The effects of L-carnitine supplementation on inflammation, oxidative stress, and clinical outcomes in critically Ill patients with sepsis: a randomized, double-blind, controlled trial.

BACKGROUND: Sepsis, a life-threatening organ dysfunction caused by a host's dysregulated response to infection with an inflammatory process, becomes a real challenge for the healthcare systems. L-carnitine (LC) has antioxidant and anti-inflammatory properties as in previous studies. Thus, we aimed to determine the effects of LC on inflammation, oxidative stress, and clinical parameters in critically ill septic patients. METHODS: A randomized double-blinded controlled trial was conducted. A total of 60 patients were randomized to receive LC (3 g/day, n = 30) or placebo (n = 30) for 7 days. Inflammatory and oxidative stress parameters (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), superoxide dismutase (SOD), malondialdehyde (MDA), total antioxidant capacity (TAC), 28-day mortality rate, and some monitoring variables were evaluated. RESULTS: There was no statistically significant difference between study arms in baseline characteristics and disease severity scores. CRP (p < 0.001) and ESR (p: 0.004) significantly reduced, and SOD (p < 0.001) and TAC (p < 0.001) significantly improved in the LC group after 7 days. Between-group analysis revealed a significant reduction in CRP (p: 0.001) and serum chloride (p: 0.032), an increase in serum albumin (p: 0.036) and platelet (p: 0.004) significantly, and an increase in SOD marginally (p: 0.073). The 28-day mortality rate was also lower in the LC group compared with placebo (7 persons vs. 15 persons) significantly (odds ratio: 0.233, p: 0.010). CONCLUSIONS: L-carnitine ameliorated inflammation, enhanced antioxidant defense, reduced mortality, and improved some clinical outcomes in critically ill patients with sepsis. TRIAL REGISTRATION: IRCT20201129049534N1; May 2021.

MicroRNA profiles in critically ill patients.

The use of biomarkers to expedite diagnosis, prognostication, and treatment could significantly improve patient outcomes. The early diagnosis and treatment of critical illnesses can greatly reduce mortality and morbidity. Therefore, there is great interest in the discovery of biomarkers for critical illnesses. Micro-ribonucleic acids (miRNAs) are a highly conserved group of non-coding RNA molecules. They regulate the expression of genes involved in several developmental, physiological, and pathological processes. The characteristics of miRNAs suggest that they could be versatile biomarkers. Assay panels to measure the expression of several miRNAs could facilitate clinical decision-making for a range of diseases. We have, in this paper, reviewed the current understanding of the role of miRNAs as biomarkers in critically ill patients.

Evaluation of Curcumin-Piperine Supplementation in COVID-19 Patients Admitted to the Intensive Care: A Double-Blind, Randomized Controlled Trial.

BACKGROUND: Curcumin is a traditional remedy for diseases associated with hyper-inflammatory responses and immune system impairment. Piperine, a bioactive compound in black pepper, has the potential to enhance curcumin bioavailability. 0This study aims to examine the effect of the curcumin-piperine co-supplementation in patients infected with SARS-CoV-2 and admitted to the intensive care unit (ICU). MATERIAL AND METHODS: In this parallel randomized, double-blind, placebo-controlled trial, 40 patients with COVID-19 admitted to ICU were randomized to receive three capsules of curcumin (500 mg)-piperine (5 mg) or placebo for 7 days. RESULTS: After 1 week of the intervention, serum aspartate aminotransferase (AST) (p = 0.02) and C-reactive protein (CRP) (p = 0.03) were significantly decreased, and hemoglobin was increased (p = 0.03) in the curcumin-piperine compared to the placebo group. However, compared with the placebo, curcumin-piperine had no significant effects on the other biochemical, hematological, and arterial blood gas and 28-day mortality rate was three patients in each group (p = 0.99). CONCLUSION: The study results showed that short-term curcumin-piperine supplementation significantly decreased CRP, AST, and increased hemoglobin in COVID-19 patients admitted to the ICU. Based on these promising findings, curcumin appears to be a complementary treatment option for COVID-19 patients, although some parameters were not affected by the intervention.

The Effect of Ipratropium Bromide with Violet Flower Extract, Ipratropium Bromide with Budesonide, and Ipratropium Bromide Alone on the Cuff-Leak of the Endotracheal Tube in Intubated ICU Patients.

