High-Resolution Plasma Metabolomics and Thiamine Status in Critically Ill Adult Patients.

Background and Aim: Thiamine (Vitamin B1) is an essential micronutrient and a co-factor for metabolic functions related to energy metabolism. We determined the association between whole blood thiamine pyrophosphate (TPP) concentrations and plasma metabolites using high resolution metabolomics in critically ill patients. Methods: Cross-sectional study performed in Erciyes University Hospital, Kayseri, Turkey and Emory University, Atlanta, GA, USA. Participants were ≥ 18 years of age, with an expected length of ICU stay longer than 48 hours, receiving furosemide therapy for at least 6 months before ICU admission. Results: Blood for TPP and metabolomics was obtained on the day of ICU admission. Whole blood TPP concentrations were measured using high-performance liquid chromatography (HPLC). Liquid chromatography/mass spectrometry was used for plasma high-resolution metabolomics. Data was analyzed using regression analysis of TPP levels against all plasma metabolomic features in metabolome-wide association studies. We also compared metabolomic features from patients in the highest TPP concentration tertile to patients in the lowest TPP tertile as a secondary analysis. We enrolled 76 participants with a median age of 69 (range, 62.5-79.5) years. Specific metabolic pathways associated with whole blood TPP levels, using both regression and tertile analysis, included pentose phosphate, fructose and mannose, branched chain amino acid, arginine and proline, linoleate, and butanoate pathways. Conclusions: Plasma high-resolution metabolomics analysis showed that whole blood TPP concentrations are significantly associated with metabolites and metabolic pathways linked to the metabolism of energy, amino acids, lipids, and the gut microbiome in adult critically ill patients.

Gut barrier protein levels in serial blood samples from critically ill trauma patients during and after intensive care unit stay.

PURPOSE: In an effort to better manage critically ill patients hospitalised in the intensive care unit (ICU) after experiencing multiple traumas, the present study aimed to assess whether plasma levels of intestinal epithelial cell barrier proteins, including occludin, claudin-1, junctional adhesion molecule (JAM-1), tricellulin and zonulin, could be used as novel biomarkers. Additional potential markers such as intestinal fatty acid-binding protein (I-FABP), D-lactate, lipopolysaccharide (LPS) and citrulline were also evaluated. We also aimed to determine the possible relationships between the clinical, laboratory, and nutritional status of patients and the measured marker levels. METHODS: Plasma samples from 29 patients (first, second, fifth and tenth days in the ICU and on days 7, 30 and 60 after hospital discharge) and 23 controls were subjected to commercial enzyme-linked immunosorbent assay (ELISA) testing. RESULTS: On first day (admission) and on the second day, plasma I-FABP, D-lactate, citrulline, occludin, claudin-1, tricellulin and zonulin levels were high in trauma patients and positively correlated with lactate, C-reactive protein (CRP), number of days of ICU hospitalisation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score and daily Sequential Organ Failure Assessment (SOFA) scores (P < 0.05-P < 0.01). CONCLUSION: The results of the present study showed that occludin, claudin-1, tricellulin and zonulin proteins, as well as I-FABP, D-lactate and citrulline, may be used as promising biomarkers for the evaluation of disease severity in critically ill trauma patients, despite the complexity of the analysis of various barrier markers. However, our results should be supported by future studies.

Evaluation of whole blood thiamine pyrophosphate concentrations in critically ill patients receiving chronic diuretic therapy prior to admission to Turkish intensive care units: A pragmatic, multicenter, prospective study.

