Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients.

BACKGROUND AND OBJECTIVES: An effective treatment option is not yet available for SARS-CoV2, which causes the COVID-19 pandemic and whose effects are felt more and more every day. Ivermectin is among the drugs whose effectiveness in treatment has been investigated. In this study; it was aimed to investigate the presence of gene mutations that alter ivermectin metabolism and cause toxic effects in patients with severe COVID-19 pneumonia, and to evaluate the effectiveness and safety of ivermectin use in the treatment of patients without mutation. MATERIALS AND METHODS: Patients with severe COVID19 pneumonia were included in the study, which was planned as a prospective, randomized, controlled, single-blind phase 3 study. Two groups, the study group and the control group, took part in the study. Ivermectin 200 mcg/kg/day for 5 days in the form of a solution prepared for enteral use added to the reference treatment protocol -hydroxychloroquine + favipiravir + azithromycin- of patients included in the study group. Patients in the control group were given only reference treatment with 3 other drugs without ivermectin. The presence of mutations was investigated by performing sequence analysis in the mdr1/abcab1 gene with the Sanger method in patients included in the study group according to randomization. Patients with mutations were excluded from the study and ivermectin treatment was not continued. Patients were followed for 5 days after treatment. At the end of the treatment and follow-up period, clinical response and changes in laboratory parameters were evaluated. RESULTS: A total of 66 patients, 36 in the study group and 30 in the control group were included in the study. Mutations affecting ivermectin metabolism was detected in genetic tests of six (16.7%) patients in the study group and they were excluded from the study. At the end of the 5-day follow-up period, the rate of clinical improvement was 73.3% (22/30) in the study group and was 53.3% (16/30) in the control group (p = 0.10). At the end of the study, mortality developed in 6 patients (20%) in the study group and in 9 (30%) patients in the control group (p = 0.37). At the end of the follow-up period, the average peripheral capillary oxygen saturation (SpO2) values of the study and control groups were found to be 93.5 and 93.0%, respectively. Partial pressure of oxygen (PaO2)/FiO2 ratios were determined as 236.3 ± 85.7 and 220.8 ± 127.3 in the study and control groups, respectively. While the blood lymphocyte count was higher in the study group compared to the control group (1698 ± 1438 and 1256 ± 710, respectively) at the end of the follow-up period (p = 0.24); reduction in serum C-reactive protein (CRP), ferritin and D-dimer levels was more pronounced in the study group (p = 0.02, p = 0.005 and p = 0.03, respectively). CONCLUSIONS: According to the findings obtained, ivermectin can provide an increase in clinical recovery, improvement in prognostic laboratory parameters and a decrease in mortality rates even when used in patients with severe COVID-19. Consequently, ivermectin should be considered as an alternative drug that can be used in the treatment of COVID-19 disease or as an additional option to existing protocols.

Does ultrasonographic assessment of gastric antrum correlate with gastric residual volume in critically ill patients? A prospective observational study.

This study aimed to evaluate the relationship between ultrasonographic gastric antral measurements and aspirated gastric residual volume (GRV) in mechanically ventilated critically ill patients receiving enteral nutrition (EN). This prospective observational study included 56 enterally-fed critically ill patients in one-year period. All imaging procedures were done at 30-degree head-of-bed elevation and supine position on epigastric region of abdomen with 2.5-6 MHz convex-array probe just before routine GRV aspiration. The antral cross-sectional area (CSA) was calculated by measuring the anteroposterior (dAP) and craniocaudal diameters (dCC) of the gastric antrum. Total 283 ultrasonographic gastric antrum imaging procedures were done. In only eight (2.82%) attempts, the antrum could not be visualized due to inhibition from intra-gastric air or gas in the surrounding intestinal lumen. The calculated mean antral CSA was 568.15 ± 348.37 mm2 (103.43-2,846.30). The antral CSA correlated significantly with aspirated GRV, and the antral CSA increased linearly with increasing aspirated GRV (R2 = 0.73, p < 0.0001). In Receiver operating characteristic (ROC) analysis of antral CSA ≥ 920 mm2 (mean + 1*SD) for estimating aspirated GRV, the area under the curve (AUC) was 0.848 (95% CI, 0.76 ~ 0.93) (p < 0.0001), and ROC analysis of antral CSA to discriminate aspirated GRV ≥ 250 mL showed a significant relation (AUC = 0.969, 95% CI 0.94 ~ 0.99, p < 0.0001). Ultrasonographic measurement of gastric antral CSA is an easy and reliable bedside procedure to estimate GRV in critically ill patients receiving EN in 30-degree head-of-bed elevation and supine position. Trial registration number: NCT04413474, date of registration: June 17, 2020, retrospectively registered.

