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Aim: To determine the risk factors affecting the mortality rate and outcomes of patients with subarachnoid hemorrhage (SAH)., Material and Methods: The records of patients who underwent aneurysm treatment and intensive care unit (ICU) followup in our hospital between 2013-2021 were reviewed retrospectively. Demographics of the patients, aneurysm characteristics, complications in the ICU, the Hunt Hess score, Glasgow Coma Scale (GCS), Acute Physiologic Assessment and Chronic Health Evaluation II score (APACHE II), sepsis status, and mechanical ventilation (MV) needed during ICU admission were collected. The generalized linear mixed modeling method was used to determine independent risk factors affecting mortality., Results: The records of 91 patients who met the inclusion criteria were analyzed. The age of the patients ranged from 21 to 86 years, and the female-to-male ratio was 6 / 7, with a mean age of 49.9 ± 13.06 years. The aneurysm treatment modality was surgical in 79 patients (86.8%) and endovascular in 12 patients (13.2%). The length of the ICU stay was mean 10.96 ± 13.66 days. While 64.8% (n=59) of the patients were discharged, 7.7% (n=7) were referred to palliative care units, and 25% (n=25) died. A one-unit increase in the APACHE II score was determined to increase the risk of vasospasm 1.154 times (p < 0.001). Analysis showed that a one-day increase in the MV day increased the mortality risk 1.838 times (p < 0.001), and vasospasm increased the mortality risk 32.151 times (p=0.004) CONCLUSION: The length of hospital stay, the day of MV, and the presence of vasospasm were determined as independent risk factors affecting mortality. Early diagnosis and rapid treatment of vasospasm, which increases mortality during ICU follow-up, positively impact patient outcomes.

Background: Vaccines against coronavirus disease-19 (COVID-19) have been effective in preventing symptomatic diseases, hospitalizations, and intensive care unit (ICU) admissions. However, data regarding the effectiveness of COVID-19 vaccines in reducing mortality among critically ill patients with COVID-19 remains unclear., Aims: To determine the vaccination status and investigate the impact of the COVID-19 vaccine on the 28-day mortality in critically ill patients with COVID-19., Study Design: Multicenter prospective observational clinical study., Methods: This study was conducted in 60 hospitals with ICUs managing critically ill patients with COVID-19. Patients aged ≥ 18 years with confirmed COVID-19 who were admitted to the ICU were included. The present study had two phases. The first phase was designed as a one-day point prevalence study, and demographic and clinical findings were evaluated. In the second phase, the 28-day mortality was evaluated., Results: As of August 11, 2021, 921 patients were enrolled in the study. The mean age of the patients was 65.42 ± 16.74 years, and 48.6% (n = 448) were female. Among the critically ill patients with COVID-19, 52.6% (n = 484) were unvaccinated, 7.7% (n = 71) were incompletely vaccinated, and 39.8% (n = 366) were fully vaccinated. A subgroup analysis of 817 patients who were unvaccinated (n = 484) or who had received two doses of the CoronaVac vaccine (n = 333) was performed. The 28-day mortality rate was 56.8% (n = 275) and 57.4% (n = 191) in the unvaccinated and two-dose CoronaVac groups, respectively. The 28-day mortality was associated with age, hypertension, the number of comorbidities, type of respiratory support, and APACHE II and sequential organ failure assessment scores ( p < 0.05). The odds ratio for the 28-day mortality among those who had received two doses of CoronaVac was 0.591 (95% confidence interval: 0.413-0.848) ( p = 0.004)., Conclusion: Vaccination with at least two doses of CoronaVac within six months significantly decreased mortality in vaccinated patients than in unvaccinated patients.

Background: The difficulties in the identification of C. auris and the delays in the implementation of infection control precautions contribute to outbreaks. This study analyzed 10 patients with COVID-19 and C. auris candidemia, their characteristic and clinical features and phylogenetic features, and the antifungal susceptibilities of the isolates., Method: C. auris were detected in the COVID-19 ICU of a university hospital between January and August 2021. Identification to species level was performed using MALDI-TOF MS. Antifungal susceptibilities were determined by the Sensititre YeastOne YO10 panel. The isolates were whole genome sequenced to assess genetic relatedness and a phylogenetic tree was drawn including various C. auris clades., Results: The mean growth time in blood cultures was 38.8 h. C. auris candidemia developed on the average 27th day of ICU admission. All were susceptible to anidulafungin and micafungin, while they were resistant to fluconazole and amphotericin B. Only three isolates were found to be resistant to caspofungin. All patients died. With the WGS method, all isolates were found in a close resemblance to each other in terms of total nucleotide similarity (with a minimum of 96% pairwise alignment). Our isolates showed the closest similarity to South Asian clade (Clade I)., Conclusions: This study is the first to evaluate the phylogenetic characteristics of C. auris using WGS and to determine antifungal susceptibilities in Türkiye on COVID-19 patients. The mortality rate was very high in patients who have both COVID-19 and C. auris candidemia., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Sepsis, defined as an increase of 2 points or more in the sequential organ failure assessment score, is a life-threatening organ dysfunction caused by the dysregulated host response to infection. Volume-conductivity-scatter (VCS) parameters of cell counters which are known as cell population data (CPD) have been suggested to be beneficial in diagnosing sepsis. We aimed to evaluate the diagnostic value of CPD parameters in sepsis in comparison to nonsystemic infection cases (NSI) and non-infectious acute and chronic inflammatory conditions., Materials and Methods: We prospectively included four groups of patients" data: sepsis (n = 66), localized infection (pneumonia, n = 59), chronic inflammation (rheumatoid arthritis, n = 92) and noninfectious inflammation (coronary artery bypass graft operation, n = 56) groups, according to their clinical status and laboratory results. Samples for cell counting and serum markers were collected on the same day of culture collection. VCS parameters were measured by Unicel DxH800 Coulter Cellular Analyzer (Beckman Coulter, USA)., Results: Mean neutrophil volume (MN-V-NE), was highest in the sepsis group [155(149-168)] compared to the localized infection [148(140-158)], chronic inflammation [144.5(142-149)] and noninfectious inflammation [149(145.2-153.7)] (P = 0.001, P < 0.001, P < 0.001, respectively). Neutrophil volume SD (SD-V-NE) was higher in the sepsis [21(18.8-23.7)], significantly differentiating sepsis from other groups. The area under curves of procalcitonin and hs-C-reactive protein were 0.846 and 0.837, respectively, in the receiver-operating characteristic curves (ROC) . CPD combinations, (SD-V NE + SD-V LY + SD-V MO), (SD-V NE + SD-V MO), and (MN-V NE + SD-V NE + SD-C LY + SD-V MO) had greater AUC values than procalcitonin's., Conclusion: VCS parameters might be promising for differentiating sepsis and non-sepsis cases. Additionally, obtaining these data routinely makes their prospects promising without any additional cost and time.

This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered via jet nebulizer. Patients received 1-5x10 10 nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) [20.8% (P < 0.05)], oxygen saturation (SpO 2 ) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO 2 /FiO 2 ) [127.9% (P < 0.05)] that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gül, Gonen, Jones, Taşlı, Zararsız, Ünal, Özdarendeli, Şahin, Eken, Yılmaz, Karakukçu, Kırbaş, Gökdemir, Bozkurt, Özkul, Oktay, Uygut, Cinel and Çetin.)

Aim: New coronavirus disease (COVID-19) has become an international emergency. As many of the intensive care unit (ICU) patients with the disease also present multiple organ failure, blood purification techniques might be a good choice in their treatment. In this study we aimed to investigate the role of cytokine removal in COVID-19 patients managed in ICUs. Methods: For this case-control study we have investigated the role of the cytokine removal by means of two resin membranes (HA330 and Mediasorb) in COVID-19 patients managed in ICUs. Particularly, we investigated the overtime variation in clinical severity scores, laboratory variables, and effects on hospital and ICU stay and mortality. Results: Seventy-two patients have been evaluated, of which half constituted Cytokine Filtration (CF) Group, and other half the Case-Control (CC) Group. Mortality was 55.6% and 50% in CF and CC groups, respectively. In the CF Group, there was decrease in C-reactive protein (CRP) and fibrinogen levels measured at the end of cytokine adsorption; lymphocyte count and ratio were increased, whereas neutrophile ratio was decreased. There were no differences between the groups regarding other laboratory variables, SOFA scores and vasopressor uses. Conclusions: We have demonstrated decrease in CRP, fibrinogen and increase in lymphocyte count in the patients having cytokine adsorption, but there was no clinical reflection of these benefits, and no decrease in mortality as well. Even though there is physio-pathologic rationale to use cytokine adsorption techniques for immunomodulation in critically ill COVID-19 patients, it is early to make strong suggestions about their benefits.