Background: The aim of the present study was to evaluate the effect of ipratropium bromide with violet flower extract, ipratropium bromide with budesonide, and ipratropium bromide alone on the cuff-leak of the endotracheal tube and changes in hemodynamic parameters in intubated patients admitted to the intensive care unit. Materials and Methods: The present randomized clinical trial study was performed on 195 intubated patients in three groups of 65 patients. The first group received nebulized ipratropium bromide with budesonide (I + B group), the second group in addition to ipratropium bromide, received one tablespoon of the violet flower extract syrup every 8 hours (I + V group), and the third group received nebulized ipratropium bromide alone (I group). Hemodynamic parameters and the cuff-leak ratio (CLR) of patients were evaluated up to 72 hours after intubation. Results: The results of the present study revealed that 12 hours after intubation, the mean of CLR was significantly lower in group I (with a mean of 0.14 ± 0.02) as compared with that of the I + V and I + B groups (with the means of 0.16 ± 0.05 and 0.23 ± 0.05, respectively) (P < 0.001). In addition, 24 hours after intubation, the mean of CLR in group I + V was higher than that of I + B and I groups (P < 0.05). Conclusion: According to the results of this study, the use of violet extract syrup in patients under intubation can significantly improve patients' ratio of cuff-leak and SpO2. It seems that the use of violet extract syrup is effective to prevent unwanted complications during intubation and to facilitate patients' breathing.

The Effect of Switching from Volume-Controlled to Pressure-Controlled Ventilation on Respiratory Distress and Asynchrony Index Improvement among Mechanically Ventilated Adults.

Background: It is important to synchrony the time, intensity, and respiratory signal of the phrenic nerve between the patient and the ventilator. This study aimed to evaluate the effect of switching from volume-controlled to pressure-controlled ventilation on respiratory distress and asynchrony index improvement. Materials and Methods: In this randomized controlled clinical trial, 70 patients admitted to the intensive care unit under mechanical ventilation were included. Asynchronous evaluation was performed by examining the patient and evaluating and analyzing the graphic flow curve and ventilator pressure, which included trigger and flow asynchronous and asynchronous cycling. In the intervention group, the mode of ventilation was switched to PSIMV such that peak inspiratory pressures would be equivalent to positive end-expiratory pressure (PEEP) in the volume-controlled mode. Finally, again at 60, 75, and 90 min, information about the ventilator and the patient's symptoms, and arterial carbon dioxide levels were sent by arterial gas sample. The asynchronous index was also recorded in both groups. Results: This study showed that the mean of variables such as height, ideal body weight, tidal volume, set rate; Sense, FiO2, PEEP did not differ significantly between the two groups. The mean of asynchrony was significantly reduced in both control group (16.51 ± 3.35-14.51 ± 2.90; P < 0.001) and intervention group (18.26 ± 6.13-13.32 ± 5.53; P < 0.001). Conclusion: Regardless of the type and severity of the disease, switching the ventilation mode from volume-controlled to pressure-controlled can improve patient adaptation to the ventilator, especially in cases with frequent asynchrony.

The Value of Inferior Vena Cava Ultrasonography Administration for Hypovolemia Detection in Patients with Acute Kidney Injury Hospitalized in Intensive Care Unit.

Background: The hypo-perfusion of the kidneys can lead to impairment in renal function and induce renal injury in case of delayed diagnosis and treatment. To date, laboratory markers are routinely used to determine the fluid volume status of the patients. The current study aims to evaluate the values of inferior vena cava (IVC) collapsibility index in hypovolemia diagnosis among critical patients admitted at the intensive care unit (ICU). Materials and Methods: This is a cross-sectional study performed on 67 patients admitted to the ICU due to acute kidney injury from May 2018 to October 2019. Hypovolemia was assessed assessing IVC collapsibility using ultrasonography. Laboratory data, including urine osmolality, urine-plasma creatinine ratio, sodium excretion fraction and urinary sodium level were checked. Afterward, IVC collapsibility index was measured for each patient using ultrasonography and the values of this index in accordance with the mentioned criteria was evaluated. Accordingly, reciever operating curve was depicted. Results: There was no significant asosociation between IVC collapsibility index with fractional excretion of sodium (P = 0.69), urine Na (P = 0.93) and urine osmolality ([P = 0.09]), while urine: Plasma creatinie ration revealed a significant association with IVC collapsibility index at cut point of 40.5% with sensitivity and specificity of 96% and 44% (P = 0.017, area under the curve: 0.67, 95% confidence interval: 0.551-0.804), respectively. Conclusion: According to the findings of this study, IVC collapsibility detected via ultrasonography was not an appropriate index to figure out hypovolemia in ICU patients. Furthermore, detailed studies are recommended.

