, p = 0.006). Admission IMPACT probability of poor outcome and initial plasma concentrations of IL-6, IL-8, and IL-10 were associated with MODS following TBI.

Results of the Phase 3 VITAL Study of NEOD001 (Birtamimab) Plus Standard of Care in Patients with Light Chain (AL) Amyloidosis Suggest Survival Benefit for Mayo Stage IV Patients

Results of the Phase 3 VITAL Study of NEOD001 (Birtamimab) Plus Standard of Care in Patients with Light Chain (AL) Amyloidosis Suggest Survival Benefit for Mayo Stage IV Patients

Physician Judgment and Circulating Biomarkers Predict 28-Day Mortality in Emergency Department Patients.

To determine whether biomarkers of endothelial activation and inflammation provide added value for prediction of in-hospital mortality within 28 days when combined with physician judgment in critically ill emergency department patients. Prospective, observational study. Two urban, academic emergency departments, with ≈80,000 combined annual visits, between June 2016 and December 2017. Admitted patients, greater than 17 years old, with two systemic inflammatory response syndrome criteria and organ dysfunction, systolic blood pressure less than 90 mm Hg, or lactate greater than 4.0 mmol/L. Patients with trauma, intracranial hemorrhage known prior to arrival, or without available blood samples were excluded. Emergency department physicians reported likelihood of in-hospital mortality (0-100%) by survey at hospital admission. Remnant EDTA blood samples, drawn during the emergency department stay, were used to measure angiopoietin-1, angiopoietin-2, tumor necrosis factor receptor-1, interleukin-6, and interleukin-8. We screened 421 patients and enrolled 314. The primary outcome of in-hospital mortality within 28 days occurred in 31 (9.9%). When predicting the primary outcome, the best biomarker model included angiopoietin-2 and interleukin-6 and performed moderately well (area under the curve, 0.72; 95% CI, 0.69-0.75), as did physician judgment (area under the curve, 0.78; 95% CI, 0.74-0.82). Combining physician judgment and biomarker models improved performance (area under the curve, 0.85; 95% CI, 0.82-0.87), with area under the curve change of 0.06 (95% CI, 0.04-0.09; p < 0.01) compared with physician judgment alone. Predicting in-hospital mortality within 28 days among critically ill emergency department patients may be improved by including biomarkers of endothelial activation and inflammation in combination with emergency department physician judgment.

Autonomic dysfunction following traumatic brain injury: translational insights.

Although there is a substantial amount of research on the neurological consequences of traumatic brain injury (TBI), there is a knowledge gap regarding the relationship between TBI and the pathophysiology of organ system dysfunction and autonomic dysregulation. In particular, the mechanisms or incidences of renal or cardiac complications after TBI are mostly unknown. Autonomic dysfunction following TBI exacerbates secondary injury and may contribute to nonneurologial complications that prolong hospital length of stay. Gaining insights into the mechanisms of autonomic dysfunction can guide advancements in monitoring and treatment paradigms to improve acute survival and long-term prognosis of TBI patients. In this paper, the authors will review the literature on autonomic dysfunction after TBI and possible mechanisms of paroxysmal sympathetic hyperactivity. Specifically, they will discuss the link among the brain, heart, and kidneys and review data to direct future research on and interventions for TBI-induced autonomic dysfunction.

Neurobehavioral outcomes in patients with myelomeningocele.

This paper describes some of the more common patterns in neurobehavioral deficits and their underlying neuroanatomical basis in myelomeningocele (MMC). Patients with MMC can face a lifetime of specific organ system dysfunction, chief among them spinal cord malformations, orthopedic issues, hydrocephalus, and urological disabilities. In addition, patients can experience specific patterns of neurobehavioral difficulties due to the changes in neuroanatomy associated with the open spinal defect. Although there is variability in these patterns, some trends have been described among MMC patients. It is thought that early recognition of these potential neurobehavioral deficits by treating neurosurgeons and other members of the treatment team could lead to earlier intervention and positively impact the overall outcome for patients. Neurodevelopmental and neurobehavioral follow-up assessments are recommended to help guide planning for relevant treatments or accommodations.