Introduction: Healthcare-associated infection is an important cause of mortality and morbidity worldwide. Well-regulated infection control and hand hygiene are the most effective methods for preventing healthcare-associated infections. This study evaluated and compared conventional hand hygiene observation and an electronic hand-hygiene recording and reminder system for preventing healthcare-associated infections., Methodology: This pre- and post-intervention study, employed an electronic hand-hygiene recording and reminder system for preventing healthcare-associated infections at a tertiary referral center. Healthcare-associated infection surveillance was recorded in an anesthesia and reanimation intensive care unit from April 2016 to August 2016. Hand-hygiene compliance was observed by conventional observation and an electronic recording and reminder system in two consecutive 2-month periods. healthcare-associated infections were calculated as incidence rate ratios., Results: The rate of healthcare-associated infections in the electronic hand- hygiene recording and reminder system period was significantly decreased compared with that in the conventional hand-hygiene observation period (incidence rate ratio = 0.58; 95% confident interval = 0.33-0.98). Additionally, the rate of central line-associated bloodstream infections and the rate of ventilator-associated pneumonia were lower during the electronic hand hygiene recording and reminder system period (incidence rate ratio= 0.41; 95% confident interval = 0.11-1.30 and incidence rate ratio = 0.67; 95% confident interval = 0.30-1.45, respectively)., Conclusions: After implementing the electronic hand hygiene recording and reminder system, we observed a significant decrease in healthcare-associated infections and invasive device-associated infections. These results were encouraging and suggested that electronic hand hygiene reminder and recording systems may reduce some types of healthcare-associated infections in healthcare settings., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Gulsen Akkoc, Ahmet Soysal, Fethi Gul, Eda Kepenekli Kadayifci, Mustafa Kemal Arslantas, Nurhayat Yakut, Beliz Bilgili, Sevliya Ocal Demir, Murat Haliloglu, Umut Kasapoglu, Ismail Cinel.)

Background: We report a nosocomial outbreak caused by Burkholderia cepacia that occurred among six patients admitted in the medical and surgical intensive care unit between 04 March 2019 and 02 April 2019 in Istanbul, Turkey., Methods: The outbreak investigation was launched on 11 March 2019 five days after the detection of B. cepacia in four different patients. We defined potential reservoirs and started environmental screening. We sampled the liquid solutions used in patient care activities. Pulse-field gel electrophoresis (PFGE) was performed to determine the genetic relatedness of environmental and patient samples., Results: Burkholderia cepacia was isolated in tracheal aspiration cultures of six patients. Three out of six patients developed healthcare-associated pneumoniae due to B. cepacia. Environmental cultures in the ICUs revealed B. cepacia growth in 2% chlorhexidine-gluconate mouthwash solution that been used in the colonized patients as well as in samples obtained from the unused products. PFGE revealed the patient and a specific batch of chlorhexidine mouthwash solution samples had a 96% similarity., Conclusion: Contamination of medical solutions used in critical patient care could cause outbreaks and should be detected early by infection control teams., (© 2021. The Author(s).)

Background: Pre-existing chronic liver disease is currently considered a poor prognostic factor for coronavirus disease 2019 (COVID-19). The present study aimed to investigate the association of liver stiffness measurement (LSM) with disease severity and clinical course of COVID-19., Methods: We prospectively recruited consecutive hospitalised adult patients with COVID-19 in a 3-month period. Demographic, laboratory, clinical and vibration-controlled transient elastography (VCTE) features were recorded at entry, and all patients were prospectively followed-up. Severe liver fibrosis was defined as an LSM value higher than 9.6 kPA. Multivariate logistic regression analysis was performed to reveal factors associated with disease severity and outcomes., Results: Out of 98 eligible patients with COVID-19, 12 (12.2%) had severe liver fibrosis. Patients with severe liver fibrosis had higher baseline disease severity (P = .022), more commonly required oxygen treatment at entry (P = .010), and had intensive-care unit (ICU) requirements during the 6 (1-39)-day median follow-up time (P = .017). The presence of severe liver fibrosis was independently associated with disease severity (odds ratio (OR): 7.685, 95% confidence interval (CI): 1.435-41.162, P = .017) and ICU requirement (OR: 46.656, 95% CI: 2.144-1015.090, P = .014). LSM was correlated with alanine aminotransferase levels (P = .005, r: 0.283), but not with other markers of acute hepatic injury or inflammation., Conclusion: Initial VCTE application might help physicians identify patients who are more likely to have severe illness or worse clinical outcomes, in addition to other well-established clinical and laboratory factors. Further multicentre prospective studies are warranted to validate our results., (© 2021 John Wiley & Sons Ltd.)

Oropharyngeal dysphagia is one of the complications of endotracheal intubation. As expected, cases of dysphagia following coronavirus disease 2019 (COVID-19) reported to date have all been intubated. We here report a case of sarcopenic dysphagia following severe COVID-19 pneumonia in a nonintubated older adult. The patient was an 85-year-old male who was readmitted to the hospital with dysphagia and subsequent aspiration pneumonia in the first week after his discharge from the COVID-19 unit. On physical examination, the patient was sarcopenic and malnourished. Flexible endoscopic evaluation of swallowing (FEES) revealed aspiration into the airway. Enteral feeding was initiated and the infusion rate gradually increased to achieve the desired protein-energy targets. Control FEES 2 months after discharge showed recovery of swallowing function, with no apparent penetration or aspiration. Clinicians caring for patients with COVID-19 should be aware that dysphagia, which is associated with increased mortality in older adults, may occur even in the absence of intubation. We recommend that the evaluation of dysphagia be part of the clinical assessment in older COVID-19 patients with malnutrition or sarcopenia., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Background: We investigated whether cardiopulmonary bypass (CPB) related oxidative stress mediated glycocalyx degradation can cause an increase in renal resistive index (RRI) or postoperative AKI. Additionally, to evaluate whether RRI and early postoperative serum cystatin C levels could improve the prediction sensitivity of acute kidney injury (AKI)., Methods: Forty-two patients undergoing cardiac surgery were included in this prospective observational study. RRI was measured pre-operatively and in the cardiac intensive care unit. Blood samples were collected for analyzing of cellular injury biomarkers at preoperative and postoperative second hours. We determined areas under the receiver operating characteristic curve (AUC) and odds ratios for postoperative biomarkers and RRI to predict AKI., Results: While postoperative cystatin C level (AUC: 0.902, 95% CI = 0.79-1.00, p  < .001) and RRI (AUC: 0.748, 95% CI = 0.56-0.93, p  = .023) have diagnostic and predictive value in the prediction of AKI, we could not identify any relation between products of oxidative stress and the glycocalyx degradation and AKI., Conclusion: These data suggest that CPB leads to structural and oxidative changes at the protein level and the integrity of glycocalyx is disturbing, but these changes are not specific to kidney injury. Our data suggest that serum cystatin C level and RRI could be used as an early biomarker for postoperative AKI after cardiac surgery.

