Venipuncture is a common and painful procedure in neonates. Sweet solutions (sucrose and glucose) are recommended and widely used as standard care for reducing neonatal procedural pain. Topical local anesthetics may also reduce procedural pain but generally require longer application times to achieve adequate analgesia. This study investigated the efficacy and safety of a novel topical lidocaine–nitroglycerin preparation as an adjunct to standard oral sweet solutions in neonates undergoing peripheral venous catheterization. In this double-blind randomized clinical trial, 84 neonates (≥ 34 weeks gestation) undergoing peripheral venous catheterization were randomized to receive either topical lidocaine/nitroglycerin 2 https://irct.behdasht.gov.ir/trial/47524 .

Background: Timolol is a beta-adrenergic blocker that has been shown to be effective in the healing of wounds. Oral mucositis (OM), an acute inflammation of the oral mucosa, is a bothersome side effect of some regimens of chemotherapy in which the oral mucosa becomes ulcerated. The current study aimed to evaluate the prophylactic effects of timolol mouthwash in preventing OM in adult patients receiving chemotherapy compared to the placebo Method: This randomized, double-blind trial was conducted on 30 adult patients receiving chemotherapy regimen, including doxorubicin or 5-fluorouracil (5-FU). The patients were randomized in a 1:1 ratio to receive either timolol 0.5% (w/v) (n = 15) or placebo (n = 15) mouthwash 5 ml three times per day. The outcomes of the study were the intensity of OM evaluated by the World Health Organization (WHO) mucositis scale and OM-related pain based on the Visual Analog Scale (VAS) weekly during the seven weeks of the study period. Results: The results of the study showed that the scores of WHO mucositis scale significantly decreased in the timolol group compared to the control group during the study [week 1: mean (SD), 0.02 (0.41) in the timolol group, and 0.67 (0.48) in the control group; week 7: mean (SD), 0.33 (0.61) in the timolol group, and 0.87 (0.74) in the control group; P-value = 0.049]. Moreover, the mean pain scores significantly decreased in the first, second, and third weeks in the timolol group compared to the control group (P-value < 0.05). Conclusion: The results of this preliminary clinical trial demonstrated that among the patients receiving doxorubicin or 5-FU chemotherapy regimens, the preventive use of timolol mouthwash significantly diminished the severity of OM compared to the control group during the seven weeks of follow-up. The severity of pain was also significantly lower during the first three weeks of the study; however, the effect size was less than the minimal clinically important difference. Further studies are required to assess both the long-term efficacy and safety of timolol mouthwash in preventing OM.

Background: COVID-19 is characterized by immune dysregulation, endothelial dysfunction, and thrombo-inflammation. Pentoxifylline (PTX) has been proposed as an adjunctive modality for COVID-19. Regarding the inconsistent results of earlier trials, this systematic review was conducted to evaluate the efficacy of PTX in COVID-19 patients. Methods: For the study literature up to 16 September 2025 was systematically searched for randomized controlled trials evaluating pentoxifylline in COVID-19. Continuous outcomes were expressed as Mean Differences (MDs) or Standardized Mean Differences (SMDs), whereas dichotomous outcomes were expressed as Odds Ratios (ORs) with 95% confidence intervals. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Results: Seven randomized trials (551 participants) were included. Pentoxifylline significantly improved oxygen saturation (SMD = 0.215; 95% CI: 0.016 to 0.415; P = 0.034) and was associated with reduced ICU admission (OR = 0.454; 95% CI: 0.224 to 0.917; P = 0.028). It also significantly reduced inflammatory markers, including CRP and ESR. Effects on mortality, mechanical ventilation requirement, and hospital length of stay were not statistically significant. Risk-of-bias assessments indicated generally low methodological concerns, with minor issues related to blinding. Publication bias could not be reliably assessed for several outcomes because of the small number of included studies. Conclusion: The results of the present study suggest that pentoxifylline may reduce systemic inflammation and improve oxygenation in hospitalized adults with COVID-19. It may also be associated with reduced ICU admission; however, its effects on mortality, mechanical ventilation requirement, and hospital length of stay remain uncertain. Larger, rigorously designed randomized trials are needed to confirm these findings.