Targeting the mTOR pathway in idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic illness of systemic inflammation and organ dysfunction, with unknown etiology. Although therapies targeting IL-6 have been proven effective, a subset of patients with iMCD are resistant to this approach. In this issue of the JCI, Fajgenbaum et al. performed an in-depth analysis of serum inflammatory markers in three iMCD patients refractory to IL-6 blockade, and identified activation of the mTOR pathway associated with symptom flares. Treatment with sirolimus, an mTOR inhibitor, induced remission in all three patients. This study models a precision medicine approach to discovering therapies for rare diseases.

The impact of the systemic inflammatory response on hepatic bacterial elimination in experimental abdominal sepsis

BackgroundBacterial translocation from the gut has been suggested to induce a systemic inflammatory response syndrome (SIRS) and organ dysfunction. The liver has a pivotal role in eliminating circulating bacteria entering from the gut. We investigated whether pre-existing inflammation affects hepatic bacterial elimination.MethodsFifteen anaesthetised piglets were infused with E. coli in the portal vein for 3 h. The naive group (n = 6) received the bacterial infusion without endotoxin exposure. SIRS (SIRS group, n = 6) was induced by endotoxin infusion 24 h before the bacterial infusion. For effects of anaesthesia, controls (n = 3) received saline instead of endotoxin for 24 h. Bacterial counts and endotoxin levels in the portal and hepatic veins were analysed during bacterial infusion.ResultsThe bacterial killing rate was higher in the naive group compared with the SIRS group (p = 0.001). The ratio of hepatic to portal venous bacterial counts, i.e. the median bacterial influx from the splanchnic circulation, was 0.06 (IQR 0.01–0.11) in the naive group and 0.71 (0.03–1.77) in the SIRS group at 3 h, and a magnitude lower in the naive group during bacteraemia (p = 0.03). Similar results were seen for hepatic endotoxin elimination. Peak log tumour necrosis factor alpha was higher in the naive 4.84 (4.77–4.89) vs. the SIRS group 3.27 (3.26–3.32) mg/L (p < 0.001).ConclusionsOur results suggest that hepatic bacterial and endotoxin elimination is impaired in pigs with pre-existing SIRS while the inflammatory response to bacterial infusion is diminished. If similar mechanisms operate in human critical illness, the hepatic elimination of bacteria from the gut could be impaired by SIRS.

Severe maternal morbidity among women with a history of cesarean section at a tertiary referral teaching hospital in the southeast of Iran

ObjectivesAlthough the cesarean section (C-section) is known as a lifesaving procedure, it can also increase the risk of maternal mortality and morbidity. This study was conducted to achieve two objectives: (1) determination of maternal near miss (MNM) indicators and pregnancy outcomes among women with a history of C-section and (2) investigation of the women's experience of near miss events during childbirth to provide a deeper understanding of the weaknesses of care delivery process. Study designThe present study was conducted using a prospective cross-sectional study using the World Health Organization (organ system dysfunction–based) criteria. MethodsAll subjects were women at more than 22 weeks of gestation who gave birth in Ali ibn Abi Talib Hospital, Zahedan, Iran, and were referred to this hospital for childbirth or those within 42 days of pregnancy termination. Logistic regression was used to predict the risk factors for severe maternal outcomes (SMOs). ResultsNearly 58% of all MNM cases were related to women with a history of C-section. The MNM ratio was estimated at 8.04 per 1000 live births. Moreover, the frequent causes of SMOs were reported as severe hemorrhage (58.3%), severe pre-eclampsia/eclampsia (27.8%), medical condition (8.3%), and sepsis or severe systemic infection (5.6%). Abnormally invasive placenta (61%) was the most common cause of severe hemorrhage. After adjustment for potential confounder variables, the hemoglobin level of <11 g/dl (odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.09–0.36) and place of residence (OR = 0.41, 95% CI = 0.19–0.90) remained as independent risk factors for SMOs in the final model of multivariate analysis. ConclusionA risk assessment system is needed to diagnose and manage the risk factors for SMOs during prenatal care. In addition, there should be a continuous audit of the indication and number of C-sections performed across health facilities.