The timing of intubation and principles of ICU care in COVID-19

Coronavirus disease-19 (COVID-19) has been a serious health problem since it was first identified in Wuhan, China, in December 2019 and has created a global crisis with its economic, sociological, and psychological aspects. Approximately 15% of cases have a severe clinical presentation, and 5% of patients require admission to the intensive care unit. A significant proportion of patients presents with a rapidly progressing acute respiratory failure and require invasive mechanical ventilation. This article aimed to evaluate how the optimal intubation timing should be determined in cases of acute respiratory failure due to COVID-19 and to offer recommendations for basic intensive care support in the light of our current knowledge.

Serum neuron-specific enolase and S-100ß levels as prognostic follow-up markers for oxygen administered carbon monoxide intoxication cases.

Serum neuron-specific enolase (NSE) and S-100ß levels are considered novel biochemical markers of neuronal cell injury. In this study, the initial and post-treatment levels of NSE and S-100ß were compared in carbon monoxide (CO) poisoning patients, who received normorbaric oxygen (NBO) or hyperbaric oxygen (HBO) therapy. Forty consecutive patients with acute CO poisoning were enrolled in this prospective, observational study. According to their clinical symptoms and observations, twenty patients were treated with NBO, and the other twenty with HBO. Serum S-100ß and NSE levels were measured both at time of admission and 6 h later (post-treatment). Serum NSE and S-100ß values decreased significantly in both of the therapeutic modalities. The initial and post-treatment values of NSE and S-100ß in NBO or HBO patients were comparable. A clear negative correlation was observed between the decrease of NSE and S-100ß levels and initial blood carboxyhemoglobin levels. In conclusion, the present results suggested the use of serum S-100ß and NSE levels as indicators for brain injury. Due to the significant increase of their values with oxygen therapy, they may also be useful as prognostic follow-up markers. However, the current findings reflected no difference between the efficacy of NBO or HBO therapy.

Efficacy of high-flow oxygen therapy in all types of headache: a prospective, randomized, placebo-controlled trial.

OBJECTIVE: We aimed to assess the efficacy of oxygen inhalation therapy in emergency department (ED) patients presenting with all types of headache. METHOD: We performed a prospective, randomized, double-blinded, placebo-controlled trial of patients presenting to the ED with a chief complaint of headache. The patients were randomized to receive either 100% oxygen via nonrebreather mask at 15 L/min or the placebo treatment of room air via nonrebreather mask for 15 minutes in total. We recorded pain scores at 0, 15, 30, and 60 minutes using the visual analog scale. At 30 minutes, the patients were assessed for the need for analgesic medication. Patient headache type was classified by the treating emergency physician using standardized diagnostic criteria. RESULTS: A total of 204 patients agreed to participate in the study and were randomized to the oxygen (102 patients) and placebo (102 patients) groups. Patient headache types included tension (47%), migraine (27%), undifferentiated (25%), and cluster (1%). Patients who received oxygen therapy reported significant improvement in visual analog scale scores at all points when compared with placebo: 22 mm vs 11 mm at 15 minutes (P < .001), 29 mm vs 13 mm at 30 minutes (P < .001), and 55 mm vs 45 mm at 60 minutes (P < .001). When questioned at 30 minutes, 72% of patients in the oxygen group and 86% of patients in the placebo group requested analgesic medication (P = .005). CONCLUSION: In addition to its role in the treatment of cluster headache, high-flow oxygen therapy may provide an effective treatment of all types of headaches in the ED setting.