Introduction: The Clinical Pulmonary Infection Score (CPIS) based on chest X-ray has been developed to facilitate clinical diagnosis of ventilator-associated pneumonia (VAP); however, this scoring system has a low diagnostic performance. We developed the Lung Ultrasound and Pentraxin-3 Pulmonary Infection Score (LUPPIS) for early diagnosis of VAP and evaluated the performance of this new scoring system., Material and Methods: In a prospective study of 78 patients with suspected VAP, we assessed the detection accuracy of LUPPIS for pneumonia in adult patients. We also evaluated the diagnostic performance of pentraxin-3 (PTX-3) findings of infection. On the day of the study, lung ultrasound was performed, PTX-3 levels were determined, and an endotracheal aspirate was obtained for Gram staining and culture., Results: No significant differences were found between groups with respect to age, mechanical ventilation time, APACHE II score, or SOFA score ( p > 0.05). Procalcitonin and PTX-3 levels were significantly higher in the VAP (+) group ( p < 0.001 and p < 0.001, respectively). The threshold for LUPPIS in differentiating VAP (+) patients from VAP (-) patients was > 7. In predicting VAP, LUPPIS > 7 (sensitivity of 84%, specificity of 87.7%) was superior to CPIS > 6 (sensitivity of 40.1%, specificity of 84.5%)., Conclusions: LUPPIS appears to provide better results in the prediction of VAP compared to CPIS, and the importance of lung ultrasound and PTX-3 is emphasized, which is a distinctive property of LUPPIS., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

Background: Mesenchymal stem cells may be used for the treatment of sepsis. Dental follicle stem cells (DFSCs) are easily accessible but have not been studied in vivo or in clinical trials in sepsis models., Aim of the Study: We aim to elucidate DFSC effects on host immunological functions in a rat cecal ligation and perforation (CLP) sepsis model., Methods: Adult male rats were categorized into group 1 (sham procedure SP), group 2 (SP + 1 × 10 6 DFSCs administered 0 h after SP), group 3 (CLP + saline), group 4 (CLP + 1 × 10 6 DFSCs administered 0 h after CLP), and group 5 (CLP + 1 × 10 6 DFSCs administered 4 h after CLP). Green fluorescent protein-labeled cells were used for imaging. Histopathological examination of ileal tissues was performed., Results: A significant increase in the percentage of CD4+/CD25+/Foxp3+ Treg cells in groups 4 and 5 occurred compared with that in group 3. No significant changes in CD3+/CD4+ helper T-cells and CD3+/CD8+ cytotoxic T-cells were observed. Treatment with DFSCs at 4 h significantly decreased the level of TNF-α compared with that in group 3. No significant changes in IL-10 levels and lymphocyte proliferation suppression were observed. During histopathological examination, no high scoring (Chiu scores: 3 or 4) rats were observed in the curative treatment group (group 5)., Conclusions: Treatment with DFSC after 4 h of sepsis induction downregulates tissue inflammatory responses by decreasing TNF-α levels and increasing Treg cell ratio. This also has a protective effect on intestinal tissues during sepsis., (Copyright © 2020 IMSS. Published by Elsevier Inc. All rights reserved.)

Taking into consideration the multisystemic clinical and autopsy findings in "severe" coronavirus disease 2019 patients, viral sepsis would be a more accurate term to describe the whole clinical picture. The most significant pathophysiological components of this picture are intense cytokine release, prolonged inflammation, immunosuppression with T cell exhaustion, and the development of organ dysfunctions. Currently, the optimal treatment for severe coronavirus disease 2019 is uncertain. Supportive treatment and immunomodulators have a critical place in the treatment of severe patients until effective antivirals are developed. Interleukin-6 antagonists, one of the immunomodulating agents, appears to be effective in the treatment of cytokine storm, but some patients continue to have severe lymphopenia and immunosuppression. We believe it can be useful as immunomodulator therapy in critical coronavirus disease 2019 patients because of the benefits of immune checkpoint inhibitors in cancer and sepsis patients., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Septic shock is the most severe form of sepsis, characterized by (a) persistent hypotension despite fluid resuscitation and (b) the presence of tissue hypoperfusion. Delays in the diagnosis and initiation of treatment of septic shock is associated with increasing risk for mortality. Early and effective fluid resuscitation and vasopressor administration play a crucial role in maintaining tissue perfusion in septic shock patients. A low diastolic arterial pressure (DAP) correlates with severity of arteriolar vasodilation, compromises left ventricle oxygen supply and can be used for identifying septic shock patients that would potentially benefit from earlier vasopressor therapy. Controversy currently exists as to the balance of fluids and vasopressors to maintain target mean arterial pressure. The aim of this article is to review the rationale for fluid resuscitation and vasopressor therapy and the importance of both mean and diastolic blood pressure during the initial resuscitation of the septic shock. We relate our personal prescription of balancing fluids and vasopressors in the resuscitation of septic shock., Competing Interests: Declaration of Competing Interest The authors have stated explicitly that there are no conflicts of interest in connection with this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Wastewater (WW) carry considerable amount of chemicals that could have mutagenic or cytotoxic effect from hospital discharges to aquatic environment. Our objective was to determinate the possible mutagenic and toxic effects of hospital originated WWs and effectiveness of the wastewater treatment plants (WTP) functions. In the study the mutagenic and cytotoxic potential of three hospitals and influent/effluent of a treatment plant WW collected in Istanbul and was examined using AMES, XTT, and lactate dehydrogenase (LDH) assays. Mutagenic effects were detected at both hospital discharges and advanced biological wastewater plant. We observed no cytotoxic effect in fibroblasts for LDH and XTT assays whereas high cytotoxicity for all samples was found in hepatocytes by XTT assay. According to the results even if advanced technology is used for treatment of WW, mutagenic and cytotoxic effects still remain, and the present technologies need to be further improved.

Objective: Mushroom poisonings can lead to life-threatening organ dysfunctions and neurotoxicity-related encephalopathy. This study aimed to detect increased intracranial pressure by measuring optic nerve sheath diameter (ONSD) ultrasonographically and to determine its association with clinical and laboratory parameters., Methods: In this prospective case-control study, we evaluated the patients aged above 18 years who presented to the emergency department with mushroom poisoning. Vital signs, clinical and laboratory parameters and ONSD of both eyes measured with transocular ultrasound were noted at initial admission and the 24th hour., Results: We measured ONSD in 26 cases with mushroom poisoning and 26 healthy volunteers. Baseline ONSD measurements of the poisoning group were significantly higher than those of the control group (5.94±0.73 vs. 4.11±0.64, p<0.0001). ONSD values significantly regressed at 24th hour compared with the baseline measurements in the poisoning group (5.94±0.73 vs. 5.06±0.56, p<0.001).The ONSD values were significantly higher in patients who had a clinical picture of encephalopathy compared with patients who didn't have (6.05±0.72 vs. 4.36±1.03, p<0.001). No significant deterioration was observed in ammonium levels, hepatic and renal functions of the patients., Conclusion: We detected increased ONSDs in patients with mushroom poisoning compared with those in the control healthy volunteers. Our findings suggest that ONSD, measured by ultrasonography, may be safely and effectively used to diagnose transient encephalopathy associated with neurotoxicity., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (© Copyright 2020 by Turkish Anaesthesiology and Intensive Care Society.)

Background: Intra-abdominal hypertension (IAH) is a frequent cause of acute kidney injury (AKI) among critically ill patients who have risk factors. This study aimed to determine the relation between Abdominal Perfusion Pressure (APP) and AKI showed by the Doppler-based renal resistive index (RRI)., Methods: In this study, 38 patients older than 18 years old who received mechanical ventilation and had risk factors for the development of IAH were prospectively studied. All measurements and parameters were divided into two groups according to renal dysfunction (Group I: RRI <0.72 vs Group II: RRI >0.72)., Results: The mean IAPs were not significant between the groups, 11.5±6.9 mm Hg in Group I (n=35) and 13.5±5.8 in Group II (n=33), respectively. APPs were statistically higher in Group I (81.2±13.6) than Group II (66.4±9.5) (p<0.001). The AUC for the association between APP at RRI >0.72 was 0.802 (p<0.001), with the APP ≤72 mmHg having a sensitivity of the 76% (95% CI 58-89%) and a specificity of 71% (95% CI 54-85%)., Conclusion: Our findings suggest that an APP with a threshold of ≤72 mmHg is associated with a significant increase in renal RRI, which may be predictive of worsening of renal perfusion.