Evaluation of the effectiveness of the modified nutrition risk in the critically ill (mNUTRIC) score in critically ill patients affected by COVID-19 admitted to the intensive care unit (ICU).

BACKGROUND: COVID-19 is a very harmful pandemic, and its recovery process is highly influenced by nutritional status; however, an appropriate nutritional scale has not yet been proposed for these patients. Therefore, the purpose of this study was to evaluate the effectiveness of the modified Nutrition Risk in the Critically ill (mNUTRIC) score in critically ill patients affected by COVID-19 admitted to the intensive care unit (ICU). MATERIAL AND METHODS: This was a cross-sectional study performed on 204 critically ill patients affected by COVID-19 admitted to the ICU wards. Evaluated indicators include the mNUTRIC Score as well as demographic, and biochemical indicators. RESULTS: A high percentage of COVID-19 patients (67.2%) had severe disease. Hospital and ICU stay (p > 0.001) and PH (p > 0.001) values were significantly lower in non-survivors than in survivors. mNUTRIC score (p > 0.001), PCO2 (p = 0.003), and CRP levels (p = 0.021) were significantly higher in non-survivors than survivors. mNUTRIC score had a direct correlation with age (p > 0.001), AST (p = 0.000), LDH (p = 0.026), and CRP (p = 0.014) and an inverse correlation with hospital duration (p = 0.031), albumin (p = 0.003) and PH (p < 0.001). Furthermore, there was a non-significant correlation between the mNUTRIC score and mortality chance (OR = 1.085, 95%CI [0.83, 1.42], p = 0.552). While, patients with more severe COVID-19 disease (OR = 8.057, 95%CI [1.33, 48.64], p = 0.023) and higher PCO2 (OR = 1.042, 95%CI [1.01, 1.08], p = 0.023) levels had higher odds of mortality. CONCLUSIONS: Our findings revealed that COVID-19 patients with higher CRP levels and lower PH had higher mortality and poor nutritional condition. Moreover, there was a non-significant association between the mNUTRIC score and mortality chance.

Estimating the best fraction of inspired oxygen for calculation of PaO2/FiO2 ratio in acute respiratory distress syndrome due to COVID-19 pneumonia.

Background: The ratio of partial pressure of oxygen in arterial blood (PaO2) to the fraction of inspiratory oxygen concentration (FiO2) is an indicator of pulmonary shunt fraction. PaO2/FiO2 (P/F) ratio is used to classify severity of acute respiratory distress syndrome (ARDS). With the same shunt fraction, P/F ratio decreases with increases in FiO2 which may lead to errors in classifying severity of ARDS. The effect of FiO2 on P/F ratio has not been investigated in COVID-19 pneumonia. In this study, we estimated the best FiO2 for the calculation of P/F ratio in a sample of patients with ARDS due to COVID-19 pneumonia. Materials and Methods: Blood gas and ventilatory data of 108 COVID-19 ARDS patients were analyzed in a cross-sectional observational study. Using Oxygen Status Algorithm the calculated shunt fraction served a basis for calculating P/F ratio for different FiO2. The severity of ARDS determined by P/F ratios at each FiO2s was compared with the shunt-based severity to find the optimum FiO2 for calculation of P/F ratio so the resulting classification has the best match with the reference classification. Results: A FiO2 of 1.0 for calculation of P/F ratio and ARDS classification showed the best match with shunt-based ARDS classification. A regression model was obtained with the PaO2, patient's original FiO2, Hemoglobin concentration, and SaO2 as the independent predictors of the P/F ratio for the FiO2 of 1.0. Conclusion: This study shows a FiO2 of 1.0 as the best value for correct calculation of P/F ratio and proper classification of ARDS.

Comparison of adaptive support ventilation and synchronized intermittent mandatory ventilation in patients with acute respiratory distress syndrome: A randomized clinical trial.