Hyperbaric oxygen therapy alleviates oxidative stress and tissue injury in renal ischemia/reperfusion injury in rats.

Hyperbaric oxygen (HBO) therapy has been shown to attenuate renal ischemia/reperfusion (I/R) injury in rats, when applied in the early reperfusion period. The aim of this study was to elucidate possible beneficial effects of HBO therapy on renal I/R injury, when applied 24 h after ischemia. Rats were randomized into three groups: (1) control group (n = 20), (2) I/R group (n = 20), and (3) I/R + HBO group (n = 20). Renal I/R injury was created by interrupting renal blood flow for 30 min with a non-traumatic vascular clamp. HBO therapy was administered 24 h after I/R injury and continued for 5 days. At the end of the study, rats were sacrificed under anesthesia, blood was drawn, and right kidneys were harvested for analysis. Renal I/R injury increased serum and tissue malondialdehyde (MDA) levels and reduced superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. HBO therapy attenuated MDA levels by increasing SOD and GPx activities. HBO therapy also prevented neutrophil infiltration and tissue injury in kidneys. Taken together, HBO therapy has been found to be effective in the delayed period of I/R injury.

Ozone therapy and hyperbaric oxygen treatment in lung injury in septic rats.

Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO) therapy. It has been shown that ozone therapy (OT) reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1ß and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1ß, lung GSH-Px and histologic outcome.

Ischemia-modified albumin levels in carbon monoxide poisoning.

OBJECTIVES: Ischemia-modified albumin (IMA) is an emerging diagnostic biomarker for many ischemic conditions. This study was conducted to investigate whether there is a change in IMA levels in carbon monoxide (CO) poisoning and, if so, the clinical relevance of IMA levels. METHODS: This cohort study, performed between November 2008 and April 2009, compared the serum IMA levels of 33 CO-poisoned patients taken at the time of presentation at the emergency department and after 3 hours of treatment and 49 healthy controls. In addition, IMA and carboxyhemoglobin levels were analyzed according to CO poisoning patients' poisoning severity scores. RESULTS: Carbon monoxide patients' IMA levels were higher than those of the control group both at time of admission and at the third hour of the treatment, P < .0001. A significant fall was determined in carboxyhemoglobin (CO-Hb) levels at the end of the third hour of treatment, P < .0001. However, there was no significant difference between the IMA levels measured at admission and at the end of the third hour of treatment (P > .05). There was no significant correlation between IMA and CO-Hb levels in CO-poisoned patients. Also, there was no difference in blood IMA levels in classification according to patients' poisoning severity score and CO-Hb levels. CONCLUSION: Results from this pioneering study established a high level of IMA in CO-poisoned patients, suggesting that IMA may also be sensitive to hypoxia. Considering the preliminary nature of this study, the clinical utility of IMA levels in CO poisoning should be further investigated with more comprehensive studies.

Neurological manifestations of COVID-19 in confirmed and probable cases: A descriptive study from a large tertiary care center.

During the early phase of the COVID-19 pandemic, it was thought that virus affects only the respiratory system. However, now it is clear that it can affect other systems too, particularly the nervous system. We aimed to identify the most common neurological symptoms and findings of COVID-19 in hospitalized patients and investigate the relationship between these symptoms and clinical, radiological, and laboratory findings. A total of 307 patients, including 125 women and 182 men, were included in the study. They were classified as "confirmed cases" or "probable cases" based on confirmatory tests, including polymerase chain reaction testing of a nasopharyngeal sample or validated antibody test. All medical records, including medical history, clinical course, laboratory data, and radiographic studies, were evaluated by two expert neurologists. Altered mental status (AMS) is the most common neurological finding in both confirmed (68.1%) and probable cases (71.8%). Pre-existing neurological diseases were detected as an independent risk factor for AMS. The mortality rate of patients with AMS was dramatically higher than normal mental status in both confirmed (43.9% vs. 6.2%) and probable cases (47.3% vs. 6.9%) (for both p:0.001). The frequency of seizure attacks was 13.2% in confirmed and 17.5% in probable cases (p:0.321). The mortality rate was higher in patients with a seizure attack in both groups. We conclude that AMS was one of the most common neurological manifestations in this cohort of COVID-19 patients. The development of mental deterioration increases mortality dramatically. Also, the existence of seizure attacks was associated with a high mortality rate.