Profile of crizanlizumab and its potential in the prevention of pain crises in sickle cell disease: evidence to date.

Sickle cell disease (SCD) is one of the most common inherited blood disorders globally. It is a grouping of autosomal recessive genetic disorders identified by a genetic mutation that replaces glutamic acid with valine at the sixth amino acid on the hemoglobin β-globin chain. Millions of people around the world live with a severe genotype of SCD that is often associated with occlusion of the microvasculature resulting in episodes of severe pain and multiple organ system dysfunction. These episodes, commonly categorized as vaso-occlusive crises (VOC), are a distinctive clinical presentation of SCD which represents the majority of SCD morbidity and associated hospitalizations. Though the complete process by which these crises occur is complex and not fully outlined, evidence reveals this process to be multifactorial and heterocellular. For nearly two decades, hydroxyurea was the only FDA-approved therapy for SCD. Evidence to date shows that hydroxyurea treatment significantly reduces the rate of VOC, hospitalizations, and mortality. Despite these benefits, adherence remains problematic due to a variety of adverse effects and interpatient variability connected with hydroxyurea therapy. Crizanlizumab, an adhesion inhibitor of sickled red blood cells, was recently granted breakthrough therapy designation. Results of a phase 2 study have reported a successful reduction in annual rates of vaso-occlusive crisis with a favorable safety profile. This paper reviews the available literature concerning crizanlizumab use in patients with SCD.

Interleukin-6 improves infection identification when added to physician judgment during evaluation of potentially septic patients

BackgroundIdentifying infection is critical in early sepsis screening. This study assessed whether biomarkers of endothelial activation and/or inflammation could improve identification of infection among Emergency Department (ED) patients with organ dysfunction. MethodsWe performed a prospective, observational study at two urban, academic EDs, between June 2016 and December 2017. We included admitted adults with 1) two systemic inflammatory response syndrome criteria and organ dysfunction, 2) systolic blood pressure < 90 mmHg, or 3) lactate ≥4.0 mmol/L. We excluded patients with trauma, transferred for intracranial hemorrhage, or without available blood samples. Treating ED physicians reported presence of infection (yes/no) at inpatient admission. Assays for angiopoietin-1, angiopoietin-2, soluble tumor necrosis factor receptor-1, interleukin-6, and interleukin-8 were performed using ED blood samples. The primary outcome was infection, adjudicated by paired physician review. Using logistic regression, we compared the performance of physician judgment, biomarkers, and physician judgment-biomarkers combination to predict infection. Area under the curve (AUC) and AUC 95% confidence intervals were estimated by bootstrap procedure. ResultsOf 421 patients enrolled, 306 patients met final study criteria. Of these, 154(50.3%) patients had infectious etiologies. Physicians correctly discriminated infectious from non-infectious etiologies in 239 (78.1%). Physician judgment performed moderately when discriminating infection (AUC 0.78, 95% CI: 0.74–0.82) and outperformed the best biomarker model, interleukin-6 alone, (AUC 0.71, 0.66–0.76). Physician judgment improved when including interleukin-6 (AUC 0.84, 0.79–0.87), with modest AUC improvement: 0.06 (0.03–0.08). ConclusionsIn ED patients with organ dysfunction, plasma interleukin-6 may improve infection discrimination when added to physician judgment.

Buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children.