BACKGROUND/OBJECTIVES: Thiamine plays a pivotal role in energy metabolism. The aim of the study was to determine serial whole blood TPP concentrations in critically ill patients receiving chronic diuretic treatment before ICU admission and to correlate TPP levels with clinically determined serum phosphorus concentrations. SUBJECTS/METHODS: This observational study was performed in 15 medical ICUs. Serial whole blood TPP concentrations were measured by HPLC at baseline and at days 2, 5 and 10 after ICU admission. RESULTS: A total of 221 participants were included. Of these, 18% demonstrated low TPP concentrations upon admission to the ICU, while 26% of participants demonstrated low levels at some point during the 10-day study period. Hypophosphatemia was detected in 30% of participants at some point during the 10-day period of observation. TPP levels were significantly and positively correlated with serum phosphorus levels at each time point (P < 0.05 for all). CONCLUSIONS: Our results show that 18% of these critically ill patients exhibited low whole blood TPP concentrations on ICU admission and 26% had low levels during the initial 10 ICU days, respectively. The modest correlation between TPP and phosphorus concentrations suggests a possible association due to a refeeding effect in ICU patients requiring chronic diuretic therapy.

Gastric ultrasound, citrulline, and intestinal fatty acid-binding protein as markers of gastrointestinal dysfunction in critically ill patients: A pilot prospective cohort study.

BACKGROUND: Gastrointestinal (GI) dysfunction is common in the intensive care unit (ICU), although there is no consensus on biomarkers of GI dysfunction. We aimed to evaluate ultrasound-based gastric antrum measurements and serum intestinal fatty acid-binding protein (IFABP) and citrulline levels in relation to GI dysfunction in critically ill patients. METHODS: Adult critically ill patients receiving enteral nutrition and stayed for in the ICU for ≥48 h was included. GI dysfunction was described using Gastrointestinal Dysfunction Score (GIDS). Gastric antrum measurements, including craniocaudal (CC) diameter, anteroposterior diameter, and antral-cross sectional area (CSA), as well as serum levels for IFABP and citrulline, were prospectively recorded at baseline and on day 3 and day 5 of enteral nutrition. The receiver operating characteristic (ROC) analysis was performed to evaluate gastric ultrasound parameters, serum IFABP, and citrulline concentrations in predicting GI dysfunction. RESULTS: Thirty-nine participants with a median age of 60 years were recruited and 46.2% of participants had GI dysfunction. ROC analysis revealed that the cutoff value of CSA score to predict GI dysfunction was 4.48 cm2 , which provided 72.7% sensitivity and 77.2% specificity (area under the curve = 0.768, 95% CI: 0.555-0.980). At baseline, gastric residual volume was highly correlated with CC diameter and CSA (r = 0.764, P < 0.001 and r = 0.675, P < 0.001, respectively). Serum IFABP and citrulline levels had no correlation with GI dysfunction or gastric ultrasound parameters (P > 0.05). CONCLUSION: CSA was associated with GI dysfunction in critically ill patients. Serum IFABP and citrulline concentrations were poor in predicting GI dysfunction.

Enteral nutrition interruptions in critically ill patients: A prospective study on reasons, frequency and duration of interruptions of nutritional support during ICU stay.

BACKGROUND & AIMS: Enteral Nutrition (EN) may be interrupted due to various reasons in the setting of intensive care unit (ICU) care. This study aimed to investigate the reasons, frequency, and duration of EN interruptions in critically ill patients within the first 7 days of ICU stay. METHODS: A total of 122 critically ill patients (median age: 63 years, 57% were males) initiating EN within the first 72 h of ICU admission and continued EN for at least 48 h during ICU stay were included in this observational prospective study conducted at a Medical ICU. Patients were followed for hourly energy intake as well as the frequency, reason, and duration of EN interruptions, for the first seven nutrition days of ICU stay or until death/discharge from ICU. RESULTS: The median APACHE II score was 22 (IQR, 17-27). The per patient EN interruption frequency was 2.74 and the median total EN interruption duration was 960 (IQR, 105-1950) minutes. The most common reason for EN interruption was radiological procedures (91 episodes) and the longest duration of EN interruption was due to tube malfunctions (1230 min). Target energy intake were achieved on the 6th day at a maximum rate of 89.4%. Logistic regression showed that there was relationship between increased mortality and patients with ≥3 EN interruptions (OR: 6.73 (2.15-30.55), p = 0.004) after adjusting for confounding variables (age and APACHE II score). According to Kaplan Meier analysis, patients with ≥3 EN interruptions had significantly lower median survival times than patients with <3 EN interruptions (24.0 (95% CI 8.5-39.5) vs 18.0 (95% CI 13-23) days, p = 0.014). CONCLUSION: During the first week of EN support, the most common reason of EN interruptions was related to radiological procedures and the longest EN interruptions was due to feeding tube malfunctions. There was relationship between ≥3 EN interruptions and increased mortality.