Effects of long term hydrophilic bile acid therapy on in vitro contraction of gallbladder muscle strips in patients with cholesterol gallstones.

AIM: To evaluate ursodeoxycholic acid (UDCA) therapy on the in vitro contraction of gallbladder smooth muscle strips from cholesterol gallstone patients. METHODS: The contraction forces of gallbladder smooth muscle strips from 28 patients with cholesterol gallstones treated with UDCA were compared with contraction forces from 14 untreated patients. The strips were stimulated with increasing concentrations of cholecystokinin-8 (CCK-8). RESULTS: Although the contraction forces that developed in response to CCK-8 were higher in strips from specimens of UDCA treated patients compared to untreated patients, longer treatment periods (6-wk) caused more contraction responses than the short treatment period of 3-wk (F = 19.297, 1.85 +/- 0.22 g vs 1.70 +/- 0.10 g, P < 0.01). Contraction forces developed with maximal stimulation with KCl in the 6-wk treatment group were also higher than contraction forces in the untreated group (F = 4.274, 3.77 +/- 0.45 g vs 3.30 +/- 0.30 g, P < 0.05). CONCLUSION: Six-week UDCA treatment caused an increase in contractions of muscle strips from patients with cholesterol gallstones when compared to shorter treatment administration or controls. We suggest that extending UDCA treatment periods may cause more effective contractions in the gallbladder, and thereby increase the rate of response to treatment.

Functions and oxidative stress status of leukocytes in patients with nephrotic syndrome.

This study was conducted to establish the functions and oxidative stress status in leukocytes of adult patients with nephrotic syndrome. Thirty adult patients with nephrotic syndrome and 32 controls were included. Phagocytosis ability, the killing ability of the micro-organism phagosited of polymorphonuclear leukocytes (PMNL) and monocytes, along with oxidative stress parameters of PMNLs were assessed. There was no statistically significant difference in phagocytosis function of PMNLs and monocytes of patients when compared to those of controls. PMNL burst activities of the patient and control groups also showed no difference; however, the monocyte burst activities of patients were significant (p = 0.012). The glutathione peroxidase (GSH-Px) activities in PMNLs of the patients with nephrotic syndrome were significantly higher (p = 0.026) when compared to those of controls. In comparison with those of the control subjects, the patients had also higher selenium levels in their PMNLs (p < 0.001). Although PMNL malonyldialdehyde (MDA) levels of the patients seem to be higher than those of controls, the difference had no statistical significance (p = 0.071). Conclusively, in the patients with nephrotic syndrome, PMNLs appear to be exposed to an oxidative stress as indicated by their increased GSH-Px activities and selenium content. However, PMNLs in nephrotic syndrome patients seem to be coping with the insulting oxidative stress, as suggested by their near-normal MDA productions. Furthermore, these data suggest that nephrotic syndrome appears not to have an influence on phagocytosis and killing abilities of granulocytes and monocytes as long as these cells can overcome the oxidative stress to which they are exposed in this disease.

The role of allopurinol in experimental acute necrotizing pancreatitis.