: Diabetic neuropathy is a prevalent and debilitating complication of type 2 diabetes, resulting in functional impairments. Crocin, a bioactive constituent of saffron (Crocus sativus), has long been utilized in traditional medicine for its potential therapeutic effects. This study aimed to evaluate the efficacy of Crocin in alleviating neuropathic symptoms in patients with type 2 diabetes. In this triple-blind, randomized, placebo-controlled clinical trial, patients with type 2 diabetes and confirmed peripheral neuropathy were randomly assigned to receive either 15 mg/day of Crocin or a matching placebo for 12 weeks. Neuropathic symptoms were assessed using the Total Symptom Score (TSS), Visual Analog Scale (VAS), and the Michigan Neuropathy Screening Instrument (MNSI) at baseline and at 3-week intervals. Forty-two patients completed the study, with 21 participants in each group. By week 9, the Crocin group exhibited a significantly lower mean TSS (5.1 ± 1.39) compared to the placebo group (6.6 ± 1.00, P = 0.005). Similarly, VAS scores, reflecting pain intensity, were significantly reduced in the Crocin group at both weeks 6 and 9 (P = 0.019). MNSI scores at week 9 also favored the Crocin group (5.7 ± 1.1 vs. 6.8 ± 0.9, P = 0.03). Crocin may offer promising therapeutic benefits in reducing pain and neuropathic symptoms in patients with type 2 diabetes. Its neuroprotective, antioxidant, and antihyperglycemic properties may contribute to these effects. While the findings support the potential beneficial effect of crocin in the management of diabetic neuropathy, further large-scale and more robust clinical trials are warranted to validate these results. https//irct.ir/ IRCT20190810044500N8, Registration date 01/01/2021.

Background: Coronary Artery Bypass Graft (CABG) surgery is employed to increase the lifespan of patients with Coronary Artery Disease (CAD). The low serum levels of essential elements have a negative effect on patients undergoing CABG. Objective: This clinical trial aimed to investigate the effect of trace elements supplements on postoperative outcomes after coronary artery bypass graft. Methods: Two hundred patients underwent on-pump CABG to randomly receive either Addamel©, which contains essential trace elements, or isotonic saline for 3 days. We measured postoperative plasma Zn, Se, Cu, Mn, Se, and Fe concentrations, and the levels of highly sensitive C-reactive Protein (hs-CRP) on days 0, 1, and 2. Duration of hospital and Intensive Care Unit (ICU) stay, 30-day mortality, and the incidence of Arterial Fibrillation (AF) have been evaluated as secondary outcomes. Results: In the supplemented group, the plasma levels of Cu and Mn increased by day 3, and plasma hs-CRP increased by day 1 in both groups, but it decreased in patients who received trace elements supplementation on day 2. The Addamel group had a lower mortality rate, though the difference did not reach a significant level. There was a significant negative correlation observed between plasma Zn level and 30-day mortality, along with another significant negative link between plasma CRP level before operation and Sepsis-related Organ Failure Assessment (SOFA) score. Other measured parameters were similar between the intervention and placebo groups. Conclusion: The patients undergoing CABG appeared to benefit from trace element supplementation. A brief period of Addamel administration following CABG could prevent a decrease in the serum concentration of trace elements and reduce the circulating plasma CRP

Introduction and objectives This research aims to examine the efficacy of melatonin as an adjuvant therapeutic agent for COVID-19 patients in the intensive care unit. Methods A randomized, double-blind, placebo-controlled investigation was conducted on a group of hospitalized COVID-19 patients. Individuals were allocated into 2 groups: one group received a combination of 18 mg of melatonin and standard treatment for 14 days; the other group received a placebo in addition to standard treatment. Patients were evaluated at the beginning of the study as well as the 7th and 15th days to analyze changes in clinical symptoms, P/F ratio, and inflammatory markers. Results The study included patients with an average age of 57.80±17.96 years, with an equal gender representation. The average length of hospital stay was 19.83±4.45 days. Hypertension and diabetes were commonly observed comorbidities. There were no significant differences in the demographic characteristics between the 2 groups (P>.05). Additionally, there were no significant distinctions between the 2 groups in terms of clinical symptom improvement, mortality rate, adverse effects, and various blood markers (P>.05). Conclusion Our study's findings suggested that melatonin is unlikely to significantly affect the clinical status of COVID-19 patients.