Ancillary tests can be used for the diagnosis of brain death in cases wherein uncertainty exists regarding the neurological examination and apnoea test cannot be performed. Transcranial Doppler ultrasonography (TCD) is a useful, valid, non-invasive, portable, and repeatable ancillary test for the confirmation of brain death. Despite its varying sensitivity and specificity rates with regard to the diagnosis of the brain death, its clinical use has steadily increased in the intensive care unit because of its numerous superior properties. The use of TCD as an ancillary test for the diagnosis of brain death and cerebral circulatory arrest is discussed in the current review., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (© Copyright 2019 by Turkish Anaesthesiology and Intensive Care Society.)

Objectives: We aimed to obtain information about the characteristics of the ICUs in our country via a point prevalence study., Material and Methods: This cross-sectional study was planned by the Respiratory Failure and Intensive Care Assembly of Turkish Thoracic Society. A questionnaire was prepared and invitations were sent from the association's communication channels to reach the whole country. Data were collected through all participating intensivists between the October 26, 2016 at 08:00 and October 27, 2016 at 08:00., Results: Data were collected from the 67 centers. Overall, 76.1% of the ICUs were managed with a closed system. In total, 35.8% (n=24) of ICUs were levels of care (LOC) 2 and 64.2% (n=43) were LOC 3. The median total numbers of ICU beds, LOC 2, and LOC 3 beds were 12 (8-23), 14 (10-25), and 12 (8-20), respectively. The median number of ventilators was 12 (7-21) and that of ventilators with non-invasive ventilation mode was 11 (6-20). The median numbers of patients per physician during day and night were 3.9 (2.3-8) and 13 (9-23), respectively. The median number of patients per nurse was 2.5 (2-3.1); 88.1% of the nurses were certified by national certification corporation., Conclusion: In terms of the number of staff, there is a need for specialist physicians, especially during the night and nurses in our country. It was thought that the number of ICU-certified nurses was comparatively sufficient, yet the target was supposed to be 100% for this rate.

Purpose: The main purpose of this study was to investigate the dynamics of pentraxin 3 (PTX3) compared with procalcitonin (PCT) and C-reactive protein (CRP) in patients with suspicion of ventilator-associated pneumonia (VAP)., Materials and Methods: We designed a nested case-control study. This study was performed in the Surgical Intensive Care Unit of a tertiary care academic university and teaching hospital. Ninety-one adults who were mechanically ventilated for >48 hours were enrolled in the study. VAP diagnosis was established among 28 patients following the 2005 ATS/IDSA guidelines., Results: The median PTX3 plasma level was 2.66 ng/mL in VAP adults compared to 0.25 ng/mL in non-VAP adults ( p < 0.05). Procalcitonin and CRP levels did not significantly differ. Pentraxin 3, with a 2.56 ng/mL breakpoint, had 85% sensitivity, 86% specificity, 75% positive predictive value, and 92.9% negative predictive value for VAP diagnosis (AUC = 0.78)., Conclusions: With the suspicion of VAP, a pentraxin 3 plasma breakpoint of 2.56 ng/mL could contribute to the decision of whether to start antibiotics.

Objective: The identification of bacteraemia in patients with suspected sepsis is crucial for survival. A cheap, fast and reliable biomarker, which can predict the causative pathogen group, may be useful to confirm or exclude the presence of bacteraemia. This study aimed to evaluate the relationship between procalcitonin (PCT) and the causative pathogen in intensive care patients with sepsis and bacteraemia., Methods: Patients with diagnosed sepsis, a positive blood culture and measured serum procalcitonin levels during their intensive care unit stay were included in the study. Demographic data, PCT level, leukocyte count, C-reactive protein level, creatinine level, lymphocyte count, leukocyte/lymphocyte ratio and the group of the pathogen that detected in the blood culture were retrospectively recorded., Results: Overall, 136 sepsis patients who were diagnosed with bacteraemia were included in the study. The PCT level was 7.31 ng mL -1 in the gram-negative group and 0.46 ng mL -1 in the gram-positive group. For PCT, the sensitivity was 70.83% and the specificity was 84.21%, with the cut-off value being ≤1.3. The area under the receiver operating characteristics curve for PCT was 0.80., Conclusion: Patients with gram-negative sepsis had higher PCT values than those with gram-positive sepsis. Our results suggest that PCT value may be a useful tool for distinguishing between gram-negative and gram-positive bacteraemia., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Background: Rapid, accurate, and reproducible assessment of intravascular volume status is crucial in order to predict the efficacy of volume expansion in septic patients. The aim of this study was to verify the feasibility and usefulness of the internal jugular vein collapsibility index (IJV-CI) as an adjunct to the inferior vena cava collapsibility index (IVC-CI) to predict fluid responsiveness in spontaneously-breathing patients with sepsis., Methods: Three stages of sonographic scanning were performed. Hemodynamic data were collected using the Ultrasonic Cardiac Output Monitor 1A system (Uscom, Ltd., Sydney, NSW, Australia) coupled with paired assessments of IVC-CI and IJV-CI at baseline, after passive leg raise (PLR), and again in semi-recumbent position. Fluid responsiveness was assessed according to changes in the cardiac index (CI) induced by PLR. Patients were retrospectively divided into 2 groups: fluid responder if an increase in CI (ΔCI) ≥15% was obtained after PLR maneuver, and non-responder if ΔCI was <15%., Results: Total of 132 paired scans of IJV and IVC were completed in 44 patients who presented with sepsis and who were not receiving mechanical ventilation (mean age: 54.6±16.1 years). Of these, 23 (52.2%) were considered to be responders. Responders had higher IJV-CI and IVC-CI before PLR maneuver than non-responders (p<0.001). IJV-CI of more than 36% before PLR maneuver had 78% sensitivity and 85% specificity to predict responder. Furthermore, less time was needed to measure venous diameters for IJV-CI (30 seconds) compared with IVC-CI (77.5 seconds; p<0.001)., Conclusion: IJV-CI is a precise, easily acquired, non-invasive parameter of fluid responsiveness in patients with sepsis who are not mechanically ventilated, and it appears to be a reasonable adjunct to IVC-CI.