Background: Suitable mechanical ventilation strategies can reduce the incidence and severity of ventilator-associated lung injury in patients with acute respiratory distress syndrome (ARDS). In this study, the effects of adaptive support ventilation (ASV) and synchronized intermittent mandatory ventilation (SIMV) on respiratory parameters and arterial blood gases (ABGs) parameters were compared in ARDS patients. Materials and Methods: Twenty-four patients were randomly divided into two groups of ASV and SIMV. Patients were followed up for 3 days, and respiratory parameters including rapid shallow breathing index (RSBI), spontaneous breathing rate (SBR), minute volume, and peak inspiratory pressure (PIP) as the primary outcomes and ABG parameters including PaO2, FiO2, PaCO2, HCO3, and PaO2/FiO2 ratio as the secondary outcomes were measured. Results: PIP in patients in the SIMV group on the 1st day (P = 0.013), 2nd day (P = 0.001), and 3rd day (P = 0.004) was statistically significantly more compared to those in patients in the ASV group. RSBI, SBR, and minute volume between the ASV and SIMV groups during the 3 days were not statistically significantly different (P > 0.05). The mean arterial blood pressure, heart rate, PaO2, and PH between both groups were similar (P > 0.05). At the end of the 2nd and 3rd days, the level of FiO2 and PaCO2 in ASV was significantly lower than those in ASV group. HCO3 in each of the 3 days in the ASV group was statistically significantly lower than that in the SIMV group (P < 0.050). PaO2/FiO2 ratio in patients in the ASV group in the 3 days was statistically significantly higher than that in the SIMV group (P < 0.050). Conclusion: By reducing PIP and improving oxygenation and ABG parameters, ASV mode may be a safe and feasible mode during mechanical ventilation in patients with ARDS.

Oxidative stress and mitochondrial dysfunction following traumatic brain injury: From mechanistic view to targeted therapeutic opportunities.

Traumatic brain injury (TBI) is one of the most prevalent causes of permanent physical and cognitive disabilities. TBI pathology results from primary insults and a multi-mechanistic biochemical process, termed as secondary brain injury. Currently, there are no pharmacological agents for definitive treatment of patients with TBI. This article is presented with the purpose of reviewing molecular mechanisms of TBI pathology, as well as potential strategies and agents against pathological pathways. In this review article, materials were obtained by searching PubMed, Scopus, Elsevier, Web of Science, and Google Scholar. This search was considered without time limitation. Evidence indicates that oxidative stress and mitochondrial dysfunction are two key mediators of the secondary injury cascade in TBI pathology. TBI-induced oxidative damage results in the structural and functional impairments of cellular and subcellular components, such as mitochondria. Impairments of mitochondrial electron transfer chain and mitochondrial membrane potential result in a vicious cycle of free radical formation and cell apoptosis. The results of some preclinical and clinical studies, evaluating mitochondria-targeted therapies, such as mitochondria-targeted antioxidants and compounds with pleiotropic effects after TBI, are promising. As a proposed strategy in recent years, mitochondria-targeted multipotential therapy is a new hope, waiting to be confirmed. Moreover, based on the available findings, biologics, such as stem cell-based therapy and transplantation of mitochondria are novel potential strategies for the treatment of TBI; however, more studies are needed to clearly confirm the safety and efficacy of these strategies.

The effects of L-carnitine supplementation on inflammatory factors, oxidative stress, and clinical outcomes in patients with sepsis admitted to the intensive care unit (ICU): study protocol for a double blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Sepsis is a common cause for admission to the intensive care unit (ICU), and its incidence has been increasing. It is associated with a significant increase in serum inflammatory biomarkers such as C-reactive protein (CRP) and cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF). Sepsis is also associated with pathophysiological changes that include fluid accumulation in the lungs, eventually leading to acute respiratory distress syndrome (ARDS), tissue edema, hypotension, and acute kidney injury (AKI). Conventional therapies include antibiotics, but these may have important adverse effects, so novel therapeutic approaches are required. In animal studies, L-carnitine improves antioxidant status, and in some clinical trials, it has been shown to reduce inflammation. It has also been shown to improve respiratory distress and help maintain coenzyme A homeostasis, metabolic flexibility, promoting the normal function of the tricarboxylic acid (TCA) cycle, and oxidation of fatty acids by peroxisomes. We aim to determine the effects of very high doses of L-carnitine on inflammatory factors, oxidative stress, and clinical outcomes of patients with sepsis in ICU. METHOD AND DESIGN: In this double-blind, randomized controlled clinical trial, we will use block randomization of 60 patients with sepsis, aged between 20 and 65 years from Al-Zahra Hospital, Isfahan, Iran. The intervention group (n = 30) will receive three capsules of L-carnitine (each capsule contains 1000 mg L-carnitine; totally 3000 mg/day) for 7 days, and a control group (n = 30) will receive a placebo with the same dose and for the same duration in addition to usual care. At baseline, scores for clinical and nutritional status (Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), and NUTRIC Score) will be assessed. At beginning and end point of the study, inflammatory markers (CRP, erythrocyte sedimentation rate (ESR)), oxidative stress status (total oxidative stress (TOS), total antioxidant capacity (TAC)), and clinical variables will be evaluated also. The mortality rate will be assessed within 28 days of the beginning of the intervention. DISCUSSION: Because of the anti-inflammatory and antioxidant properties of L-carnitine, it is possible that using a high dose of 3000 mg daily of this nutritional supplement may reduce inflammation and oxidative stress and improve subsequent mortality of critically ill patients with sepsis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20201129049534N1 . Registered on 2 May 2021.