BACKGROUND:Despite extensive efforts to improve survival in cardiac arrest (CA), the optimal pharmacologic strategy during resuscitation remains uncertain. While prior meta-analyses have explored individual drug classes, the relative effectiveness of combined regimens remains inadequately defined. This network meta-analysis (NMA) aims to evaluate and compare the efficacy of triple therapy with vasopressin (VP), steroids, and epinephrine (EP) in CA patients. METHODS:A comprehensive electronic search was conducted in PubMed, Scopus, ISI Web of Science, the Cochrane Central Register of Controlled Trials, Google Scholar, and other bibliographic databases. Randomized clinical trials (RCTs) evaluating the use of steroids, epinephrine, and vasopressin in CA patients were included. In trials that involved additional agents (e.g., lidocaine), only the data pertaining to epinephrine/vasopressor-based interventions were extracted and synthesized to ensure comparability with the study scope. Out of 3453 identified studies, 36 RCTs involving 21,768 patients were included. Interventions during cardiopulmonary resuscitation were categorized as monotherapy, double therapy, or triple therapy (VSE). Primary outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, 24-h survival, and survival to hospital discharge. Neurological outcomes were also evaluated to determine functional recovery, when consistently reported, although heterogeneity of measurement tools precluded quantitative synthesis. RESULTS:Triple therapy (VSE) and the combination of epinephrine plus steroids demonstrated the highest probability of improving all major survival outcomes. Ranking analysis consistently favored VSE over monotherapies to improve clinical outcomes of CA patients. CONCLUSION:This NMA provides comparative evidence supporting the superiority of epinephrine-steroid double therapy and VSE triple therapy in improving resuscitation outcomes in cardiac arrest. These findings may inform future guidelines and clinical decision-making. PROSPERO REGISTRATION:CRD42022296508.

Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in women of reproductive age. Crocin is known as the main component of saffron, which has antioxidant properties and has the ability to scavenge free radicals. Considering the pathophysiology of PCOS and also the anti-inflammatory and antioxidant properties of crocin in improving insulin resistance, we aimed to evaluate the efficacy of the combination of crocin and metformin compared to metformin alone in PCOS patients. This study is a prospective, double-blind randomized controlled clinical trial. Fifty patients with PCOS and hirsutism were included from Baqaipour Obstetrics and Gynecology Clinic in Yazd and randomly assigned into the two study arms of control group [metformin and placebo (n = 25)] or intervention group [metformin and crocin (n = 25)]. Patients were administered crocin 15 mg tablets once a day in combination with metformin 500 mg twice a day for 12 weeks to complete three full periods of the monthly cycle. The studied endpoints were evaluated at the beginning and end of the study. Crocin significantly improved the serum level of follicle-stimulating hormone (FSH) (P = 0.048) and Ferriman- Gallwey score (P = 0.042) at day 90. Furthermore, crocin group had a significant improvement in terms of acne severity at the end of the study (P = 0.03), so that none of the patients in the crocin group had severe acne at the end of the study. However, the comparisons between two groups were not statistically significant for other evaluated outcomes including fasting blood sugar (FBS), dihydroepiandrosterone-sulfate (DHEA-S), luteinizing hormone (LH), dermatology life quality index (DLQI), and blood pressure (BP) at the end of the study. In the present study, concurrent use of crocin along with metformin was significantly effective in ameliorating the unpleasant side effects of PCOS, including hirsutism and acne, and increasing FSH sex hormone levels in patients with PCOS. 26/08/2021, Trial Registry number: IRCT20210730052027N1.