Sepsis is one of the main causes of morbidity and mortality in critically ill patients despite the use of modern antibiotics and resuscitation therapies. Outcomes in sepsis have improved overall, probably because of an enhanced focus on early diagnosis and other improvements in supportive care, but mortality rates still remain unacceptably high. The diagnosis and definition of sepsis is a critical problem due to the heterogeneity of this disease process. Although it is apparent that much more needs to be done to advance our understanding, sepsis and related terms remain difficult to define. A 1991 consensus conference developed initial definitions that systemic inflammatory response syndrome (SIRS) to infection would be called sepsis. Definitions of sepsis and septic shock were revised in 2001 to incorporate the threshold values for organ damage. In early 2016, the new definitions of sepsis and septic shock have changed dramatically. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The consensus document describes organ dysfunction as an acute increase in total Sequential Organ Failure Assessment (SOFA) score two points consequently to the infection. A significant change in the new definitions is the elimination of any mention of SIRS. The Sepsis-3 Task Force also introduced a new bedside index, called the qSOFA, to identify outside of critical care units patients with suspected infection who are likely to develop sepsis. Recently updated the consensus definitions improved specificity compared with the previous descriptions., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Background: The aim of the present study was to determine the diagnostic and prognostic values of suPAR and to compare them to CRP and PCT in pediatric patients with systemic inflammatory response syndrome (SIRS)., Material-Methods: A prospective case-control study was performed.The study was performed in a tertiary university hospital which has a 649-bed capacity. Patients included 27 children with SIRS and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4-7th days of the hospital stay., Results: The median (min-max) serum levels of suPAR obtained on the first day of the admission were 10.06 (2.7-57.46) and 2.22 (1.08-5.13) ng/Ml for the SIRS group and control group, respectively. The median serum levels of suPAR in the SIRS group was significantly higher than that in the control group (p < 0.05). The serum suPAR levels was significantly higher in nonsurvivors than in survivors in SIRS group (p < 0.05). In the SIRS group, the area under the receiver operating characteristics curve (AUC ROC ) for suPAR revealed an optimum cut-off value, sensitivity, specificity, NPV and PPV of 0.978, 3.8 ng/mL, 96%, 96%, 96%, and 96%, respectively., Conclusions: We conclude that suPAR does have diagnostic value in children with SIRS. Additionally, persistent high serum suPAR level predicts mortality in SIRS in children., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Vitamin D plays a role in host defense and is known to be associated with mortality in patients in the intensive care unit (ICU). We aimed to evaluate the relationships between vitamin D levels and predictors of mortality in patients with ventilator-associated pneumonia (VAP) caused by extensively drug-resistant Acinetobacter baumanii (XDR A. baumanii)., Methodology: A retrospective single-center study was conducted in an 18-bed adult ICU of a teaching hospital, including all patients with VAP due to XDR A. baumanii. Levels of 25(OH)D, procalcitonin (PCT), C-reactive protein (CRP), n-terminal pro-BNP (NT-proBNP), as well as clinical scores (Sequential Organ Failure Assessment [SOFA], Acute Physiology And Chronic Health Evaluation [APACHE II], Clinical Pulmonary Infection Score [CPIS) were recorded., Results: Forty-for patients were studied over six months. All patients had vitamin D deficiency. The 28-day mortality in patients with 25(OH)D levels ≤ 10 ng/mL was higher than in patients with 25(OH)D > 10ng/mL (p = 0.001). The fourth- and seventh-day SOFA scores (p= 0.04 and p= 0.001) and first- and fourth-day procalcitonin levels (p = 0.03 and p = 0.004) were higher in patients with 25(OH)D levels ≤ 10 ng/mL. The clinical scores (SOFA, CPIS, and CEPPIS) and biomarkers (NT-proBNP, PCT) were negatively correlated with 25(OH)D levels in all study groups., Conclusions: Severe vitamin D deficiency was associated with adverse outcome in VAP due to XDR A. baumanii. Vitamin D levels may be a prognostic predictor of VAP. It is also important to evaluate the effect of rapid vitamin D replacement on mortality.

The aim of the present study was to determine the diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) in pediatric patients with febrile neutropenia. A prospective case-control study was performed. Patients included 29 children with febrile neutropenia (FN) and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4th to 7th days of the hospital stay. The median (minimum-maximum) serum levels of suPAR obtained on the first day of the admission were 2.08 (0.93-9.42) and 2.22 (1.08-5.13) ng/mL for the FN group and the control group, respectively. The median serum levels of suPAR in the FN and control groups were not significantly different (P = .053). The mean serum suPAR level was significantly higher in nonsurvivors than in survivors in the FN group (P < .05). In the FN group, the area under the receiver operating characteristics curve (AUCROC) for suPAR was 0.546, but no optimum cutoff value, sensitivity, specificity, negative predictive value (NPV), or positive predictive value (PPV) was obtained. We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children.

Primary graft dysfunction (PGD) is a severe form of acute lung injury that is a major cause of early morbidity and mortality encountered after lung transplantation. PGD is diagnosed by pulmonary oedema with diffuse alveolar damage that manifests clinically as progressive hypoxemia with radiographic pulmonary infiltrates. Inflammatory and immunological response caused by ischaemia and reperfusion is important with regard to pathophysiology. PGD affects short- and long-term outcomes, the donor organ is the leading factor affecting these adverse ramifications. To minimize the risk of PGD, reduction of lung ischaemia time, reperfusion optimisation, prostaglandin level regulation, haemodynamic control, hormone replacement therapy, ventilator management are carried out; for research regarding donor lung preparation strategies, certain procedures are recommended. In this review, recent updates in epidemiology, pathophysiology, molecular and genetic biomarkers and technical developments affecting PGD are described.

Objectives: The aim of this study was to evaluate the relationship between transesophageal ultrasonography-derived renal resistive index values (RRITEE) and a standard translumbar renal ultrasound-derived RRI (RRITLUSG). The effectiveness of each method to predict acute kidney injury (AKI) after cardiac surgery also was compared., Design: A prospective observational study., Setting: A teaching university hospital., Participants: Sixty patients undergoing cardiac surgery., Interventions: First, RRI was measured with both methods after anesthesia induction. Second, another measurement was performed with TEE after cardiopulmonary bypass and immediately following the surgery with translumbar ultrasound. To test the correlation between the 2 methods and to plot a Bland-Altman graph, preoperative RRI values measured by both techniques were used. Receiver operating characteristic curves also were plotted to compare the diagnostic values of RRI measured intraoperatively by TEE after cardiopulmonary bypass and by RRITLUSG after surgery., Measurements and Main Results: There was a statistically significant correlation between the 2 RRI measurement approaches (r = 0.86, p<0.0001). The Bland-Altman plot indicated good agreement between the methods. The area under the curve (AUC) of RRITEE in predicting AKI was 0.82 (95% confidence interval [CI] = 0.64-0.9, p = 0.001), and the AUC of RRITLUSG after surgery was 0.85 (95% CI = 0.7-0.98, p<0.0001). In predicting AKI, an uncertainty zone for RRITEE values between 0.68 and 0.71 was computed by the gray-zone approach., Conclusions: RRITEE showed clinically acceptable agreement with RRITLUSG. Indeed, RRI measured intraoperatively with TEE was comparable to RRITLUSG in terms of detecting postoperative AKI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Excessive fluid administration during lung resections is a risk for pulmonary injury. We analyzed the effect of intraoperative fluids on postoperative pulmonary complications (PCs)., Methods: Patients who underwent anatomic pulmonary resections during 2012 to 2013 were included. Age, weight, pulmonary function data, smoking (pack-years), the infusion rate and the total amount of intraoperative fluids (including crystalloid, colloid, and blood products), duration of anesthesia, hospital stay, PCs, and mortality were recorded. PCs were defined as acute respiratory distress syndrome, need for intubation, bronchoscopy, atelectasis, pneumonia, prolonged air leak, and failure to expand. Univariate analyses and multivariate logistic regression were performed. A Lowess curve was drawn for intraoperative fluid threshold., Results: In 139 patients, types of resections were segmentectomy-lobectomy (n = 69; extended n = 37; video-assisted thoracoscopic surgery n = 19) and pneumonectomy (n = 9; extended n = 5). One hundred sixty-one PCs were observed in 76 patients (acute respiratory distress syndrome [n = 5], need for intubation [n = 9], atelectasis [n = 60], need for bronchoscopy [n = 19], pneumonia [n = 26], prolonged air leak [n = 19], and failure to expand [n = 23]). Overall mortality was 4.3% (6 out of 139 patients). Mean hospital stay was 8.5 ± 4.8 days. Univariate analyses showed that smoking, intraoperative total amount of fluids, crystalloids, blood products, and infusion rate as well as total amount of crystalloids and infusion rate during the postoperative first 48 hours were significant for PCs (P = .033, P < .0001, P = .001, P = .03, P < .0001, P = .002, and P < .0001, respectively). In multivariate logistic regression analysis intraoperative infusion rate (P < .0001) and smoking were significant (P = .023). An infusion rate of 6 mL/kg/h was found to be the threshold., Conclusions: The occurrence of postoperative PCs is seen more frequently if the intraoperative infusion rate of fluids exceeds 6 mL/kg/h., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

Preservation of cardiac output (CO) and pulmonary artery pressure (PAP) is vital to maintaining tissue oxygenation in sepsis. This feasibility study tested the hypothesis that therapeutic intra-thoracic pressure regulation (tIPR), delivered with a novel device, was designed to non-invasively enhance venous return by creating sub-atmospheric intra-thoracic pressure during the expiratory phase of mechanical ventilation, improves CO without fluid resuscitation in a porcine E. coli peritonitis model of sepsis. Seven pigs were intubated, anaesthetized and instrumented with a Swan-Ganz and femoral artery catheter. After a 30 min basal period, a fibrin clot containing 4-5 × 10(9) cfu kg(-1) E. coli O111.B4 was implanted in the peritoneum. One hour after clot implantation, tIPR was utilized for 30 min and then removed from the ventilator circuit for 30 min. This tIPR cycle was repeated 4-times. Changes in haemodynamic parameters were calculated by comparing pre-tIPR values to peak values during tIPR administration. Following peritonitis, tIPR significantly increased the peak cardiac index (mean ± SEM) (14.8 ± 2.6 vs 7.9 ± 2.3 ml kg(-1)) and mean arterial pressure (10.2 ± 1.5 vs 4.9 ± 1.1 mmHg) and simultaneously decreased PAP (-7.7 ± 1.5 vs -2.7 ± 0.8 mmHg). These results support the feasibility of the concept that therapeutic application of negative expiratory pressure may provide a non-invasive and complementary approach to increase cardiac output and organ perfusion in the setting of septic shock.