Fluid therapy is one of the main interventions provided for critically ill patients, although there is no general consensus regarding the type of solution. Among crystalloid solutions, 0.9% saline is the most commonly administered. Buffered solutions may offer some theoretical advantages (less metabolic acidosis, less electrolyte disturbance), but the clinical relevance of these remains unknown. To assess the effects of buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children. We searched the following databases to July 2018: CENTRAL, MEDLINE, Embase, CINAHL, and four trials registers. We checked references, conducted backward and forward citation searching of relevant articles, and contacted study authors to identify additional studies. We imposed no language restrictions. We included randomized controlled trials (RCTs) with parallel or cross-over design examining buffered solutions versus intravenous 0.9% saline in a critical care setting (resuscitation or maintenance). We included studies on participants with critical illness (including trauma and burns) or undergoing emergency surgery during critical illness who required intravenous fluid therapy. We included studies of adults and children. We included studies with more than two arms if they fulfilled all of our inclusion criteria. We excluded studies performed in persons undergoing elective surgery and studies with multiple interventions in the same arm. We used Cochrane's standard methodological procedures. We assessed our intervention effects using random-effects models, but when one or two trials contributed to 75% of randomized participants, we used fixed-effect models. We reported outcomes with 95% confidence intervals(CIs). We included 21 RCTs (20,213 participants) and identified three ongoing studies. Three RCTs contributed 19,054 participants (94.2%). Four RCTs (402 participants) were conducted among children with severe dehydration and dengue shock syndrome. Fourteen trials reported results on mortality, and nine reported on acute renal injury. Sixteen included trials were conducted in adults, four in the paediatric population, and one trial limited neither minimum or maximum age as an inclusion criterion. Eight studies involving 19,218 participants were rated as high methodological quality (trials with overall low risk of bias according to the domains: allocation concealment, blinding of participants/assessors, incomplete outcome data, and selective reporting), and in the remaining trials, some form of bias was introduced or could not be ruled out.We found noevidence of an effect of buffered solutions on in-hospital mortality (odds ratio (OR) 0.91, 95% CI 0.83 to 1.01; 19,664 participants; 14 studies; high-certainty evidence). Based on a mortality rate of 119 per 1000, buffered solutions could reduce mortality by 21 per 1000 or could increase mortality by 1 per 1000. Similarly, we found no evidence of an effect of buffered solutions on acute renal injury (OR 0.92, 95% CI 0.84to 1.00; 18,701 participants; 9 studies; low-certainty evidence). Based on a rate of 121 per 1000, buffered solutions could reduce the rate of acute renal injuryby 19per 1000, or result in no difference in the rate of acute renal injury. Buffered solutions did not show an effect on organ system dysfunction (OR 0.80, 95% CI 0.40 to 1.61; 266 participants; 5 studies; very low-certainty evidence). Evidence on the effects of buffered solutions on electrolyte disturbances varied: potassium (mean difference (MD) 0.09, 95% CI -0.10 to 0.27; 158 participants; 4 studies; very low-certainty evidence); chloride (MD -3.02, 95% CI -5.24 to -0.80; 351 participants; 7 studies; very low-certainty evidence); pH (MD 0.04, 95% CI 0.02 to 0.06; 200participants; 3 studies; very low-certainty evidence); and bicarbonate (MD 2.26, 95% CI 1.25 to 3.27; 344 participants; 6 studies; very low-certainty evidence). We found no effect of buffered solutions on preventing in-hospital mortality compared to 0.9% saline solutions in critically ill patients. The certainty of evidence for this finding was high, indicating that further research would detectlittle or no difference in mortality.The effects of buffered solutions and 0.9% saline solutions on preventing acute kidney injury were similar in this setting. The certainty of evidence for this finding was low, and further research could change this conclusion. Patients treated with buffered solutions showed lower chloride levels, higher levels of bicarbonate, and higher pH. The certainty of evidence for these findings was very low. Future research should further examine patient-centred outcomes such as quality of life. The three ongoing studies once published and assessed may alter the conclusions of the review.

The MITRA-HR study: design and rationale of a randomised study of MitraClip transcatheter mitral valve repair in patients with severe primary mitral regurgitation eligible for high-risk surgery.