Mechanical ventilation (MV) is a cornerstone of supportive care in intensive care units (ICUs), but prolonged ventilation is associated with adverse outcomes. Several pharmacologic agents with respiratory stimulants have been investigated to facilitate weaning and improve clinical outcomes; yet no comprehensive comparison across available agents exists. This network meta-analysis (NMA) aimed to compare and rank available interventions in adult patients receiving MV. A systematic search of PubMed, Web of Science, and Scopus (up to November 10, 2023) identified 15 randomized controlled trials (1,528 participants) evaluating ten respiratory stimulants in mechanically ventilated critically ill adults: Almitrine Bismesylate (AB), Doxofylline (DX), Progesterone (PRG), Acetazolamide (ACZT), Growth Hormone (GH), Oxandrolone (OXA), Nandrolone (NA), Caffeine (CAF), Donepezil (DPZ), and a multi-agent adjuvant therapeutic (AT) regimen containing anisodamine. Data were analyzed using a frequentist network meta-analysis with treatment rankings based on SUCRA values. Risk of bias was assessed using the modified Cochrane RoB 2 tool. No pharmacologic intervention significantly reduced hospital or ICU mortality, duration of mechanical ventilation, or time to successful weaning compared with placebo. According to SUCRA rankings, NA, OXA, and PRG had the highest probabilities of reducing hospital mortality, with NA also associated with shorter ICU and hospital stays. DPZ and PRG significantly shortened weaning duration, while GH showed the greatest reduction in mechanical ventilation duration. GH, PRG, and DPZ had the highest likelihood of successful weaning. Heterogeneity and inconsistency were generally low, except for the duration of mechanical ventilation (I² = 86.2%, p < 0.001). No pharmacologic intervention significantly reduced hospital mortality. However, agents such as NA, GH, and DPZ may help shorten ICU stay, reduce duration of mechanical ventilation, or improve weaning efficiency. These findings underscore the potential value of multi-agent adjuvant approaches and highlight the need for larger, high-quality trials to confirm their clinical benefits.Trial registration: CRD42023454122 (18/10/2023).

Premenstrual syndrome (PMS) is a prevalent and often debilitating health conditions affecting women of reproductive age. The natural PMSoff supplement contains several active ingredients, including spirulina, whey protein, calcium citrate, vitamin B1, chamomile, turmeric, marigold, lavender, saffron, valerian, and aftimoon. This clinical trial aimed to assess the efficacy and safety of PMSoff, a natural supplement, in alleviating the symptoms of PMS. In this double-blind, randomized trial, women diagnosed with PMS were randomly assigned to receive either PMSoff or placebo. The primary objective of the study was to evaluate the impact of PMSoff on symptom severity, with secondary objectives focusing on safety and adherence. The primary outcome of this study was the severity of PMS symptoms, evaluated using the Daily Record of Severity of Problems (DRSP) questionnaire. The secondary outcome focused on the presence of premenstrual dysphoric disorder (PMDD), a more severe and debilitating form of PMS. Symptom severity was assessed at multiple time points: pre-intervention, one month post-intervention, and two months post-intervention. Of the 255 randomized participants, 218 (85.4

Osteoarthritis (OA) is a common musculoskeletal disorder characterized by joint degeneration. OA involves not only cartilage but also other joint components such as subchondral bone and synovium. OA is potentially linked to systemic inflammation. Non-pharmacological strategies are foundational in the management of OA, while medications such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are also commonly prescribed. Notably, oral NSAIDs pose significant gastrointestinal adverse effects, while topically applied NSAIDs are less likely to result in side effects. Meloxicam, a selective NSAID, has shown promise in the management of osteoarthritis with its analgesic and anti-inflammatory properties, particularly in topical formulations. While osteoarthritis lacks a definitive cure, proactive medical management can mitigate further joint damage and potentially promote tissue restoration and offer hope for improved outcomes in affected individuals. This clinical trial was conducted to evaluate the efficacy of topical meloxicam 1 https://irct.ir/IRCT20190810044500N15 (May 05, 2021).

BACKGROUND AND OBJECTIVE:Recurrent uncomplicated cystitis is highly prevalent among women. Antioxidants are often used as adjunctive therapy in urinary tract infections (UTIs) to counteract oxidative stress and restore a healthy urinary environment. This study aimed to evaluate the effect of vitamin E on the treatment and prevention of recurrent lower UTIs in women. MATERIALS AND METHODS:This clinical trial included 88 female patients over 18 years old with lower UTI who were referred to the infectious diseases clinic at Vali-Asr Hospital in Birjand. Patients were initially assessed 3-5 days after starting antibiotics, and then at 3 and 6 month intervals for urinary symptoms and UTI recurrence. Patients were randomly assigned into one of the following groups: control group receiving antibiotics and a placebo, and the intervention group receiving antibiotics along with 100 IU of vitamin E daily. After completing a 3-day course of cefixime (400 mg/day), the intervention group continued vitamin E supplementation for six months. Data analysis was performed using SPSS version 19, with statistical significance set at P < 0.05. RESULTS:The mean age of the patients was 45.48 ± 14.23 years. After 3 days, the intervention group showed a significant improvement in urinary frequency and dysuria compared to the control group (P < 0.05), while improvement in urgency did not significantly differ between groups (P = 0.43). At 3 and 6 month intervals, UTI recurrence was significantly lower in the intervention group (P < 0.001; effect size = 0.52 and 0.69, respectively). Additionally, the average duration of recovery was significantly faster in the intervention group compared to the control group (P = 0.002). CONCLUSION:Supplementing women with lower UTI with 100 IU of vitamin E daily to the antibiotic regimen significantly reduces recovery time, improves urinary symptoms (frequency and dysuria), and lowers UTI recurrence rates. However, further randomized clinical trials with large sample size are recommended to confirm these findings. TRIAL REGISTRATION:Iranian Registry of Clinical Trials Identifier: IRCT20210617051604N1 (July 11, 2021).