Serum micronutrient levels in critically ill patients receiving continuous renal replacement therapy: A prospective, observational study.

BACKGROUND: Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) may deplete micronutrient levels. Patients are also at risk for micronutrient depletion due to underlying illness(s), poor nutrient intake prior to intensive care unit (ICU) admission and/or increased requirements. We determined vitamin and trace element status before, during and after CRRT in critically ill patients. METHODS: This prospective observational study performed in mixed medical and surgical ICU patients. Serial serum vitamin B6 and vitamin C concentrations were measured by HPLC and folic acid by ECLIA. Serum chromium, copper, selenium, and zinc were measured using ICP-MS. Serum ceruloplasmin was measured by the Erel method. RESULTS: Fifty adult ICU patients with AKI were recruited. The median APACHE II score on ICU admission was high at 24.0 (6.0-33.0). The median days on CRRT was 2.0 (2.0-4.0) days. At baseline (within 10-15 minutes of CRRT initiation), serum vitamin C, selenium and zinc were below normal. Serum vitamin B6 levels at 72 hours on CRRT were significantly lower than at 24 hours (p = 0.011). Serum vitamin C values fell significantly at 24 and 72 hours during CRRT (p = 0.030 and p = 0.001), respectively, and remained low 24 and 48 hours after CRRT was stopped (p = 0.021). At baseline and during CRRT, 96% of participants had at least two or more micronutrient levels below the normal range. CONCLUSION: Serum vitamin C, selenium and zinc concentrations were below the normal range at baseline. CRRT was associated with a significant further decrease in levels of vitamin C, selenium and zinc.

Measurement of serial serum total and acylated ghrelin levels in critically ill patients: A prospective and observational pilot study.

BACKGROUND: Ghrelin is a hormone that regulates appetite and energy metabolism. The change of serial serum total and acylated ghrelin levels during hospital stays of critical patients are unknown. In addition, the relationship of this change with the clinical results of patients in the intensive care unit (ICU) is also unknown. The aim of this study was to determine serum total and acylated ghrelin levels serially in critically ill patients. METHODS: This prospective study was performed in the ICU. Patients who were >18 years old and stayed in ICU for >48 h were included in the study. Serum total and acylated ghrelin concentrations were measured at baseline in all participants and serially on the 2nd, 5th, and 10th day after entry into the study in those who remained in the ICU. RESULTS: A total of 60 participants were included. The mean age was 56 ± 21 years. (Baseline, 2nd, 5th, and 10th day median serum total ghrelin levels were 3551 (1651-3995), 3485.20 (1379-4071), 3359 (1167-3919), and 3355 pg/ml (2207-3843), respectively. Baseline, 2nd, 5th, and 10th day acylated ghrelin levels were 47 (0-673), 50 (0-730), 73 (0-808), and 125 pg/ml (0-689), respectively. There was no significant difference between total ghrelin/acylated ghrelin levels and mortality (P > .05). ICU mortality was 30%. CONCLUSION: Ghrelin levels were decreased slightly and acylated ghrelin levels increased substantially over time in critically ill patients. There were no differences between serum total ghrelin/acylated ghrelin levels and ICU mortality .

Clinical Outcomes and Independent Risk Factors for 90-Day Mortality in Critically Ill Patients with Respiratory Failure Infected with SARS-CoV-2: A Multicenter Study in Turkish Intensive Care Units.