Percutaneous mitral valve repair has become an alternative to conventional surgery in patients suffering primary mitral regurgitation (MR) with a contraindication to surgery and could benefit patients at high surgical risk. The aim of the MITRA-HR study is to raise the level of evidence supporting the use of the MitraClip device in primary MR patients with a predefined high risk for surgery. MITRA-HR is a prospective, multicentre, randomised study designed to compare mitral valve repair using the MitraClip with conventional surgery in patients with severe primary mitral regurgitation at high risk for surgery. The surgical risk is defined by age, Society of Thoracic Surgeons (STS) risk estimate score, frailty, major organ system dysfunction, and procedure-specific impediments. The study will enrol 330 patients randomised between conventional surgery and MitraClip with a 1:1 ratio. The composite primary endpoint includes all-cause mortality, unplanned rehospitalisation for cardiovascular reasons, and mitral valve reintervention at 12 months. The main secondary safety endpoint is a major adverse event composite assessment evaluated 30 days after the procedure. The randomised MITRA-HR study is designed to provide additional supportive evidence of non-inferiority in efficacy and superiority in safety for percutaneous mitral valve repair using the MitraClip compared to conventional surgery in high surgical risk patients.

Diabetes sepsis on Wistar rat strain (Rattus norvegicus) induced by streptozotocin and bacteria Staphylococcus aureus.

Background and Aim:Sepsis is characterized by loss of control of the inflammatory response, which can be triggered by various microorganisms and toxic secretions. The mortality rate increases due to impaired endothelial function caused dysfunctional organ systems. Diabetes is closely related to sepsis. The study aimed to determine the method of using animal models of sepsis diabetes through a combination of streptozotocin (STZ) and Staphylococcus aureus infection based on biological marker parameters.Materials and Methods:A total of 30 male Wistar rats of 2.5-3 months old weighing approximately 150-250 g body weight (BW) divided into six treatment groups with five replications per group were used in the study. Treatment A was negative control (healthy rats) and Treatment B was the positive control (with diabetes) where rats were given STZ dose at 45 mg/kg BW on day 8 intraperitoneally (IP). The blood glucose was measured on day 10, Treatment C was a positive control (bacteria), rats inoculated with S. aureus with a concentration of 108 CFU/mL on day 8 given IP and observed sepsis conditions on day 10th. Treatment group (D, E, and F): Rats given STZ dose at 45 mg/kg BW on day 8th by IP and measured blood glucose on day 10th, then inoculated with S. aureus with different concentrations of 105 CFU/mL, 106 CFU/mL, and 107 CFU/mL on the 10th day, respectively, and were later observed the condition of sepsis on day 12th. Data on diabetes bacteremia were quantitative used blood glucose levels, the bacterial count, and C-reactive protein (CRP) and were analyzed using the one-way analysis of variance test with a confidence level of 95%. Physical examination (temperature and respiration) is qualitative.Results:Physical examination showed that all treatments had a normal temperature, an increased pulse in Groups D, E, and F and a decrease in respiratory rate in the treatment of E and F, the bacteria found in the vital organs in all groups, and CRP levels were not significantly different at all.Conclusion:Animal model of diabetes sepsis can be observed through a combination of pancreas damage, and respiration, the bacteria in the vital organs.

Cytokine clearance with CytoSorb\xae during cardiac surgery: a pilot randomized controlled trial

BackgroundCardiopulmonary bypass (CPB) is often associated with degrees of complex inflammatory response mediated by various cytokines. This response can, in severe cases, lead to systemic hypotension and organ dysfunction. Cytokine removal might therefore improve outcomes of patients undergoing cardiac surgery. CytoSorb® (Cytosorbents, NJ, USA) is a recent device designed to remove cytokine from the blood using haemoadsorption (HA). This trial aims to evaluate the potential of CytoSorb® to decrease peri-operative cytokine levels in cardiac surgery.MethodsWe have conducted a single-centre pilot randomized controlled trial in 30 patients undergoing elective cardiac surgery and deemed at risk of complications. Patients were randomly allocated to either standard of care (n = 15) or CytoSorb® HA (n = 15) during cardiopulmonary bypass (CPB). Our primary outcome was the difference between the two groups in cytokines levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, MCP-1) measured at anaesthesia induction, at the end of CPB, as well as 6 and 24 h post-CPB initiation. In a consecutive subgroup of patients (10 in HA group, 11 in control group), we performed cross-adsorber as well as serial measurements of coagulation factors’ activity (antithrombin, von Willebrand factor, factor II, V, VIII, IX, XI, and XII).ResultsBoth groups were similar in terms of baseline and peri-operative characteristics. CytoSorb® HA during CPB was not associated with an increased incidence of adverse event. The procedure did not result in significant coagulation factors’ adsorption but only some signs of coagulation activation. However, the intervention was associated neither with a decrease in pro- or anti-inflammatory cytokine levels nor with any improvement in relevant clinical outcomes.ConclusionsCytoSorb® HA during CPB was not associated with a decrease in pro- or anti-inflammatory cytokines nor with an improvement in relevant clinical outcomes. The procedure was feasible and safe. Further studies should evaluate the efficacy of CytoSorb® HA in other clinical contexts.Trial registrationClinicalTrials.gov NCT02775123. Registered 17 May 2016.