Comparison of Volume Support, Volume-Assured Pressure Support, and Spontaneous Modes in Postoperative Early Extubated Patients.

Background: This study aimed to compare respiratorily, arterial blood gas (ABG), and hemodynamics parameters among patients undergoing surgery who were admitted to intensive care unit (ICU), using three ventilation modes, including volume-assured pressure support (VAPS), volume support (VS), and spontaneous modes. Materials and Methods: One hundred and thirty-two patients were randomly assigned into three groups of VAPS, VS, and spontaneous modes utilizing randomized block procedure. Patients were followed between 12 and 30 h until extubation. Respiratory parameters including; peak inspiratory pressure (PIP), static compliance, resistance, rapid shallow breathing index (RSBI), and P 0.1(P0.1 correlates with respiratory drive and is defined as the negative pressure measured at the airway opening 100 ms after the initiation of an inspiratory effort), along with ABG parameters including; pH level, PaCO2,HCO3,PaO2/FiO2 ratio, extra hydrogen ion, and hemodynamics parameters including; mean arterial blood pressure and heart rate were measured every 3 h and compared among groups. Results: All studied parameters in three groups improved during the study. PIP, Resistance, PH, HCO3, extra hydrogen ion, PCo2, PaO2/FiO2 ratio, mean arterial blood pressure were similar among the three groups in most of the time points (P > 0.05). In most of the time points, RSBI (from 92.7 to 55.4), P 0.1 (from 6.8 to 1.7) in the VAPS group, static compliance (from 55.3 to 55.7) in the VS group, and heart rate (from 108.5 to 90.1) in spontaneous groups were significantly better than other modes (P < 0.05). Changes in RSBI, P 0.1, PCo2, HCO3, and heart rate during the study were significantly different among studied groups (P < 0.05). The length of stay in the ICU in patients who underwent VAPS was significantly shorter than the other modes. Conclusions: VAPS mode with better effects or at least as effective as VS and spontaneous modes could be select as the best mode of ventilation in postoperative early extubated patients admitted to ICU.

Evaluation of the effectiveness of the Nutritional Risk Screening System 2002 (NRS-2002) in COVID-19 patients admitted to the intensive care unit.

BACKGROUND: Nutritional status of patients with COVID-19 can affect the recovery process of patients; however, no nutritional scale was introduced to evaluate the nutritional status of the patients. Thus, the main objective of this study was to examine the usefulness of Nutritional status-2002 (NRS-2002) among COVID-19 patients admitted to the intensive care unit (ICU). MATERIAL AND METHODS: In this cross-sectional study, 73 patients with definitive corona diagnosis admitted to the ICUs of Al-Zahra hospital, Isfahan, Iran in October 2020 to January 2021 were recruited. Dietary intake, NRS-2002, demographic, anthropometric and biochemical indices of patients were recorded. RESULTS: The majority of patients were at risk for moderate (69.9%) to severe (12.3%) malnutrition. Daily calorie intake (P = .001) and albumin (P = .001) levels in deceased patients were significantly lower than the recovered group. A direct correlation between NRS-2002 and age (P < .001) and an inverse correlation with daily calorie intake (P = .002), albumin (P = .05) and PaO2 (P = .034) was found. Moreover, there is a strong correlation between NRS-2002 score and chance of death among COVID-19 patients (OR=34.5, 95%CI:(5.2 - 228.93), P-value<0.001). Likewise, the levels of bilirubin direct (OR=8, 95%CI:(1.30 - 49.38), P-value=0.025) and creatine-phosphokinase (OR=0.9, 95%CI:(0.99 - 1.00), P-value=0.035) have a significant direct association with chance of death. CONCLUSION: Results showed patients with COVID-19 admitted to the ICU did not have appropriate nutritional status and mortality was higher among patients with lower amounts of the serum albumin and daily calorie intakes. Furthermore, there is a strong association between the NRS-2002 index and the chance of mortality in these patients.