BACKGROUND: There are limited data on the long-term outcomes of COVID-19 from different parts of the world. AIMS: To determine risk factors of 90-day mortality in critically ill patients in Turkish intensive care units (ICUs), with respiratory failure. STUDY DESIGN: Retrospective, observational cohort. METHODS: Patients with laboratory-confirmed COVID-19 and who had been followed up in the ICUs with respiratory failure for more than 24 hours were included in the study. Their demographics, clinical characteristics, laboratory variables, treatment protocols, and survival data were recorded. RESULTS: A total of 421 patients were included. The median age was 67 (IQR: 57-76) years, and 251 patients (59.6%) were men. The 90-day mortality rate was 55.1%. The factors independently associated with 90-day mortality were invasive mechanical ventilation (IMV) (HR 4.09 [95% CI: [2.20-7.63], P < .001), lactate level >2 mmol/L (2.78 [1.93-4.01], P < .001), age ≥60 years (2.45 [1.48-4.06)], P < .001), cardiac arrhythmia during ICU stay (2.01 [1.27-3.20], P = .003), vasopressor treatment (1.94 [1.32-2.84], P = .001), positive fluid balance of ≥600 mL/day (1.68 [1.21-2.34], P = .002), PaO2/FiO2 ratio of ≤150 mmHg (1.66 [1.18-2.32], P = .003), and ECOG score ≥1 (1.42 [1.00-2.02], P = .050). CONCLUSION: Long-term mortality was high in critically ill patients with COVID-19 hospitalized in intensive care units in Turkey. Invasive mechanical ventilation, lactate level, age, cardiac arrhythmia, vasopressor therapy, positive fluid balance, severe hypoxemia and ECOG score were the independent risk factors for 90-day mortality.

Serum trace elements levels in patients transferred from the intensive care unit to wards.

BACKGROUND & AIMS: Trace elements act as co-factors and/or in co-enzymes in many metabolic pathways and its deficiency contributes to metabolic and infectious complications. The aim of this study was to determine serum zinc, selenium, cobalt, chromium, copper and ceruloplasmin levels for identify the need for post intensive care unit (ICU) nutritional follow-up. METHODS: This study was prospectively conducted in medical ICU. Adult patients (≥18 years) who stayed in ICU more than 48 h and transferred to ward were included in the study. Blood samples of trace element levels were sampled at discharge. RESULTS: We enrolled 100 patients. The median age was 60 (40-70) years with Acute Physiology and Chronic Health Evaluation II (APACHE II) score 15 (11-21) . The median C-Reactive Protein (CRP) level was 53.9 (24.8-116.0) mg/L at discharge. Median serum zinc (24.4 mcg/dl:14.2-38.7) and chromium (0.22 mcg/dl:0.17-0.34) levels were below reference values, while median copper (111.9 (73.0-152.5) mcg/dl) and selenium (54.8 (36.4-95.25) mcg/L) values were within ranges. Serum concentrations of chromium, zinc, and selenium were lower than the normal values in 98, 90, and 36% of patients, respectively. The 28-day ICU mortality were correlated with low serum selenium levels (p = 0.03). CONCLUSION: Serum chromium and zinc levels were below reference values at discharge, but this finding was in context of inflammation. Low serum selenium level observed in 36% was associated to 28-day ICU mortality.

The use of high-flow nasal oxygen vs. standard oxygen therapy in hematological malignancy patients with acute respiratory failure in hematology wards

Background/aim: High flow nasal cannula (HFNC) was mostly used in intensive care units (ICUs) with few studies in other departments. We hypothesized that HFNC applied at wards is beneficial for acute respiratory failure in hematological malignancy patients. Materials and methods: The study is a single center, randomized controlled study. Inclusion criteria were hypoxemic respiratory failure and hematological malignancy. Patients were randomized to either venturi mask/nasal cannula oxygen treatment or HFNC. Results: One hundred patients were included in the study. Median age was 58.5 (18­86) years and APACHE II score was 17 (5­29). HFNC group was 51 patients and the oxygen treatment group 49 patients. P/F ratios were similar between the groups throughout the study period. Endotracheal intubation was required in 10 (20.0%) patients in oxygen group and 17 (33.0%) patients in HFNC group (p = 0.14). A total of 17 (35.0%) patients in oxygen group and 17 (33.0%) patients in HFNC group received noninvasive mechanical ventilation (p = 0.97). Median VAS comfort scores at the 2nd and 24th hours were not different between groups. The 28-day mortality rate was 36.7% (18 deaths) in the standard group and 45.0% (23 deaths) in the HFNC group (p = 0.39). Conclusion: HFNC applied in wards is not superior to standard oxygen treatment for acute respiratory failure in hematological malignancy patients.