Indirect acute lung injury is associated with high morbidity and mortality. We investigated the link between Rho kinase (ROCK) activation and apoptotic cell death in sepsis induced acute lung injury. This hypothesis was tested by administering a specific, selective inhibitor of ROCK (Y-27632) to rats subjected to cecal ligation and puncture (CLP). Rats were randomly divided into 4 groups as; sham-operated, sham + Y-27632, CLP and CLP + Y-27632. Twenty-four hours later, each experiment was terminated and lungs analyzed. Histopathology was assessed by hematoxylin-eosin staining and the presence of apoptosis was evaluated through the TUNEL assay. Pulmonary activity of caspase 3 and ROCK 1 & 2 were measured by western blot. Interstitial edema, severely damaged pulmonary architecture with massive infiltration of the inflammatory cells and an increase in lung tissue TBARS levels as well as 3-NT to total tyrosine ratios were observed in untreated CLP animals. Pretreatment of animals with Y-27632, reduced lung injury in the CLP induced septic rats in each of these parameters of lung injury (p<0.05). Western immunoblot revealed active caspase cleavage and increased expression of active fragment of ROCK 1 & 2 in the CLP group. TUNEL assay showed an increase in percentage of apoptotic cells when comparing the CLP group with the CLP + Y-27632 group. These results suggest an important role of Rho kinase in sepsis induced lung injury by a mechanism that might be related to oxidative and/or nitrosative stress mediated caspase cleavage leading to apoptosis.

Background: Clinical and experimental studies have shown that the laparoscopic procedure provides a typical model of ischemia-reperfusion injury in the organs by oxygen-derived free radicals. A pneumoperitoneum produces ischemia during insufflation and reperfusion during desufflation. The aim of this study was to assess the causative role of free radical-mediated reactions in tissue damage under different intra-abdominal insufflation pressures., Materials and Methods: Thirty five mature New Zealand white rabbits were assigned to three groups of 10 animals. In groups 1, 2, and 3, the designated pressures of 10, 15, and 20 mm Hg, respectively. The remaining 5 animals underwent laparotomy, using a 10-cm midline incision taken as group 4 (control). Blood samples were collected before (0 minutes) and at the end of the procedure (60 minutes). After the collection of the last blood samples, all animals were sacrificed and the samples from the liver, kidney, and gut were obtained for histologic evaluation and also measurements of tissue malondialdehyde (MDA) levels., Results: The nitric oxide levels were not changed in groups 1 and 2, but increased significantly in group 3. Tissue MDA levels were significantly higher in groups 1 and 2 than groups 3 and 4. Histopathologic examination of the kidney revealed some findings of reversible hypoxic cell injury, including acute cellular swelling, vascular congestion, and some early findings of irreversible injury, such as lysis of the cytoplasmic membrane in all groups and focal parancymal bleeding area in only group 3 as a consequence of increased pressure. Liver histology revealed cellular swelling and karyorhexis in hepatocytes in group 1, whereas only congestion and sinusoidal dilatation was observed in groups 2 and 3., Conclusion: Our experimental study showed that abdominal insufflation causes ischemia and free radical production, which seems responsible for the cell damage that occured during laparoscopic surgery.

Background: It is generally accepted that proinflammatory mediators, including cytokines, are responsible for the metabolic changes associated with injury. Recent clinical and experimental studies have also shown that the laparoscopic procedures actually produce ischemia-reperfusion injury in the organs by oxygen-derived free radicals. This study aimed to assess the effect of different insufflation pressures and laparotomy on tissue response by comparing the proinflammatory cytokines, C-reactive protein, and serum and tissue levels of oxygen-derived free radicals., Methods: Forty mature New Zealand white rabbits were assigned to 4 groups of 10 animals. In groups 1 to 3, CO2 pneumoperitoneum was created using an automatic insufflator to the designated pressure of 10, 15, and 20 mm Hg, respectively. The remaining 10 animals underwent laparotomy using 10 cm midline incision (group 4). Blood samples were collected before (0 min) and at the end of the procedure (60 min). After the collection of last blood samples, all animals were killed and samples from liver and gut were obtained for measurements of tissue malondialdehyde levels and histology., Results: The proinflammatory cytokine levels were increased significantly in groups 1 to 3, but did not change in the laparotomy group. Serum C-reactive protein levels were elevated in all groups. The comparison of the results between the laparotomy and laparoscopy groups showed that serum interleukin 6 and nitric oxide levels were significantly elevated in relation the intra-abdominal pressure, and serum interleukin 6 and nitric oxide levels peaked in group 3. Tissue malondialdehyde levels were significantly higher in groups 1 and 2 than in groups 3 and 4., Conclusions: The findings of our experiment suggest that the elevated intra-abdominal pressure is responsible for ischemia, free radical production, and proinflammatory cytokine response-mediated cell damage during laparoscopic surgery.

Background: Remarkable progress has been made during the last decade in defining the molecular mechanisms that underlie septic shock. This rapidly expanding field is leading to new therapeutic opportunities in the management of severe sepsis., Aim: To provide the clinician with a timely summary of the molecular biology of sepsis and to better understand recent advances in sepsis research., Data Selection: Medline search of relevant publications in basic mechanisms of sepsis/severe sepsis/septic shock, and selected literature review of other manuscripts about the signalosome, inflammasome, apoptosis, or mechanisms of shock. DATA SYNTHESIS AND FINDINGS: The identification of the toll-like receptors and the associated concept of innate immunity based upon pathogen- or damage-associated molecular pattern molecules allowed significant advances in our understanding of the pathophysiology of sepsis. The essential elements of the inflammasome and signal transduction networks responsible for activation of the host response have now been characterized. Apoptosis, mitochondrial dysfunction, sepsis-related immunosuppression, late mediators of systemic inflammation, control mechanisms for coagulation, and reprogramming of immune response genes all have critical roles in the development of sepsis., Conclusions: Many of these basic discoveries have direct implications for the clinical management of sepsis. The translation of these "bench-to-bedside" findings into new therapeutic strategies is already underway. This brief review provides the clinician with a primer into the basic mechanisms responsible for the molecular biology of sepsis, severe sepsis, and septic shock.

Nitric oxide (NO) is a unique and nearly ubiquitous molecule that is widely utilized as a signaling molecule in cells throughout the body. NO is highly diffusible, labile, and multiply reactive, suiting it well for its role as an important regulator of a number of diverse biologic processes, including vascular tone and permeability, platelet adhesion, neurotransmission, and mitochondrial respiration. NO can protect cells against antioxidant injury, can inhibit leukocyte adhesion, and can participate in antimicrobial defense, but can also have deleterious effects, including inhibition of enzyme function, promotion of DNA damage, and activation of inflammatory processes. This molecule's chemistry dictates its biologic activity, which can be both direct and indirect. In addition, NO has bimodal effects in a number of cells, maintaining homeostasis at low doses, and participating in pathophysiology in others. Perturbation of NO regulation is involved in the most important and prevalent disease processes in critical care units, including sepsis, acute lung injury, and multiple organ failure. Given that NO is ubiquitous, highly diffusible, and promiscuously reactive, its regulation is complex. The NO concentration, kinetics, and localization, both inside and outside the cell, are clearly crucial factors. In the present update we review a selection of studies that have yielded important information on these complex but important issues. Interpretation of these and other studies aimed at elucidating physiologic and pathophysiologic roles of NO must take this complexity into account. A full review of the role of NO in these diseases is beyond the scope of the current manuscript; the present article will focus on recent advances in understanding the complex role of NO in health and disease.

