The efficacy of teriparatide (Cinnopar®) on bone repair in mandibular fractures: A single blinded randomized clinical trial.

This study focused on the effects of teriparatide (CinnoPar) on healing and postoperative complications in mandibular bone fractures. In this single-blind randomized controlled trial, 30 patients with a mandibular fracture hospitalized for open reduction internal fixation were randomly assigned to the intervention (I) (n = 15) and control (C) (n = 15) groups. Both groups received daily acetaminophen and cephalexin for 1 week. For 1 month, Group I received daily subcutaneous teriparatide injections. The Radiographic Union Scale of the Mandible (RUSM) was used to assess mandibular bone fusion subjectively, and the Hounsfield unit (HU) was used to objectively assess radiodensity in a computed tomography (CT) scan. In both groups, the visual analog scale (VAS) score was used to assess postoperative complications such as pain, swelling, wound opening, pus secretion, and bitter taste. There was no significant difference in bone repair between the two groups in this study (P > 0.05). Teriparatide also had no effect on the postoperative complication rate in the control group (P > 0.05). Within the limitations of the study it seems that in mandibular fractures, teriparatide did not affect bone fusion or postoperative complications, so its use is not recommended for better bone fusion and fewer postoperative complications of mandibular fracture during the first month.

Putative Therapeutic Impact of Inflammasome Inhibitors against COVID-19-Induced ARDS.

Given the importance of COVID-19-induced ARDS, recently, researchers have strived to determine underlying mechanisms involved in the inflammatory responses. In this regard, inflammasomes possess a distinct priority for cytokine storm occurrence and subsequently ARDS progression in ill patients with SARS-CoV-2 infection. In this mini-review, the characteristics of known inflammasome inhibitors and designed research in this field were concretely deciphered.

Efficacy and safety of Tocilizumab, plasmapheresis and their combination in severe COVID-19: A randomized clinical trial.

BACKGROUND: This study sought to evaluate and compare the effectiveness of plasmapheresis, Tocilizumab, and Tocilizumab with plasmapheresis treatment on the removal of inflammatory cytokines and improvement clinically of patients with severe COVID-19 in Intensive Care Units (ICU) due to the association between increased cytokine release and the severity of COVID-19. METHODS: This clinical trial study was conducted in three treatment arms in Iran. All patients received standard care and randomization into one of three treatment groups; Tocilizumab (TCZ) alone, plasmapheresis alone, or a combination of Tocilizumab and plasmapheresis. Demographics, clinical evaluation, oxygenation status, laboratory tests and imaging data were evaluated in the three groups and re-checked 48 h after the end of treatment trials. Primary outcomes were oxygenation status, the need for mechanical ventilation and the rate of death. RESULTS: Ninety-four patients were included in the trial after meeting the eligibility requirements. Twenty-eight patients received Tocilizumab alone, 33 had plasmapheresis alone, and 33 received both Tocilizumab and plasmapheresis. Baseline characteristics did not differ between three groups that included demographic, clinical and laboratory parameters. Following therapy, there was no difference between the three groups for CRP, ferritin, d-dimer, IL-6, pro-calcitonin and neutrophil to lymphocyte ratio (NLR) (P > 0.05). While a significant reduction was found in CRP levels within each group (32.04 ± 42.43 to 17.40 ± 38.11, 51.28 ± 40.96 to 26.36 ± 33.07 and 41.20 ± 34.27 to 21.56 ± 24.96 in the tocilizumab, plasmapheresis, and combined group, respectively) (p < 0.05), procalcitonin levels were elevated significantly in the Tocilizumab group (0.28 ± 0.09 to 0.37 ± 0.11) (p < 0.05). Clinically there was no difference between the three groups following treatment for O2 saturation levels with supplementary oxygen at discharge, endotracheal intubation rate, use of NIVPP, mortality, mean hospital and ICU length of stay (p > 0.05). CONCLUSION: Study results showed that the reduction of serum inflammatory markers, the rate of intubation and therapeutic complications including death were no different between the three groups; however, CRP levels were significantly reduced in all three groups, indicating that the interventions reduced inflammation likely through a reduction in the cytokine storm, though clinical outcomes were unaffected.

Pharmacological treatments of COVID-19.

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and sub-clinical studies are currently undertaken to find a gold-standard therapeutic regimen with high efficacy and low side effect. Based on the published scientific evidence published to date, we summarized herein the effects of different potential therapies and up-to-date clinical trials. The review is intended to help readers aware of potentially effective COVID-19 treatment and provide useful references for future studies.

Pharmacotherapy consideration of thrombolytic medications in COVID-19-associated ARDS.