A case of Crimean-Congo hemorrhagic fever with the bacteremia of Clostridium perfringens.

Crimean-Congo hemorrhagic fever (CCHF) is a worldwide tick-borne viral infection in humans. The aim of the study is to report a case of a female patient with severe CCHF with the bacteremia of Clostridium perfringens. An 18-year-old woman admitted to the emergency department with sudden onset of fever, nausea and vomiting, myalgia, headache, generalized abdominal pain. It was learned that the patient was living in a rural area and had a history of tick bite 3 days before the admission. At laboratory examination, bicytopenia, abnormal liver function tests, and abnormal coagulation parameters were observed. The diagnosis of the case was confirmed with a positive real-time polymerase chain reaction. On the third day of hospitalization, she had an increase in abdominal pain, confusion, and respiratory distress. She was transferred to the intensive care unit for close monitoring. On the fifth day of hospitalization, she developed fever again. Catheter and peripheral anaerobic blood cultures grew C. perfringens. No evidence of perforation was observed on abdominal tomography. It has been successfully treated with a multidisciplinary approach. CCHF demonstrates different types of clinical presentations, except for common symptoms of fever and hemorrhage. A case of CCHF with C. perfringens bacteremia has not been previously reported before.

Effects of oral/enteral nutrition alone versus plus pantoprazole on gastrointestinal bleeding in critically ill patients with low risk factor: a multicenter, randomized controlled trial

Background/aim: Critically ill patients are at risk of developing gastrointestinal (GI) bleeding due to stress causing mucosal damage. Aim of the study was to determine the effect of oral/enteral nutrition with or without concomitant pantoprazole on upper GI bleeding in low risk critically ill patients. Materials and methods: This was a prospective, randomized, open-label, multicenter study conducted with intensive care unit (ICU) patients receiving oral/enteral nutritional support. Patients were randomly assigned into two groups including intervention group (received oral/EN plus pantoprazole) and control group (received only oral/EN). Results: A total of 300 patients (intervention group: 152, control group: 148) participated in the study. Overall, 226 (75%) patients were fed by orally and 74 (25%) patients fed by enteral tube feeding. Median duration of nutritional support 4 (range: 2­33) days. Overt upper GI bleeding was noted only in one patient (0.65%) who was in the intervention group. The overall length of ICU stay of 4 (2­105) days, while ICU stay was significantly longer in the intervention group than in the control group (P = 0.006). Conclusions: Our findings seems to indicate that in patients who are at low risk for GI bleeding and under oral/enteral nutritional support, the use of PPIs may not reduce the risk of bleeding, however these results are imprecise because of low event (GI bleeding) rate and limited power.

Thiamin Status in Adults Receiving Chronic Diuretic Therapy Prior to Admission to a Medical Intensive Care Unit: A Pilot Study.

BACKGROUND: The aim of the study was to determine serum thiamin concentrations in critically ill medical patients who required chronic diuretic drug treatment before admission to a medical intensive care unit (ICU). METHODS: This prospective study was performed in a medical ICU. Subjects who received diuretic drug therapy for at least 6 months prior to ICU admission constituted the diuretic group. The control group was clinically matched adults admitted to the same ICU but without a history of diuretic therapy. RESULTS: A total of 50 subjects were included (25 subjects in each of the diuretic and control groups). In the diuretic group, daily dose of furosemide prior to admission was 40 mg/d (range of 20-160 mg/d). In all subjects, the ICU admission baseline blood thiamin concentrations were 31.2 ± 27.1 ng/mL. In the diuretic group, the baseline whole blood thiamin level was significantly lower compared with levels in the control group (15.5 ± 10.7 vs 46.8 ± 29.5 ng/mL; P < 0.001). On day 2 after entry, thiamin levels remained low (23.2 ± 15.4 ng/mL in the diuretic group vs 49 ± 38 ng/mL in the control group; P = 0.003). Low thiamin levels were found in 96% of patients at baseline and in 72% of patients on the second day in the diuretic group. CONCLUSION: Adults receiving chronic diuretic therapy and then requiring medical ICU care commonly exhibit thiamin depletion on admission to the ICU and during the initial days of ICU care.