In acute exacerbation periods of chronic obstructive pulmonary disease (COPD), patients may experience hypoxemia or hypercapnia. Noninvasive ventilation (NIV) and respiratory stimulant drugs are used to treat this condition. Medroxyprogesterone acetate (MPA) can cross the blood-brain barrier and cause breathing stimulation and hyperventilation. This study was conducted to investigate the effectiveness of MPA in hypercapnic exacerbated COPD patients and the possibility of faster weaning of patients from NIV. This double-blind clinical trial was conducted on consecutive exacerbated COD patients referred to Shahid Rahnemoun Hospital, Yazd, Iran, from February 2022 to August 2022. Through a block randomized sampling method with a 1:1 allocation ratio, 58 eligible patients with hypercapnic exacerbated COPD on NIV were divided into two study groups: the intervention (treated with MPA 10 mg every 8 h) and the control (treated with placebo). The clinical and arterial blood gas (ABG) parameters were investigated in both groups. Out of 50 patients, 27 and 23 intervention and control arms cases were analyzed. Although there was a significant difference in the amount of ABG parameters during the study in each group, there was no statistically significant difference between the two groups. Also, There was no significant difference in the total weaning rate of the patients in the two groups. Despite the higher number of early weaning in the MPA group, no significant difference was reported between the two groups in this regard. In addition, there was no difference between the two groups in the rate of ICU hospitalization, the length of stay of hospitalization and ICU, and the mortality rate. The administration of MPA has not improved clinical and laboratory results, and MPA is not superior to placebo in the weaning process of patients undergoing NIV. IRCT20190810044500N21 (01/02/2022), (https//irct.behdasht.gov.ir/user/trial/59402/view)

As a major component of innate immunity and a positive regulator of interferons, the Stimulator of interferon gene (STING) has an immunotherapy potential to govern a variety of infectious diseases. Despite the recent advances regarding vaccines against COVID-19, nontoxic novel adjuvants with the potential to enhance vaccine efficacy are urgently desired. In this connection, it has been well-documented that STING agonists are applied to combat COVID-19. This approach is of major significance for boosting immune responses most likely through an autophagy-dependent manner in susceptible individuals against infection induced by severe acute respiratory syndrome Coronavirus (SARS‑CoV‑2). Given that STING agonists exert substantial immunomodulatory impacts under a wide array of pathologic conditions, these agents could be considered novel adjuvants for enhancing immunogenicity against the SARS-related coronavirus. Here, we intend to discuss the recent advances in STING agonists’ recruitment to boost innate immune responses upon vaccination against SARS-related coronavirus infections. In light of the primordial role of autophagy modulation, the potential of being an antiviral vaccine adjuvant was also explored.

BACKGROUND:Burn injuries can cause significant mortality and morbidity. This study aimed to evaluate the efficiency of topical recombinant human erythropoietin (rhEPO) on enhancing burn wound healing. METHODS:In this randomized double-blind controlled clinical trial, we enrolled 40 participants aged 18 years and older who were referred to a burn center during the first 24 h of burning. The participants with no concurrent comorbidities had superficial and deep second-degree burns, no respiratory burns, no face and perineum burns, no keloid formation, or a healed, fully epithelialized, hypertrophic burn scar. Topical rhEPO or nitrofurazone/Vitamin A was administered every other day, and the patients were scheduled for follow-up visits to receive wound cleansing, debridement, and dressing changes. Burn wound healing response to treatment was measured as the study main outcome. RESULTS:At the second follow-up visit, all parameters were significantly lower in the rhEPO group compared with the control group except for itchiness. The results of the next two follow-up sessions were also the same. The total value of the modified Vancouver Scar Scale (VSS) at days 5, 7, and 14 was significantly lower in the rhEPO group compared with the routine of care group. Trial Registry Date: 2022-03-02, Trial Registry number: IRCT20190810044500N23 CONCLUSIONS: The results of the present study suggested that topical rhEPO is a potential option in burn wounds and patient satisfaction, without causing intolerable side effects.