BACKGROUND: In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for coronavirus disease (COVID-19), was identified as the new pathogen to lead pneumonia in Wuhan, China, which has spread all over the world and developed into a pandemic. Despite the over 1 year of pandemic, due to the lack of an effective treatment plan, the morbidity and mortality of COVID-19 remains high. Efforts are underway to find the optimal management for this viral disease. MAIN BODY: SARS-CoV-2 could simultaneously affect multiple organs with variable degrees of severity, from mild to critical disease. Overproduction of pro-inflammatory mediators, exacerbated cellular and humoral immune responses, and coagulopathy such as Pulmonary Intravascular Coagulopathy (PIC) contributes to cell injuries. Considering the pathophysiology of the disease and multiple microthrombi developments in COVID-19, thrombolytic medications seem to play a role in the management of the disease. Beyond the anticoagulation, the exact role of thrombolytic medications in the management of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) is not explicit. This review focuses on current progress in underlying mechanisms of COVID-19-associated pulmonary intravascular coagulopathy, the historical use of thrombolytic drugs in the management of ARDS, and pharmacotherapy considerations of thrombolytic therapy, their possible benefits, and pitfalls in COVID-19-associated ARDS. CONCLUSIONS: Inhaled or intravenous administration of thrombolytics appears to be a salvage therapy for severe ARDS associated with COVID-19 by prompt attenuation of lung injury. Considering the pathogenesis of COVID-19-related ARDS and mechanism of action of thrombolytic agents, thrombolytics appear attractive options in stable patients without contraindications.

COVID-19-infected woman along with tuberculosis and psychogenic non-epileptic seizures: A case report.

During the COVID-19 pandemic, we should not forget about chronic, underlying and important diseases, especially diseases that cause immune system deficiency, of which TB is one and may be missed. Also, we should pay attention to the past medical history of the patients and their drug-drug interactions during the treatment period of COVID-19. Our main clinical message is that diseases such as TB, which weaken the immune system, may predispose a person to COVID-19 infection and COVID-19 may exacerbate TB and it's mortality. On the other hand, diseases that target the lung tissue such as TB and COVID-19, may have synergistic effects and increase mortality (for a patient whose lung capacity is reduced due to TB, superimposed COVID-19 can worsen the situation). In addition, it may be necessary to take more serious considerations for COVID-19 in low socio-economy countries, such as Afghanistan, where TB is more prevalent.

Efficacy and safety of Levamisole treatment in clinical presentations of non-hospitalized patients with COVID-19: a double-blind, randomized, controlled trial.

BACKGROUND: Levamisole has shown clinical benefits in the management of COVID-19 via its immunomodulatory effect. However, the exact role of Levamisole effect in clinical status of COVID-19 patients is unknown. We aimed to evaluate the efficacy of Levamisole on clinical status of patients with COVID-19 during their course of the disease. METHODS: This prospective, double-blind, randomized controlled clinical trial was performed in adult patients with mild to moderate COVID-19 (room-air oxygen saturation > 94%) from late April 2020 to mid-August 2020. Patients were randomly assigned to receive a 3-day course of Levamisole or placebo in combination with routine standard of care. RESULTS: With 25 patients in each arm, 50 patients with COVID-19 were enrolled in the study. Most of the study participants were men (60%). On days 3 and 14, patients in Levamisole group had significantly better cough status distribution when compared to the placebo group (P-value = 0.034 and 0.005, respectively). Moreover, there was significant differences between the two groups in dyspnea at follow-up intervals of 7 (P-value = 0.015) and 14 (P-value = 0.010) days after receiving the interventions. However, no significant difference in fever status was observed on days 1, 3, 7, and 14 in both groups (P-value > 0.05). CONCLUSION: The results of the current study suggest that Levamisole may improve most of clinical status of patients with COVID-19. The patients receiving Levamisole had significantly better chance of clinical status including cough and dyspnea on day 14 when compared to the placebo. However, the effect-size of this finding has uncertain clinical importance. TRIAL REGISTRATION: The trial was registered as IRCT20190810044500N7 (19/09/2020).

The prophylaxis and treatment potential of supplements for COVID-19.

The global impact of the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infection that caused COVID-19 has been evident in the last few months from the unprecedented socioeconomic disruption to more than 600,000 deaths. The lack of vaccine and effective therapeutic agents for the disease prompted world-wide effort to test those antiviral therapeutics already in use for other diseases. Another interesting approach has been based on the pathological sequel of the disease that involve severe inflammatory reaction (or the cytokine storm) associated with pneumonia in critically ill patients. This article outlines the prophylaxis therapeutic potential of supplements vitamins and micronutrients in COVID-19. By ameliorating the inflammatory and oxidative stress associated with the disease and some direct antiviral effects, the application of these agents as adjuvants and other alternative approaches are discussed. Available clinical trials including those currently registered on these supplements are scrutinized.

Neutrophil elastase inhibitor (sivelestat) may be a promising therapeutic option for management of acute lung injury/acute respiratory distress syndrome or disseminated intravascular coagulation in COVID-19.

WHAT IS KNOWN AND OBJECTIVE: This article summarizes the effects of sivelestat on acute lung injury/acute respiratory distress syndrome (ALI/ARDS) or ARDS with coagulopathy, both of which are frequently seen in patients with COVID-19. COMMENT: COVID-19 patients are more susceptible to thromboembolic events, including disseminated intravascular coagulation (DIC). Various studies have emphasized the role of neutrophil elastase (NE) in the development of DIC in patients with ARDS and sepsis. It has been shown that NE inhibition by sivelestat mitigates ALI through amelioration of injuries in alveolar epithelium and vascular endothelium, as well as reversing the neutrophil-mediated increased vascular permeability. WHAT IS NEW AND CONCLUSIONS: Sivelestat, a selective NE inhibitor, has not been evaluated for its possible therapeutic effects against SARS-CoV-2 infection. Based on its promising beneficial effects in underlying complications of COVID-19, sivelestat could be considered as a promising modality for better management of COVID-19-induced ALI/ARDS or coagulopathy.