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Chronic pain is a debilitating symptom with a significant negative impact on the quality of life and socioeconomic status, particularly among adults and the elderly. Major Depressive Disorder (MDD) stands out as one of the most important comorbid disorders accompanying chronic pain. The kynurenine pathway serves as the primary route for tryptophan degradation and holds critical significance in various biological processes, including the regulation of neurotransmitters, immune responses, cancer development, metabolism, and inflammation. This review encompasses key research studies related to the kynurenine pathway in the context of headache, neuropathic pain, gastrointestinal disorders, fibromyalgia, chronic fatigue syndrome, and MDD. Various metabolites produced in the kynurenine pathway, such as kynurenic acid and quinolinic acid, exhibit neuroprotective and neurotoxic effects, respectively. Recent studies have highlighted the significant involvement of kynurenine and its metabolites in the pathophysiology of pain. Moreover, pharmacological interventions targeting the regulation of the kynurenine pathway have shown therapeutic promise in pain management. Understanding the underlying mechanisms of this pathway presents an opportunity for developing personalized, innovative, and non-opioid approaches to pain treatment. Therefore, this narrative review explores the role of the kynurenine pathway in various chronic pain disorders and its association with depression and chronic pain.
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Chronic Pain , Kynurenine , Kynurenine/metabolism , Humans , Chronic Pain/metabolism , Animals , Signal TransductionABSTRACT
Introduction: Infectious diarrhea, a significant global health challenge, is exacerbated by flooding, a consequence of climate change and environmental disruption. This comprehensive study aims to quantify the association between flooding events and the incidence of infectious diarrhea, considering diverse demographic, environmental, and pathogen-specific factors. Methods: In this systematic review and meta-analysis, adhering to PROSPERO protocol (CRD42024498899), we evaluated observational studies from January 2000 to December 2023. The analysis incorporated global data from PubMed, Scopus, Embase, Web of Science, and ProQuest, focusing on the relative risk (RR) of diarrhea post-flooding. The study encompassed diverse variables like age, sex, pathogen type, environmental context, and statistical modeling approaches. Results: The meta-analysis, involving 42 high-quality studies, revealed a substantial increase (RR = 1.40, 95% CI [1.29-1.52]) in the incidence of diarrhea following floods. Notably, bacterial and parasitic diarrheas demonstrated higher RRs (1.82 and 1.35, respectively) compared to viral etiologies (RR = 1.15). A significant sex disparity was observed, with women exhibiting a higher susceptibility (RR = 1.55) than men (RR = 1.35). Adults (over 15 years) faced a greater risk than younger individuals, highlighting age-dependent vulnerability. Conclusion: This extensive analysis confirms a significant correlation between flood events and increased infectious diarrhea risk, varying across pathogens and demographic groups. The findings highlight an urgent need for tailored public health interventions in flood-prone areas, focusing on enhanced sanitation, disease surveillance, and targeted education to mitigate this elevated risk. Our study underscores the critical importance of integrating flood-related health risks into global public health planning and climate change adaptation strategies.
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BACKGROUND: Intravenous lidocaine has shown promise as an effective analgesic in various clinical settings, but its utility for pain management in emergency departments, especially for bone fractures, remains relatively understudied. OBJECTIVE: This study compared intravenous lidocaine to pethidine for femoral bone fracture pain management. METHODS: This double-blind, randomized, controlled clinical trial was conducted in the emergency department of AJA University of Medical Sciences affiliated hospitals. Patients aged 18-70 years-old with femoral bone fracture and experiencing severe pain, defined as a numerical rating scale (NRS) of pain ≥ 7, were included in the study. One group received intravenous pethidine (25 mg), while the other group received intravenous lidocaine (3 mg/kg, not exceeding 200 mg), infused with 250 ml saline over 20 min. Pain levels were evaluated before treatment administration (0 min) and at 10, 20, 30, 40, 50, and 60 min after treatment administration using the NRS. RESULTS: Seventy-two patients were enrolled in the study. Demographic characteristics and pain scores were similar between the two groups. The mean pain scores upon arrival for the lidocaine and pethidine groups were 8.50 ± 1 and 8.0 ± 1, respectively; after one hour, they were 4.0 ± 1 and 4.0 ± 1, respectively. While there was a statistically significant reduction in pain in both groups after one hour, there were no clinically or statistically significant differences between the two groups (p = 0.262). Pethidine had a higher incidence of adverse events, though not statistically significant. Additionally, females required more rescue analgesics. CONCLUSION: The administration of intravenous lidocaine is beneficial for managing pain in femoral bone fractures, suggesting that lidocaine could be a potent alternative to opioids. TRIAL REGISTRATION: IRCT20231213060355N1 ( https://irct.behdasht.gov.ir/trial/74624 ) (30/12/2023).