The Effect of Statins on C-Reactive Protein in Stroke Patients: A Systematic Review of Clinical Trials.

BACKGROUND: Statins reportedly have anti-inflammatory effects aside from their lipid-lowering impact. We investigated the effects of statin therapy on the level of C-reactive protein (CRP) or highly sensitive CRP (hs-CRP), a liver-derived marker of systemic inflammation, among stroke patients. METHODS: An online search was performed in Scopus, PubMed/MEDLINE, ISI Web of Science, and Google Scholar up to November 2020 to recognize clinical trials investigating the effects of statins on the CRP level in stroke patients. RESULTS: Overall, nine studies (11 treatment arms) with 1659 participants met the inclusion criteria. Six out of 9 studies (8 out of 11 arms) were categorized as studies with a high-quality methodological approach using the Cochrane Collaboration's tool. Data from 5 treatment arms indicated a significant decrease in CRP concentration, and in one treatment arm, CRP concentration did not suggest any considerable alteration following statin therapy. Moreover, two treatment arms showed a significant reduction in hs-CRP concentration and three treatment arms revealed no significant alteration in hs-CRP concentration following statin therapy. Generally, results were heterogeneous and independent of the type of statin, statin dose, treatment duration, and changes in plasma low-density lipoprotein cholesterol concentration. CONCLUSION: The results suggest that statin therapy could reduce and, therefore, could be considered in these patients as potential anti-inflammatory agents.

The clinical use of curcumin on neurological disorders: An updated systematic review of clinical trials.

Neuroprotective effects of curcumin have been shown in previous studies. This updated systematic review of clinical trials aimed to investigate the effect of curcumin on neurological disorders. Databases including PubMed, Scopus, Web of Science, and Google Scholar were systematically searched to identify clinical trials investigating the effects of curcumin/turmeric supplements alone, or in combination with other ingredients, on neurological diseases. Nineteen studies comprising 1,130 patients met the inclusion criteria. Generally, intervention and study outcomes were heterogeneous. In most of the studies, curcumin had a favorable effect on oxidative stress and inflammation. However, with the exception of AD, curcumin supplementation either alone, or in combination with other ingredients, had beneficial effects on clinical outcomes for the other aforementioned neurodegenerative diseases. For example, the frequency, severity, and duration of migraine attacks, scores on the revised ALS functional rating scale, and the occurrence of motor complications in PD were all significantly improved with curcumin supplementation either alone or in combination with other ingredients. However, in three studies, several adverse side effects (mostly gastrointestinal in nature) were reported. Curcumin supplementation may have favorable effects on inflammatory status and clinical outcomes of patients with neurological disease, although the results were not consistent.