Background: Considering the pathogenesis of psoriasis and also the anti-oxidant, immunomodulatory, and anti-inflammatory properties of rosuvastatin and melatonin, the current clinical trial aimed to evaluate the efficacy of topical rosuvastatin and melatonin in patients with mild to moderate psoriasis. Methods: The current randomized placebo-controlled clinical trial was conducted using a 3-arm parallel group included 77 adult patients (>= 18 years old) with mild to moderate plaque psoriasis. Patients were randomized into a 1:1:1 ratio to one of three groups to receive one of the three interventions: melatonin cream, 5.0% (w/w), rosuvastatin cream, 5.0% (w/w), or placebo cream with a similar transparent appearance twice a day for 12 weeks. The primary outcome was severity of the disease using Psoriasis Area Severity Index (PASI). The secondary outcomes included the Dermatological Sum Score (DSS) to assess the erythema, scaling, and plaque elevation and the Dermatology Life Quality Index (DLQI). Photographs of the lesions were also taken at the baseline and at different periodic intervals thereafter. Results: Among 77 randomized patients, 52 (mean (SD) age, 40.67 (10.85) years; 22 (42.30%) men) completed the study. A significant reduction of 45% (mean (SD) of 2.67 (0.98) to 1.74 (1.12)) and 70% (mean (SD) of 2.67 (0.98) to 1.31 (1.13)) in PASI score, and 46% (mean (SD) of 2.91(1.85) to 1.57 (1.11)) and 77% (mean (SD) of 2.91 (1.85) to 0.87 (0.67)) in DSS score on days 30 and 60 with rosuvastatin cream, 5% w/w (P < 0.001) compared with baseline was observed, respectively. Also a significant decrease of 35% (mean (SD) of 2.67 (0.98) to 1.74 (1.12)) and 51% (mean (SD) of 2.67 (0.98) to 1.31 (1.13)) in PASI score, and 40% (mean (SD) of 5.00 (1.58) to 3.00 (1.76))and 61% (mean (SD) of 5.00 (1.58) to 1.92 (1.71)) in DSS score on days 30 and 60 with melatonin cream, 5% w/w (P < 0.001) compared with baseline were observed, respectively. In each of the melatonin or rosuvastatin groups, DLQI improved significantly on days 30 (P < 0.0001) and 60 (P < 0.001) while the changes in the control group were not significant. Conclusion: The results of this clinical trial demonstrated that topical melatonin and rosuvastatin diminished the severity of mild to moderate plaque psoriasis with a satisfactory safety profile. Future clinical trials should assess both the long-term efficacy and safety of melatonin and rosuvastatin creams in larger study populations.

OBJECTIVE:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a violent attack on the body that leads to multi-organ failure and death in COVID-19 patients. The aim of this study was to systematically review the existing literature on the potential benefits of calcineurin inhibitors (CIs) as anti-vascular endothelial growth factor (VEGF) agents in improving the clinical outcomes of COVID-19 patients. METHODS:We searched various databases, including PubMed, Scopus, ISI Web of Science, Google Scholar, Cochrane databases, and ClinicalTrials.gov from 31st December, 2019, to 3rd February, 2023, for relevant controlled trials. The quality of the evidence was assessed using the Cochrane Collaboration tool. Comprehensive Meta-Analysis Software was used for the statistical analyses using a random-effects model. RESULTS:Three trials enrolling 293 participants were reviewed in the present systematic review and meta-analysis. The results showed CIs to lead to a significant reduction in mortality rate [risk ratio (RR): 0.598, 95% CI: 0.404-0.885, P-value = 0.010] with a low between-study heterogeneity (Cochrane Q test: I2 = 0.000%, P-value = 0.371). Pooled analysis of two studies (84 patients) illustrated that CIs could not significantly increase the rate of hospital discharge (RR: 1.161, 95% CI: 0.764-1.764, P-value = 0.485) and heterogeneity was not significant (Cochrane Q test: I2 = 26.798%, P-value = 0.242). CONCLUSION:CIs are able to inhibit the virus nucleocapsid protein so that they can prevent replication and respiratory tract tissue damage caused by SARS-CoV-2. Based on the characteristics mentioned in detail, CIs can play a potential therapeutic role for COVID-19 patients.