Non-obstetric causes of severe maternal complications: a secondary analysis of the Nigeria Near-miss and Maternal Death Survey.

To evaluate the burden, causes and outcomes of severe non-obstetric maternal complications in Nigerian public tertiary hospitals. Secondary analysis of a nationwide cross-sectional study. Forty-two tertiary health facilities. Women admitted with complications during pregnancy, childbirth or puerperium. All cases of severe maternal outcome (SMO: maternal near-miss or maternal death) due to non-obstetric causes were prospectively identified over a 1-year period. Maternal near-miss was defined using organ-system dysfunction (WHO), clinical, or management-based criteria. Causes and contributions of non-obstetric complications to SMO; fetal and neonatal outcomes; health service events associated with non-obstetric complications; and mortality index (% of maternal death/SMO). Of 100107 women admitted with complications, 9401 (9.4%) were for non-obstetric causes; and 4.0% (375/9401) suffered severe non-obstetric complications. Of the 375 cases of severe non-obstetric complications, 48.8% (183/375) were near-misses and 51.2% (192/375) were maternal deaths. Severe anaemia unrelated to haemorrhage contributed 61.2% of near-misses and 32.8% of maternal deaths. The highest mortality indices were observed for cancer (91.7%), hepatic diseases (81.8%) and HIV/AIDS/HIV wasting syndrome (80.4%). Fatality was significantly high with extremes of age and no formal education. Regarding organ dysfunctions, neurological (77.1%) and cardiovascular (75.0%) dysfunctions had the highest mortality indices. Perinatal mortality was 65.9%. Time from diagnosis of severe non-obstetric complications to review by senior medical personnel, and to definitive intervention was <30 minutes in 30.2% and 29.8% of women with SMO, respectively. However, over 240 minutes elapsed between diagnosis and definitive intervention in more than one-third of women with SMO. Non-obstetric complications are associated with poorer pregnancy outcomes and deserve attention similar to that accorded obstetric complications. The original research that generated the data for this secondary analysis and the publication of this secondary analysis were funded by the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a co-sponsored programme executed by the World Health Organization (WHO). Non-obstetric causes are important contributors to maternal deaths and life-threatening morbidities in Nigerian hospitals.

Organ system network analysis and biological stability in critically ill patients