Effect of curcumin-pipeine supplementation on clinical status, mortality rate, oxidative stress, and inflammatory markers in critically ill ICU patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This study aims to investigate the efficacy of curcumin-piperine co-supplementation on oxidative stress factors, clinical symptoms, and mortality rate in patients with coronavirus (COVID-19) admitted to the intensive care unit (ICU). TRIAL DESIGN: This study is a randomized, placebo-controlled, double-blind, parallel-arm clinical trial. PARTICIPANTS: The study participants will be recruited from patients admitted to the ICU of Al-Zahra hospital with a definitive diagnosis of COVID-19. The inclusion criteria are aged between 20 and 75 years, confirmation of COVID-19 based on the PCR test, and admitted to the ICU. The exclusion criteria include the present use of parenteral nutrition support, a history of underlying diseases such as congenital disorders, immune diseases, renal and hepatic insufficiency, and pancreatitis, a history of sensitivity to herbal remedies such as turmeric and pepper, and regular use of anticoagulant drugs such as warfarin. This study will be performed in the Al-Zahra hospital, an academic hospital affiliated with Isfahan University of Medical Sciences, Isfahan, Iran. INTERVENTION AND COMPARATOR: Sixty eligible patients will be randomly assigned, in a 1:1 ratio, to receive curcumin-piperine capsules (three capsules/day; each capsules containing 500 mg curcumin plus 5 mg piperine; in total 1500 mg curcumin and 15 mg piperine/daily) for seven days (n=30) or matching placebo capsules (three capsules/day; each capsules containing 505 mg maltodextrin; totally 1515 mg, maltodextrin/ daily) for same duration (n=30). Capsules will be administered after oral or enteral feeding at 9, 15 and 21 o'clock. MAIN OUTCOMES: The primary outcome is the time from initiation of supplementation (curcumin-piperine or placebo) to normalization of fever, respiratory rate, and blood oxygen saturation. The secondary outcomes are the mortality rate, length of stay in ICU, temperature, levels of blood oxygen saturation, ventilator dependency, respiratory rate, levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), levels of liver markers (ALT, AST, LDH), and levels of kidney function markers (BUN, Creatinine). FOLLOW UP: All of the parameters will be assessed at baseline and end of the study (7 days intervention). In addition, the rate of mortality will be collected after 4 weeks (28 days' mortality in the ICU, 4 weeks follow up). RANDOMISATION: Eligible patients will be randomly assigned to either the intervention group (Curcumin-piperine) or the control group (Placebo). Randomization sequences will be generated using an electronic table of random numbers to allocate the included participants into either control or intervention groups (in a 1:1 ratio) using the stratified block randomization method. Stratification was conducted according to sex (male and female), with a block size of four. The allocation sequences will be prepared by an independent statistician and will be kept inside sealed, opaque, and consecutively numbered envelopes. Participants, investigators, nurses, and physicians will be unaware of the trial-group assignment. BLINDING (MASKING): This study is a double-blind clinical trial (participants, investigators, nurses, and physicians). The curcumin-piperine and placebo supplements will be similar in the terms of texture, taste, color, odor, and weight. Both tablets will be provided in containers that are completely identical in weight, shape, labeling, and packaging. All participants, investigators, nurses, and physicians will be unaware of the trial-group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is estimated at 60 participants, including 30 patients in the intervention group and 30 patients in the placebo group. TRIAL STATUS: The protocol is Version 2, registered on May 13, 2021. Recruitment began May 20, 2021, and is anticipated to be completed by September 20, 2021. TRIAL REGISTRATION: This trial has been registered in Iranian Registry of Clinical Trials (IRCT) with the title of "Evaluation of the effect of curcumin-piperine supplementation in patients with coronavirus admitted to the intensive care unit (ICU): a double-blind clinical trial study". IRCT registration number is IRCT20121216011763N52 . The registration date was May 13, 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (File 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Curcumin for the Treatment of Prostate Diseases: A Systematic Review of Controlled Clinical Trials.

Prostate cancer is one of the significant causes of morbidity and mortality worldwide. Benign prostatic hyperplasia is another condition of the prostate which, like prostate cancer, is more common among ageing men and is linked to inflammation. In this study, a systematic review was undertaken to estimate the effect of turmeric or curcumin supplementation on prostate diseases. A comprehensive search was conducted in PubMed, Scopus, ISI Web of Science and Google Scholar up to 15 April 2020 to identify clinical trials assessing the effects of curcumin/turmeric alone or in combination with other herbs on prostate diseases. This led to the identification of 11 records comprising 745 patients who met the eligibility criteria. Eight studies were conducted on patients with prostate cancer, and three were on other diseases of the prostate. Although outcomes across the studies were heterogeneous, in some studies curcumin/turmeric supplementation had some favourable effects. This included beneficial effects on the levels of prostate-specific antigen (PSA) (2/6 studies), quality of life (1/2 studies), as well as on oxidative stress markers, feelings of incomplete bladder emptying, urination frequency, intermittency, urgency, weak stream, straining and nocturia. Curcumin/turmeric supplementation had no significant adverse effects among patients. This study demonstrated that turmeric or curcumin supplementation might have beneficial effects on some parameters related to prostate diseases, but it should be noted that some studies showed no effect. Therefore, further studies using curcumin-related compounds, particularly in highly bioavailable forms, are needed to assess the impact of curcumin on prostate conditions.