Background: Vibration response imaging (VRI) is a computer-based technology that creates a visual dynamic two-dimensional image of distribution of vibration within the lung during the respiratory process. The acoustic signals, recorded from 36 posteriorly positioned surface skin sensors, are transferred to a hardware board where several stages of filtering are applied to select a specific frequency band. The filtered output signal frequencies are presented as a gray-scale coded dynamic image, consisting of a series of 0.17 s frames, and as a table featuring the percentage contribution of each lung to the total vibration signal., Methods: We describe the VRI technology in detail and examine images obtained from consecutive intensive care unit (ICU) patients with one diseased lung on chest radiograph. ICU patients with normal chest radiographs are presented as controls. Analysis of the image was performed by comparing the weighted pixel count analysis from both lungs. In this method, the pixels in the image were assigned values based on their grayscale color with the darker pixels assigned higher values., Results: In patients with normal chest radiographs, the right and left lungs developed similarly in dynamic VRI images, and the percent lung vibrations from both sides were comparable (53%+/-12% and 47%+/-12%, respectively). In ICU patients with asymmetric lung disease, however, the percent lung vibrations from the diseased and nondiseased lungs were 27%+/-23% and 73%+/-23%, respectively (P<0.001). In patients with asymmetric lung disease (one lung has moderate to severe disease and the other appears normal or close to normal as per chest radiograph), the diseased lung usually appeared in VRI as irregular, smaller, and lighter in color (reduced vibration signal) when compared to the nonaffected lung. The weighted pixel count from diseased and nondiseased lungs were 33%+/-21% and 67%+/-21%, respectively (P < 0.003)., Conclusion: The VRI technology may provide a radiation-free method for identifying and tracking of asymmetric lung parenchymal processes.

Microcirculatory dysfunction is a critical element of the pathogenesis of severe sepsis and septic shock. In this Bench-to-Bedside review, we present: 1) the central role of the microcirculation in the pathophysiology of sepsis; 2) new translational research techniques of in vivo video microscopy for assessment of microcirculatory flow in human subjects; 3) clinical investigations that reported associations between microcirculatory dysfunction and outcome in septic patients; 4) the potential role of novel agents to "rescue" the microcirculation in sepsis; 5) current challenges facing this emerging field of clinical investigation; and 6) a framework for the design of future clinical trials aimed to determine the impact of novel agents on microcirculatory flow and organ failure in patients with sepsis. We specifically focus this review on the central role and vital importance of the nitric oxide (NO) molecule in maintaining microcirculatory homeostasis and patency, especially when the microcirculation sustains an insult (as with sepsis). We also present the scientific rationale for clinical trials of exogenous NO administration to treat microcirculatory dysfunction and augment microcirculatory blood flow in early sepsis therapy.

Background: Intrathecal morphine has been used in hopes of providing long-lasting postoperative analgesia in patients after cardiac surgery. The aim of this study was to evaluate the effects of 7 micro/kg intrathecal morphine administration in coronary bypass surgery in the postoperative period., Methods: We conducted a prospective, randomized, blinded, and controlled study. Twenty-three patients, who underwent primary elective coronary bypass surgery, were randomly allocated to receive morphine 7 micro/kg intrathecally, before the induction of general anesthesia (Group M, n = 12) or no intrathecal injection (Group C, n = 11). Pain scores, determined by visual analogue scale (VAS), were recorded immediately after extubation upon admission to the intensive care unit (ICU), at the 2nd, 4th, 6th, and 18th hour after extubation. Pethidine was administered if the patient's VAS > or = 4 and consumption was recorded. Extubation time and ICU length of stay were also recorded., Results: VAS scores were lower in the Group M at each measured time than the control group (p = 0.016, 0.023, 0.004, 0.0001, and 0.001, respectively). According to the VAS scores, pethidine requirement was lower in the Group M than the control (p = 0.001). Extubation time (3.58 +/- 1.57 vs. 4.86 +/- 1.38 hours, p = 0.045) and ICU length of stay (16.25 +/- 2.70 vs. 19.30 +/- 2.45 hours, p = 0.014) were also significantly shorter in the Group M than the control group. No significant complications were seen in this group of patients., Conclusions: Intrathecal morphine provided effective analgesia, earlier tracheal extubation and less ICU length stay after on-pump coronary bypass surgery. The influence on ICU length of stay requires further evaluations.

Purpose: We describe the effect that inadvertent esophageal intubation has on the images and on the vibration distribution of vibration response imaging (VRI)., Clinical Features: Vibration response imaging (VRI) is a novel, non-invasive, computer-based technology that measures vibration energy of lung sounds during respiration and displays regional intensity, in both visual and graphic format. Vibration response images, obtained prior to tracheal intubation (spontaneous breathing) and during endotracheal ventilation using a controlled mode, resulted in evenly distributed vibrations throughout the patient's lungs. During inadvertent esophageal ventilation, however, the majority of vibrations were detected in the upper regions of the image, compared to those of the lower (60% vs 8%, respectively). During spontaneous breathing and endotracheal ventilation, the midclavicular column of sensors, located over the centre of each lung, detected more vibrations compared to either the medial or the axillary column of sensors. During inadvertent esophageal ventilation, more vibrations were detected by the medial column of sensors (nearest to the midline/esophagus); and fewer were detected by the sensors that were positioned more laterally., Conclusion: This report illustrates the potential for a visual image of distribution of lung vibration energy to differentiate endotracheal intubation from inadvertent esophageal intubation.

Introduction: We tested the feasibility of a new technique of direct left ventricular endocardial lead placement across the aortic valve in a chronic (six month) pig model. The potential for aortic valve damage, systemic embolization, and pacing lead maturation and function within the left ventricle are unknown., Methods: Ten minipigs were successfully implanted with a transaortic left ventricular lead (Medtronic CapSureFix, Minneapolis, MN, USA) placed in the left ventricular apex via the carotid artery. Each pig received either a polyurethane (n = 5) or silicone (n = 5) lead. Post implant each pig received clopidogrel and aspirin for seven days. After six months all surviving pigs underwent thorough necropsy., Results: Each pig had adequate sensing (12.1 +/- 4 mV) and pacing thresholds (0.79 +/- 0.2 @ 0.5 V) at implant. Postoperatively two pigs died of a respiratory illness. One pig died postoperatively due to sepsis. At the six-month follow-up, all surviving pigs (n = 7) were in a healthy state. Of the pigs without dislodgement (n = 5) there was adequate sensing, but a rise in pacing thresholds. Echocardiography revealed a normal ejection fraction and only trace to mild aortic insufficiency in all pigs. Of the seven surviving pigs there were no thromboembolic events noted. One silicone lead was noted to have thrombosis along the lead screw and shaft., Conclusion: Direct transaortic placement of a left ventricular lead is feasible. After six months, there was no significant aortic regurgitation and no evidence of thromboembolism despite no anticoagulation. Lead function was acceptable and only one silicone lead (and no polyurethane lead) was noted to have significant thrombosis.

Purpose of Review: The rationale for therapeutic targets in sepsis has arisen from the concept of pathogenesis. This review focuses on recent advances in pathogenesis of sepsis that can aid in management of sepsis patients., Recent Findings: Cellular survival in sepsis is related to the magnitude of the stimulus, the stage of the cell cycle and the type of microbe. While phenotypic modification of the endothelium (procoagulant and proadhesive properties, increased endothelial permeability, endothelial apoptosis and changes in vasomotor properties) leads to vasoplegia as a direct correlate to septic shock mortality, phenotypic changes in the epithelium cause activation of the virulence of the opportunistic pathogens and loss of mucosal barrier function, the latter causing a vicious circle in severe sepsis. Early identification of sepsis with protocolized screening, triggering evidence-based protocolized care, is anticipated to reduce sepsis morbidity and mortality. Current treatment of sepsis includes early antibiotic therapy, early aggressive goal-directed resuscitation targeting tissue hypoperfusion, steroids (for refractory shock), activated protein C (for high risk of death) and maintaining support of organ systems., Summary: A better understanding of pathogenesis of sepsis has led to specific proven management tools that are likely to improve clinical outcome once incorporated into protocolized care.