Background: The coronavirus disease of 2019 (COVID-19) may be considered sepsis on the basis that all the pathological events and the subsequent organ-to-organ interaction in sepsis also occur in COVID-19. In this article, the authors first discussed the rationale for the use of vitamin C (Vit-C) in sepsis and septic patients. They also reviewed the role of a high dose of Vit-C in COVID-19, which included clinical trials designed for the management of this viral disease. Methods: The researchers explored databases of PubMed, Scopus, ISI Web of Science, and Google Scholar. Data were extracted to assess the effects of Vit-C in septic patients and also the efficacy of supplementation with a high dose of Vit-C regarding the clinical outcomes of patients with COVID-19. Results: Recent research findings indicate that severe inflammatory responses (cytokine storms) and oxidative stress are important causes for the high mortality in COVID-19 patients. It seems, however, that administering high doses of Vit-C can offer a therapeutic benefit. High doses of intravenous Vit-C, with its antioxidant properties and pleiotropic functions, could attenuate the tissue damage caused by excessive levels of free radicals following the cytokine storm and septic shock in severe cases of the disease. Conclusions: Recent literature suggests that high doses of Vit-C have a potential role in reducing mortality and intubation rates in critically ill COVID-19 patients. However, determining the optimal duration and dose of Vit-C in these patients requires further studies.

Background: This systematic review and meta-analysis aimed to determine whether the combination of hydrocortisone, vitamin C (ascorbic acid), and thiamine (HAT therapy) diminishes the mortality and is effective in expediting the resolution of sepsis and septic shock or not. Methods: The following databases of PubMed, Scopus, ISI Web of Science, and Google Scholar were explored until March 2021 for all existing literature related to this field. An automatic alert for all databases was also activated to update our search. Meta-analysis was performed on clinical trials and cohorts separately as well as on all the pooled populations. Results: This study evaluated nine clinical trials (1358 participants) and nine cohorts (339,437 participants) and is the most comprehensive systematic review in this field. The results of our meta-analysis demonstrated a significant difference in the reduction of Sepsis-Related Organ Failure Assessment (SOFA) score changes (Δ-SOFA) over 72 h (Standard Mean Difference (SMD) = −0.429; 95% CI: −0.737, 0.120; P = 0.006), duration of vasopressor (VP) (SMD = −0.373; 95% CI: −0.619, −0.128; P = 0.003), and procalcitonin (PCT) clearance (SMD = 0.496; 95% CI: 0.061, 0.931%; P = 0.026). Considering the results of cohorts, HAT therapy was effective in the survival of intensive care units (ICUs) patients (OR = 0.641; 95% CI: 0.423-0.970, P = 0.035). However, no significant difference was observed between the intervention and control groups in hospital mortality (Odds Ratio (OR) = 0.811, 95% CI: 0.544-1.209, P = 0.304), 28- to 30-day mortality (OR = 1.000; 95% CI: 0.782-1.279, P = 0.998), new onset acute kidney injury requiring renal replacement therapy ((OR = 0.856, 95% CI: 0.526, 1.391; P = 0.529), in-hospital length of stay (LOS) (SMD = 0.090; 95% CI: −0.036, 0.216 days; P = 0.162), LOS in ICU (SMD = 0.016, 95% CI: −0.138, 0.170 days; P = 0.838), and mechanical ventilation-free days (SMD = 0.004; 95% CI: −0.154, 0.163 days; P = 0.956). Conclusion: Supplementation of septic and septic shock patients with HAT therapy has significant beneficial effects on SOFA score over 72 hours, duration of exogenous vasopressor infusion and procalcitonin clearance. Considering the results of cohort studies, supplementation with HAT is efficacious in reducing ICU mortality.