BACKGROUND & OBJECTIVES: Acute pancreatitis (AP) in its severe form can lead to severe complications and death. Translocation of bacteria from the gut is one of the most important factors in the development of septic complications and mortality in acute pancreatitis. Oxygen-derived free radicals have been suggested to play a major role in the pathogenesis of AP. Xanthine oxidase enzyme is an important source of reactive oxygen metabolites. We undertook this study to evaluate the effect of allopurinol on bacterial translocation, oxidative stress and the course of AP in a rat model. METHODS: Male Sprague-Dawley rats (n=48) were randomly allocated into three equal groups. Acute pancreatitis (AP) was induced in group II (AP+Saline), and group III (AP+allopurinol) by retrograde infusion of taurocholate into the common biliopancreatic duct. Group I rats (Sham) received normal saline infusion into the common biliopancreatic duct for mimicking pressure effect. Group III rats were treated with allopurinol intraperitoneally for 48 h after induction of pancreatitis. Blood samples were drawn from all animals for biochemical analyses and pancreatic tissues were examined for bacterial translocation. RESULTS: Acute pancreatitis was developed in all groups, but not in group I (Sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Pathologic score of the pancreatitis in the allopurinol group (14.0 +/- 0.5) was lower when compared with group II (19.2 +/- 0.6) (P<0.001). Bacterial translocation to pancreas in group treated with allopurinol was significantly lower when compared with control group (p<0.02). Plasma glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels were higher and malondialdehyde (MDA) levels were lower in allopurinol group when compared with those in control groups. INTERPRETATION & CONCLUSION: Our findings suggested that addition of allopurinol to the treatment protocol in the acute pancreatitis might improve the pathologic score, bacterial translocation and oxidative stress parameters. However, more studies need to be done to confirm these findings.

[Sexual activity in cardiac patients]. / Kalp hastaliklarinda cinsel aktivite.

The question "extents of sexual activity", especially for a cardiac patient, seems enigmatic for patient himself and his physician. Cardiac patient's prejudice is that limitation of sexual activity is necessary to avoid complications like myocardial infarction. This misconception worsens quality of life of patient which is already limited. In this kind of situations, a physician is supposed to answer lots of questions. Patient's risk status should be interpreted and stratified by further examinations, before deciding to treat. Pharmacological and rehabilitative modalities can be applied when indicated, on the other hand, majority of the patients are classified as low risk status that are assumed to be safe. A routine follow- up is recommended for this kind of patients by 6 months intervals, regardless the patient is under medication or not.

Evaluation of the effect on patient parameters of not monitoring gastric residual volume in intensive care patients on a mechanical ventilator receiving enteral feeding: A randomized clinical trial.

PURPOSE: This study aimed to evaluate the effects of not measuring gastric residual volume (GRV) in intensive care patients on a mechanical ventilator and receiving enteral feeding on the feeding intolerance, gastroesophageal reflux (GER) risk, and nutritional adequacy. METHODS: This randomized clinical study was performed in 2 medical intensive care units of 2 university hospitals in Ankara, Turkey. The patients were randomized into 2 groups. In the group with GRV monitoring, GRV was measured 3 times a day, and the GRV threshold was accepted as 250 mL. In addition, 24-hour pH monitoring was used in this group to assess the risk of GER. In the group without GRV monitoring, GRV was not measured. The patients were followed-up for 5 days. RESULTS: The feeding targets were reached more quickly in the group without GRV monitoring (n = 26) with no increase in the complication rate (P < .05). No significant relationship was found between GRV and GER in the group with GRV monitoring (n = 25) (P > .05). CONCLUSION: The discrepancies in GRV measurement make it unreliable for monitoring feeding intolerance and GER. The use of GRV measurements may therefore be discontinued as part of the standard care protocol in medical intensive care units.

Oxidative stress status in familial Mediterranean fever with or without proteinuria.