BackgroundContinuous coordination among organ systems is necessary to maintain biological stability in humans. Organ system network analysis in addition to organ-oriented medicine is expected to improve patient outcomes. However, organ system networks remain beyond clinical application with little evidence for their importance on homeostatic mechanisms. This proof-of-concept study examined the impact of organ system networks on systemic stability in severely ill patients.MethodsPatients admitted to the intensive care unit of the University of Tokyo Hospital with one representative variable reflecting the condition of each of the respiratory, cardiovascular, renal, hepatic, coagulation, and inflammatory systems were enrolled. Relationships among the condition of individual organ systems, inter-organ connections, and systemic stability were evaluated between non-survivors and survivors whose organ system conditions were matched to those of the non-survivors (matched survivors) as well as between non-survivors and all survivors. We clustered these six organ systems using principal component analysis and compared the dispersion of the principal component scores of each cluster using the Ansari-Bradley test to evaluate systemic stability involving multiple organ systems. Inter-organ connections were evaluated using Spearman’s rank test.ResultsAmong a total of 570 enrolled patients, 91 patients died. The principal component analysis yielded the respiratory-renal-inflammatory and cardiovascular-hepatic-coagulation system clusters. In the respiratory-renal-inflammatory cluster, organ systems were connected in both the survivors and the non-survivors. The principal component scores of the respiratory-renal-inflammatory cluster were dispersed similarly (stable cluster) in the non-survivors, the matched survivors, and the total survivors irrespective of the severity of individual organ system dysfunction. Conversely, in the cardiovascular-hepatic-coagulation cluster, organ systems were connected only in the survivors, and the principal component scores of the cluster were significantly dispersed (unstable cluster) in the non-survivors compared to the total survivors (P = 0.002) and the matched survivors (P = 0.004).ConclusionsThis study demonstrated that systemic instability was closely associated with network disruption among organ systems irrespective of their dysfunction severity. Organ system network analysis is necessary to improve outcomes in severely ill patients.

Continuous intracerebroventricular injection of Porphyromonas gingivalis lipopolysaccharide induces systemic organ dysfunction in a mouse model of Alzheimer's disease.

Systemic organ dysfunction is one of the important issues for the patients with Alzheimer's disease (AD) and their caregivers. Recent evidences suggest that periodontitis is a possible risk factor for progression of AD and lipopolysaccharide derived from Porphyromonas gingivalis (Pg-LPS) which is a major periodontopathic bacteria induces cognitive impairment in mice. However, the precise relationships between the brain exposure of Pg-LPS and systemic organ dysfunction in AD patients are still undetermined. In this study, we investigated whether brain exposure of Pg-LPS induced systemic organ dysfunction in a model of AD mouse. We employed 6 (young) and 13 (middle-aged) months-old 5XFAD mice and 6 months-old littermate (LT) mice, and treated with intracerebroventricular (ICV) injection of 2 μg Pg-LPS or saline (vehicle). The animals were monitored cognitive functions (Y maze, nest building, and Morris water maze tests), motor functions (wire hang and rotarod tests), physical condition (symptom score), and blood pressure (BP). Twenty-eight days later, their organs were weighted and the organ damages were examined. Continuous ICV injection of 2 μg/day Pg-LPS increased ionized calcium binding adapter molecule-1 (Iba-1) and cluster of differentiation 3 (CD3) positive cells in periventricular area of 5XFAD mice without enhancement of cognitive impairment, amyloid β protein deposition, expressions of phosphorylated nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 (COX-2). In addition, the Pg-LPS lowered the latency of rotarod test in young 5XAD mice and also reduced symptom score and weight of gastrocnemius muscle in the middle-aged animals. Moreover, the Pg-LPS induced cardiac atrophy in both young and middle-aged 5XFAD mice, and increased Iba-1 positive cells in left ventricle of the young animals. On the other hand, single ICV injection of 2 μg Pg-LPS in 5XFAD and continuous injection of 2 μg/day Pg-LPS in LT mice did not show any positive findings. Our present results demonstrated that continuous brain exposure of Pg-LPS started sarcopenia and cardiac injury without enhancing cognitive impairment in AD model mice.