Objective: To investigate the effects of genistein on reperfusion injury in a rat ovarian torsion-detorsion model., Design: Controlled experimental study., Setting: University animal research laboratory., Subject(s): Thirty-two Wistar-Albino rats., Intervention(s): The rats were divided into four groups. Sham operation was performed in group I. In group II, 5 mg/kg genistein was given intraperitoneally (IP) during laparotomy, and right ovaries were removed 4 hours later. In group III, right ovaries were subjected to 4 hours of adnexal ischemia by use of vascular clips, and after ischemic insult, 4 hours of reperfusion was maintained by removing the clips. In group IV, after the ischemic period, 5 mg/kg genistein was given IP, and 4 hours of reperfusion was maintained. Right ovaries were surgically removed at the end of the procedure in each group., Main Outcome Measure(s): Ovarian histopathologic findings were scored and compared among study groups. Serum and ovarian tissue malondialdehyde (MDA), glutathione peroxidase, and superoxide dismutase, levels were measured., Result(s): Ovarian tissue damage scores were significantly different among groups and were seen to correlate with ovarian tissue MDA levels. Genistein significantly decreased the tissue damage scores, ovarian tissue MDA levels, and serum MDA levels., Conclusion(s): Genistein attenuates ischemia-reperfusion injury in rat adnexal torsion-detorsion model.

Introduction: There are several ventilator modes that are used for maintenance mechanical ventilation but no conclusive evidence that one mode of ventilation is better than another. Vibration response imaging is a novel bedside imaging technique that displays vibration energy of lung sounds generated during the respiratory cycle as a real-time structural and functional image of the respiration process. In this study, we objectively evaluated the differences in regional lung vibration during different modes of mechanical ventilation by means of this new technology., Methods: Vibration response imaging was performed on 38 patients on assist volume control, assist pressure control, and pressure support modes of mechanical ventilation with constant tidal volumes. Images and vibration intensities of three lung regions at maximal inspiration were analyzed., Results: There was a significant increase in overall geographical area (p < 0.001) and vibration intensity (p < 0.02) in pressure control and pressure support (greatest in pressure support), compared to volume control, when each patient served as his or her own control while targeting the same tidal volume in each mode. This increase in geographical area and vibration intensity occurred primarily in the lower lung regions. The relative percentage increases were 28.5% from volume control to pressure support and 18.8% from volume control to pressure control (p < 0.05). Concomitantly, the areas of the image in the middle lung regions decreased by 3.6% from volume control to pressure support and by 3.7% from volume control to pressure control (p < 0.05). In addition, analysis of regional vibration intensity showed a 35.5% relative percentage increase in the lower region with pressure support versus volume control (p < 0.05)., Conclusion: Pressure support and (to a lesser extent) pressure control modes cause a shift of vibration toward lower lung regions compared to volume control when tidal volumes are held constant. Better patient synchronization with the ventilator, greater downward movement of the diaphragm, and decelerating flow waveform are potential physiologic explanations for the redistribution of vibration energy to lower lung regions in pressure-targeted modes of mechanical ventilation.

Purpose of Review: The large variability in clinical practice plus the increasing awareness that certain processes of care are associated with improved medical outcomes has led to the development of clinical practice guidelines in serious infection. The evolution of guidelines and their impact on delivery of care in severe infection is reviewed., Recent Findings: Guidelines development has centered around community- and hospital-acquired pneumonia as well as sepsis. The Institute of Healthcare Improvement has emerged as an international leader in changing healthcare professional behavior to be consistent with clinical recommendations in infection-related morbidity. These educational programs are designed to increase awareness of guidelines recommendations and to optimize their implementation. Change bundles are selected sets of interventions or processes distilled from evidence-based practice guidelines that are likely to improve outcome. As new evidence is published, and as experts ponder how the guidelines should best be expressed in the bundles, the bundles will be adapted to optimize their utility., Summary: The change bundle approach to performance improvement (guidelines-based) is the key to change in practice. The Surviving Sepsis Campaign/Institute of Healthcare Improvement sepsis change bundles are an excellent example of progress along these lines.

The treatment of severe sepsis includes three essential principles: eradication of the inciting infection using source control measures and empiric antibiotics, hemodynamic resuscitation of hypoperfusion to avoid acute life-threatening organ dysfunction, and sustained support of organ system dysfunction using interventions that minimize organ injury. Therapy can be divided into immediate steps taken to stabilize the patient, followed by more definitive therapeutic intervention. The evidence for best clinical practice for resuscitation, management of infection, and intensive care unit supportive care has recently been synthesized by the Surviving Sepsis Campaign and published as evidence-based guidelines for the management of severe sepsis and septic shock.

The objective of this study was to investigate the effects of 3-aminobenzamide (3-AB) on tissue damage in lung after hind limb ischemia-reperfusion (I/R), by assessing blood biochemical assay and histopathological analysis. Thirty-five adult Wistar rats were divided into five groups. After application of anaesthesia both hind limbs were occluded with tourniquets. Following ischemia period for 60 min, the tourniquets were removed allowing reperfusion for 120 min. The IR group received 0.5 ml of saline while the IR+AB group received 3-AB (10 mgkg(-1) intraperitoneally). The IR+DMSO group was given 0.5 ml 10% DMSO 30 min before the removal of the tourniquets. The control group received 0.5 ml saline and the AB group received 0.5 ml 3-AB (10 mgkg(-1)) intraperitoneally. At the end of the reperfusion period, mid-line sternotomy was performed. Blood samples were taken with cardiac puncture. Bronchoalveolar lavage (BAL) of the left lung was performed with saline. Right lung was preserved for histopathological evaluation and biochemical examination. Lung tissue malondialdehyde (MDA) and 3-nitrotyrosine levels, myeloperoxidase and Na+/K+ ATP-ase activities, wet to dry weight ratios, and plasma and BAL fluid MDA levels were determined. Histopathological evaluation was performed, too. Hind limb IR caused significant increase in the lung tissue 3-NT to total tyrosine ratio (p = 0.014), wet to dry weight ratio (p = 0.000), MPO activity (p = 0.000), and MDA levels (p = 0.000). The animals treated with 3-AB showed a statistically significant decrease in these values (p < 0.05). Na+/K+ ATP-ase activity which was found to be decreased significantly with IR, returned to near normal levels with 3-AB treatment. Additionally, lung tissue injury in IR group characterized with moderate interstitial congestion and neutrophil infiltration, showed remarkable amelioration following 3-AB treatment. Our results strongly support the view that poly(ADP-ribose) polymerase (PARP) plays an important role in the inflammatory process in hind limb I/R-induced lung injury and as a PARP inhibitor, 3-AB seems to have a potential to treat this inflammatory injury.

This study was designed to investigate the effect of selenium on ipsilateral and contralateral testicular damage after unilateral testicular torsion/detorsion (T/D). Thirty-two male rats were divided into four groups, each containing eight rats. Torsion was created by rotating the right testis 720 degrees in a clockwise direction. Group 1 underwent sham operation to determine basal values for biochemical and histopathological evaluation. Sham operation was performed in group 2, and sodium selenate (0.2 mg/kg) was given intraperitoneally. Group 3 served as a T/D group, receiving 4-h torsion and 4-h detorsion. Similarly, in group 4 sodium selenate (0.2 mg/kg) was injected intraperitoneally 20 min before detorsion. Bilateral orchiectomies were performed for measurement of tissue malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities and histopathologic examination. The results were compared statistically. The highest MDA and the lowest SOD values were determined in both testes in group 3. There were statistically significant differences in MDA levels and SOD activities in group 3 compared with group 4. Specimens from group 3 had a significantly greater histologic injury than other groups. These results suggest that ischemia-reperfusion injury occurred in both testes after unilateral testicular T/D and that selenium administration before detorsion prevents reperfusion injury in testicular torsion.