Although several studies have indicated oxidative system abnormalities in patients with familial Mediterranean fever, it is still obscure whether proteinuria seen in this disease has an effect on the oxidative system. In the present study, oxidative system changes were investigated in familial Mediterranean fever with or without proteinuria. Plasma malondialdehyde levels in proteinuric and nonproteinuric patients were higher than those of the controls and they were also significantly higher in the patients with proteinuria compared to patients without proteinuria. The patients had significantly lower plasma glutathione peroxidase activities than the controls. Glutathione peroxidase activities did not show statistically significant differences between the patients with and those without proteinuria. A significant difference was not established for erythrocyte superoxide dismutase activities. These data suggest that there is an increase in lipid peroxidation in familial Mediterranean fever. Decreased plasma glutathione peroxidase activities seem to be responsible for increased plasma malondialdehyde levels in both patient groups. However, the fact that higher plasma malondialdehyde levels in proteinuric patients were observed compared to nonproteinuric patients in the presence of the unchanged plasma glutathione peroxidase activities in these groups suggests that the nephrotic state may have a contribution to this situation.

Hyperbaric oxygen-induced changes in bacterial translocation and acinar ultrastructure in rat acute necrotizing pancreatitis.

BACKGROUND: We aimed to investigate the effects of hyperbaric oxygen therapy on bacterial translocation and acinar cell ultrastructure in a rat model of acute necrotizing pancreatitis. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into three groups. Acute pancreatitis was induced in groups II and III. Groups I and II did not receive any treatment, and group III was treated with hyperbaric oxygen. All surviving animals were killed 48 h after the induction of pancreatitis. Bacterial translocation and histological and ultrastructural changes were determined. RESULTS: The incidence of bacterial translocation in group III was significantly lower in comparison with group II (P<0.001). Histopathological and ultrastructural injury scores were also significantly lower in group III (P<0.001 and P<0.04, respectively). CONCLUSIONS: Hyperbaric oxygen therapy displayed beneficial effects on pancreatic superinfection and or histopathological and ultrastructural changes in experimental necrotizing pancreatitis.

The effect of activated protein C on experimental acute necrotizing pancreatitis.

INTRODUCTION: Acute pancreatitis is a local inflammatory process that leads to a systemic inflammatory response in the majority of cases. Bacterial contamination has been estimated to occur in 30-40% of patients with necrotizing pancreatitis. Development of pancreatic necrosis depends mainly on the degree of inflammation and on the microvascular circulation of the pancreatic tissue. Activated protein C (APC) is known to inhibit coagulation and inflammation, and to promote fibrinolysis in patients with severe sepsis. We investigated the effects of APC on histopathology, bacterial translocation, and systemic inflammation in experimental acute necrotizing pancreatitis. MATERIALS AND METHOD: Forty-five male Sprague-Dawley rats were studied. Rats were randomly allocated to three groups. Acute pancreatitis was induced in group II (positive control; n = 15) and group III (treatment; n = 15) rats by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham; n = 15) received an injection of normal saline into the common biliopancreatic duct to mimic a pressure effect. Group III rats were treated with intravenous APC 6 hours after induction of pancreatitis. Pancreatic tissue and blood samples were obtained from all animals for histopathological examination and assessment of amylase, tumor necrosis factor-alpha, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured. RESULTS: Acute pancreatitis developed in all groups apart from group I (sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Histopathological pancreatitis scores in the APC-treated group were lower than in positive controls (10.31 +/- 0.47 versus 14.00 +/- 0.52; P < 0.001). Bacterial translocation to mesenteric lymph nodes and to pancreas in the APC-treated group was significantly decreased compared with controls (P < 0.02 and P < 0.007, respectively). Serum amylase, tumor necrosis factor-alpha, and IL-6 levels were also significantly decreased in comparison with positive controls (P < 0.001, P < 0.04 and P < 0.001, respectively). CONCLUSION: APC improved the severity of pancreatic tissue histology, superinfection rates and serum markers of inflammation during the course of acute necrotizing pancreatitis.

Paraoxonase 1 Activity and Survival in Sepsis Patients.