The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective.

Sepsis and septic shock are still a leading cause of mortality and morbidity in intensive care units worldwide. Sepsis is an uncontrolled and excessive response of the innate immune system toward the invading infectious microbes, characterized by the hyper-production of pro-inflammatory mediators such as interleukin (IL)-1ß, IL-6, tumor-necrosis factor (TNF)-α, and high-mobility group box 1 (HMGB1). In severe sepsis, the overwhelming production of pro-inflammatory cytokines and reactive oxygen species may compromise organ function and lead to the induction of abnormal apoptosis in different organs, resulting in multiple organ dysfunction syndrome and death. Hence, compounds that are able to attenuate inflammatory responses may have therapeutic potential for sepsis treatment. Understanding the pathophysiology and underlying molecular mechanisms of sepsis may provide useful insights in the discovery and development of new effective therapeutics. Therefore, numerous studies have invested much effort into elucidating the mechanisms involved with the onset and development of sepsis. The present review mainly focuses on the molecules and signaling pathways involved in the pathogenicity of sepsis. Additionally, several well-known natural bioactive herbal compounds and phytochemicals, which have shown protective and therapeutic effects with regard to sepsis, as well as their mechanisms of action, are presented. This review suggests that these phytochemicals are able to attenuate the overwhelming inflammatory responses developed during sepsis by modulating different signaling pathways. Moreover, the anti-inflammatory and cytoprotective activities of phytochemicals make them potent compounds to be included as complementary therapeutic agents in the diets of patients suffering from sepsis in an effort to alleviate sepsis and its life-threatening complications, such as multi-organ failure.

Evaluation of the effect of curcumin on pneumonia: A systematic review of preclinical studies.

Pneumonia is a major cause of morbidity and mortality worldwide and causes a significant burden on the healthcare systems. Curcumin is a natural phytochemical with anti-inflammatory and anti-neoplastic characteristics. The aim of this study was to conduct a systematic review of published studies on the effect of curcumin on preclinical models of pneumonia. A comprehensive search was conducted in PubMed/Medline, Scopus, Web of Science and Google Scholar from inception up to March 1, 2020 to recognize experimental or clinical trials assessing the effects of curcumin on pneumonia. We identified 17 primary citations that evaluated the effects of curcumin on pneumonia. Ten (58.8%) studies evaluated the effect of curcumin on mouse models of pneumonia, generated by intranasal inoculation of viruses or bacteria. Seven (41.2%) studies evaluated the inhibitory effects of curcumin on the pneumonia-inducing bacteria. Our results demonstrated that curcumin ameliorated the pneumonia-induced lung injury, mainly through a reduction of the activity and infiltration of neutrophils and the inhibition of inflammatory response in mouse models. Curcumin ameliorates the severity of pneumonia through a reduction in neutrophil infiltration and by amelioration of the exaggerated immune response in preclinical pneumonia models.

Comparing the Efficacy of Two Drugs Senalin and Bisacodyl in Treatment of Constipation in Intensive Care Units' Patients.

BACKGROUND: Constipation is an intestinal syndrome that can be created alone or in the context of another disease in patients admitted to intensive care units (ICUs). Given the role of sennosides in increasing the transfer rate of materials from the large intestine, we aimed to compare the effect of senalin with bisacodyl on the treatment of constipation in patients admitted to ICUs. MATERIALS AND METHODS: In this randomized, double-blind study, 70 patients admitted to the ICU were divided into two groups. The senalin recipient group received senalin with a dose of 500 mg daily for 3 days. The bisacodyl recipient group received bisacodyl with a dose of 10 mg daily for 3 days. RESULTS: The mean of defecation frequency during the 2nd day of treatment of constipation was significantly higher in the group receiving bisacodyl than in the senalin group (P < 0.01). There was no significant difference between the two groups in terms of fecal consistency in any of the study days (P < 0.05). The prevalence of complications in the 3rd day of treatment was significantly higher in bisacodyl group than in the senalin group (P = 0.04). CONCLUSION: Given the lack of difference in the efficacy of two drugs, fecal consistency, daily defecation frequency and fewer complications of senalin compared to bisacodyl, it s eems that this drug can be used as an appropriate treatment for constipation in patients admitted to ICUs.