Fatal consequences caused by prolonged chloroform inhalation in a child

Introduction. Chloroform intoxication as a result of inhalation is usually associated with occupational exposure. Fatal cases of accidental and intentional chloroform poisoning are extremely rare. The aim of this work was to report a case with fatal consequences caused by prolonged chloroform inhalation in a child. Case outline. We report a case of a three-month-old child found dead by its mother in their home. Investigation provided the data about two refrigerators in the house, which were not entirely functional, and were filled with a refrigerant based on chloroform, and about a recent house spraying with a pesticide also based on chloroform. Forensic autopsy was performed the following day. Autopsy established the existence of malnutrition, dehydration, brain and lungs edema, the presence of very scarce contents in the digestive tract, and the enlargement of the abdominal lymph nodes. The initial stage of liver degeneration was noted on histopathological examination. Chemical-toxicological analysis of organ tissue samples (brain, lungs, spleen, liver with gall bladder, kidney and bladder, stomach, small and large intestine) performed using the techniques of headspace gas chromatography with mass detector, confirmed chloroform poisoning. Conclusion. The emaciation underlying the dysfunction of organ systems provided a grim frame for a child to succumb to chloroform toxicity. The proper use and maintenance of domestic appliances, and careful application of chemical agents indoors is an imperative, especially in the vicinity of children. Low levels of chloroform inhaled from the room air may have fatal consequences in a susceptible individual.

Low tidal volume ventilation strategy and organ functions in patients with pre-existing systemic inflammatory response.

Background and Aims:Ventilation can induce increase in inflammatory mediators that may contribute to systemic organ dysfunction. Ventilation-induced organ dysfunction is likely to be accentuated if there is a pre-existing systemic inflammatory response.Material and Methods:Adult patients suffering from intestinal perforation peritonitis-induced systemic inflammatory response syndrome and scheduled for emergency laparotomy were randomized to receive intraoperative ventilation with 10 ml.kg-1 tidal volume (Group H) versus lower tidal volume of 6 ml.kg-1 along with positive end-expiratory pressure (PEEP) of 10 cmH2O (Group L), (n = 45 each). The primary outcome was postoperative organ dysfunction evaluated using the aggregate Sepsis-related Organ Failure Assessment (SOFA) score. The secondary outcomes were, inflammatory mediators viz. interleukin-6, tumor necrosis factor-α, procalcitonin, and C-reactive protein, assessed prior to (basal) and 1 h after initiation of mechanical ventilation, and 18 h postoperatively.Results:The aggregate SOFA score (3[1–3] vs. 1[1–3]); and that on the first postoperative day (2[1–3] vs. 1[0–3]) were higher for group L as compared to group H (P < 0.05). All inflammatory mediators were statistically similar between both groups at all time intervals (P > 0.05).Conclusions:Mechanical ventilation with low tidal volume of 6 ml/kg-1 along with PEEP of 10 cmH2O is associated with significantly worse postoperative organ functions as compared to high tidal volume of 10 ml.kg-1 in patients of perforation peritonitis-induced systemic inflammation undergoing emergency laparotomy.

The effect of ketamine on the immature granulocyte and C-reactive protein concentration in rat models of sepsis

Background: Sepsis directly affects the immune system, leads tissue damage, and forms system organ dysfunction. The immunological biomarker of sepsis has a possibility to become an immunotherapy target of sepsis. This study was conducted to determine the effect of ketamine on the number of immature granulocyte and C-reactive protein (CRP) concentration in rat models of sepsis. Materials and Methods: This study used thirty white mice (Rattus norvegicus) divided into six treatment groups. The negative control group received nothing, and the positive control (sepsis) group was fecal-induced peritonitis (FIP) by fecal administration (i. p). The treatment groups (A, B, C, and D) treat with ketamine 5 mg/kg body weight (i. p.) right after FIP, 3 h after FIP, 5 h after FIP, and intermittent every 2 h. The peripheral mononuclear blood cell was isolated 6 h after FIP. The immature granulocytes counted using a hematology analyzer while CRP concentration analyzed using kit enzyme-linked immunosorbent assay. Data were analyzed statistically using the one-way ANOVA test using SPSS version 20 software (P < 0.05). Results: Sepsis induction with FIP increases the number of immature granulocytes in animal models from 0.48% to 9.12% (P < 0.05) but did not affect CRP concentration (P > 0.05). The ketamine administration significantly decreases the immature granulocytes in Groups C (1.04%) and D (1.58%). Ketamine administration did not have a significant effect on CRP concentration. Conclusion: The ketamine administration at 5 h after FIP and intermittently every 2 h can be an alternative to be sepsis immunotherapy with immature granulocyte as the potential target.