BACKGROUND: Sepsis is a state of augmented oxidative stress and diminished antioxidant capacity. High density lipoprotein (HDL) particles were shown to possess antioxidant and anti-inflammatory properties, as well as Paraoxonase 1 (PON1), which is an enzyme that is also protective against HDL oxidation. Previous studies suggested a possible role of decreased PON1 activity or HDL levels in sepsis patients. AIMS: The present study was designed to test a hypothesis that higher PON1 activity and HDL-cholesterol levels could predict a better survival in sepsis patients. STUDY DESIGN: Observational study. METHODS: Venous blood samples were collected from sepsis patients for HDL-cholesterol levels, PON1 activity and cytokine assays (TNF-α and IL-6) and Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores were calculated in order to weight patients' disease severity on the day of sepsis diagnosis. Patients were followed-up until the 28(th) day for any cause intra-hospital mortality. Data were statistically analyzed for effects of study parameters on patients' survival. RESULTS: In total, 85 patients with sepsis were included in the study. The mean age was 65.2±17.9 years and 48 were male; at the end of the 28-day follow-up period, 46 survived. TNF-α (86.9±10.5 vs 118.6±16.4) and IL-6 levels (906.7±82.7 vs 1323.1±54.3) were significantly higher in non-survivors, while PON1 activity (140.7±42.3 vs 66.7±46.6) and HDL-cholesterol levels (43.6±8.1 vs 34.5±8.9) were significantly higher in survivors (p<0.001 for all). TNF-α (r=-0.763) and IL-6 levels (r=-0.947) showed strong negative correlations, PON1 activity (r=0.644) and HDL-cholesterol levels (r=0.477) showed positive correlations with patient survival (p<0.001 for all). Survival estimates significantly favored TNF-α (Log Rank 59.5, p<0.001) and IL-6 levels (Log Rank 53.2, p<0.001) according to PON1 activity (Log Rank 5.4, p<0.03) and HDL-cholesterol levels (Log Rank 8.3, p<0.005). Regression analyses for relative contributions of parameters to survival showed that higher IL-6 levels (t: -16.489, p<0.001) were the most significant negative factor for survival, and TNF-α levels (t: -4.417, p<0.001), whereas PON1 activity had a positive effect (t:3.210, p<0.003). CONCLUSION: The present study showed that although low PON1 activity and HDL-cholesterol levels were related to mortality, higher levels were not found to be as predictive as cytokine levels for survival.

A new combination therapy in severe acute pancreatitis--hyperbaric oxygen plus 3-aminobenzamide: an experimental study.

OBJECTIVES: This study was designed to evaluate effects of hyperbaric oxygen (HBO) plus 3-aminobenzamide (3-AB) cotreatment on tissue oxidative stress parameters (TOSp), tissue histopathology scores (THSc), and bacterial translocations (Bact-Trans) in an experimental model of severe acute pancreatitis (AP). METHODS: Seventy-five Sprague-Dawley rats were randomized into 5 groups. Group 1 received sham. Severe AP was induced by intraductal taurocholate infusion and then group 2 received saline, group 3 received 3-AB, group 4 received 3-AB plus HBO, and group 5 received HBO. 3-Aminobenzamide (10 mg/kg per day, once daily, intraperitoneal) and saline (1 mL/kg) were started right after the induction, whereas HBO (2,8 atm pressure, BID, 90 minutes each) was started at the sixth hour. The rats were euthanized at the 54th hour, and TOSp, THSc, and Bact-Trans were studied. RESULTS: In treatment groups 3 and 5, Bact-Trans (P < 0.05, P < 0.05), TOSp (P < 0.05, P < 0.05), and THSc (P < 0.001, P < 0.001) were significantly lower than controls. In addition to these findings, group 4 (cotreatment) showed the most significant effect on Bact-Trans and THSc (P < 0.001, P < 0.001) and also better in TOSp (P < 0.02). CONCLUSIONS: Poly(ADP-ribose) polymerase inhibition by 3-AB and HBO treatment alone was effective in the course of severe AP, and favorable with cotreatment because of the improved cascades of inflammatory process by different aspects.