Risk factors for noncatheter-related Candida bloodstream infections in intensive care units: A multicenter case-control study.

Candida bloodstream infections are associated with high mortality among critically ill patients in intensive care units (ICUs). Studies that explore the risk factors for candidemia may support better patient care in intensive care units. We conducted a retrospective, multicenter case-control study to investigate the risk factors for noncatheter-related Candida bloodstream infections (CBSI) in adult ICUs. Participants selected controls randomly on a 1:1 basis among all noncase patients stayed during the same period in ICUs. Data on 139 cases and 140 controls were deemed eligible. Among the controls, 69 patients died. The stratified Fine-Gray model was used to estimate the subdistribution Hazard ratios. The subdistribution hazards and 95% confidence intervals for final covariates were as follows: prior exposure to antimycotic agents, 2.21 (1.56-3.14); prior exposure to N-acetylcysteine, 0.11 (0.03-0.34) and prior surgical intervention, 1.26 (0.76-2.11). Of the patients, those exposed to antimycotic drugs, 87.1% (54/62) had breakthrough candidemia. Serious renal, hepatic, or hematologic side effects were comparable between patients those exposed and not-exposed to systemic antimycotic drugs. Untargeted administration of antimycotic drugs did not improve survival among candidemic patients (not-exposed, 63.6% [49/77]; exposed % 66.1 [41/62]; P = .899). This study documented that exposure to an antifungal agent is associated with increased the risk of subsequent development of CBSIs among nonneutropenic adult patients admitted to the ICU. Only two centers regularly prescribed N-acetylcysteine. Due to the limited number of subjects, we interpreted the positive effect of N-acetylcysteine on the absolute risk of CBSIs with caution.

Current Statement of Intensive Care Units in Turkey: Data obtained from 67 Centers.

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.

MDR1 single nucleotide polymorphism C3435T in Turkish patients with non-small-cell lung cancer.

We assessed whether single nucleotide polymorphisms (SNPs) in MDR1 gene C3435T predicted the outcome of platinum-based chemotherapies and survival in our non small cell lung cancer (NSCLC) patients. A total of 79 non-small cell lung cancer patients were enrolled to study. We determined the MDR1 C3435T single nucleotide gene polymorphisms. Median age was 60years: 91.7% male, 8.9% female. We found that CC, CT, TT genotype and T, C allele frequencies in lung cancer patients as 24.1%, 62%, 13.9% and 44.3%, 55.7%, respectively. Patients with CT genotype had a higher response rate (11.4%) than the other genotypes. However, this difference is not statistically significant (p=0.743). Cox regression analysis for overall survival showed that ECOG PS status 0 (HR PS 1 vs. 0, 5.68 p=0.002; HR of PS 2 vs. 0 is 21.579, p=0.001; HR of PS 3 vs. 0 is 35.35, p=0.001), stage ≤II (HR of stage III vs. I+II is 17.77; p=0.016, HR of stage IV vs. I+II is 26.97, p=0.006), and albumin level ≥3g/dl (HR of albumin <3g/dl vs. ≥3g/dl is 2.46, p=0.044) were the most important prognostic factors (also, time to progression was related to these factors). There was no significant association between the genotypes and clinicopathologic parameters; however, good performance status, early stage and ≥3g/dl albumin level were found to be the most important prognostic factors for overall survival and progression-free survival.