Subject(s)
Analgesics, Opioid , Anesthetics, Local , Emergency Service, Hospital , Femoral Fractures , Lidocaine , Meperidine , Pain Management , Humans , Lidocaine/administration & dosage , Female , Meperidine/administration & dosage , Middle Aged , Male , Double-Blind Method , Adult , Anesthetics, Local/administration & dosage , Femoral Fractures/complications , Pain Management/methods , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Aged , Young Adult , Pain Measurement/methods , Adolescent , Administration, IntravenousABSTRACT
Recent advancements in personalized treatments, such as anthracycline chemotherapy, coupled with timely diagnoses, have contributed to a decrease in cancer-specific mortality rates and an improvement in cancer prognosis. Anthracyclines, a potent class of antibiotics, are extensively used as anticancer medications to treat a broad spectrum of tumors. Despite these advancements, a considerable number of cancer survivors face increased risks of treatment complications, particularly the cardiotoxic effects of chemotherapeutic drugs like anthracyclines. These effects can range from subclinical manifestations to severe consequences such as irreversible heart failure and death, highlighting the need for effective management of chemotherapy side effects for improved cancer care outcomes. Given the lack of specific treatments, early detection of subclinical cardiac events post-anthracycline therapy and the implementation of preventive strategies are vital. An interdisciplinary approach involving cardiovascular teams is crucial for the prevention and efficient management of anthracycline-induced cardiotoxicity. Various factors, such as age, gender, duration of treatment, and comorbidities, should be considered significant risk factors for developing chemotherapy-related cardiotoxicity. Tools such as electrocardiography, echocardiography, nuclear imaging, magnetic resonance imaging, histopathologic evaluations, and serum biomarkers should be appropriately used for the early detection of anthracycline-related cardiotoxicity. Furthermore, understanding the underlying biological mechanisms is key to developing preventive measures and personalized treatment strategies to mitigate anthracycline-induced cardiotoxicity. Exploring specific cardiotoxic mechanisms and identifying genetic variations can offer fresh perspectives on innovative, personalized treatments. This chapter aims to discuss cardiomyopathy following anthracycline therapy, with a focus on molecular mechanisms, preventive strategies, and emerging treatments.
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BACKGROUND: Inappropriate expressions of various miRNAs have reported in different human malignancies. Evidence suggested that miR-330 may play as both onco-miR and/or tumor suppressor-miR in different cancers. In the present study, we evaluated effects of miR-330 on proliferation and migration of pancreatic cancer (PC) cells as well as underlying molecular mechanisms. DESIGN: The expression of miR-330 was evaluated in clinical tissue samples of patients with PC. Transfection of the PC cells (PANC-1) by miR-330 was conducted by pCMV vector. The cancer-related genes expression was investigated in mRNA and protein level following transfection of the PC cells. Furthermore, the PC cells viability, invasion, migration, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle profile were investigated after transfection by miR-330. RESULTS: The results indicated that expression of miR-330 downregulated in patients with PC. Stable increase of miR-330 expression after transfection in PC cells reduces viability, mitochondrial membrane potential, invasion, and migration. Further assessments demonstrated that upregulation of miR-330 increases apoptosis and autophagy percentage in the PC cells. Moreover, a cell cycle arrest was observed in G1, Sub-G1, and S phases following transfection of the PC cells. These findings can be explained by modified mRNA and protein expression of apoptosis- and metastasis-related genes. CONCLUSION: Our study suggested that miR-330 acts as a tumor suppressor in PC cells, and revealed that upregulation of miR-330 may provide an effective therapeutic approach for overcoming progression and metastasis in patients with PC.
Subject(s)
Apoptosis , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , MicroRNAs , Pancreatic Neoplasms , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Apoptosis/genetics , Cell Proliferation/genetics , Cell Movement/genetics , Gene Expression Regulation, Neoplastic/genetics , Cell Line, Tumor , Carcinogenesis/genetics , Autophagy/genetics , Male , Female , Middle Aged , Membrane Potential, Mitochondrial/geneticsABSTRACT
Objective: The failure to detect PDG and lack of providing essential interventions accordingly can disrupt the lives of survivors of natural disasters years after the death of their loved ones. The present study aims to investigate PGD after natural disasters using a systematic review and meta-analysis. Study design: This study was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Methods: With the focus on the prevalence of PGD after natural disasters, studies conducted until the end of 2021 were collected without a time limit. To do this, reputable databases such as PubMed, Web of Science, Scopus, Embase, Google Scholar, and Science Direct were used. The random effects model was used to perform a meta-analysis of the studies. To check the heterogeneity between the studies, the I2 index was used. The publication bias of the study was evaluated using Begg's test. Data were analyzed using the STATA software. Results: Primarily, 2566 studies were collected based on the initial search, from which 12 final studies were entered into the analysis. The results showed that the prevalence of PGD after natural disasters was 38.81 % (95 % CI: 24.12-53.50, I2 = 99.7 %, p = 0 < 001). Conclusions: It is recommended that policies and plannings of the organizations responsible for disaster management be prepared to send specialized teams of psycho-spiritual counseling, quickly accommodate the injured, and reconstruct the damaged buildings in the shortest time possible.
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Advancements in cancer treatments have improved survival rates but have also led to increased cardiotoxicities, which can cause adverse cardiovascular events or worsen pre-existing conditions. Herein, cardiotoxicity is a severe adverse effect of 5-fluorouracil (5-FU) therapy in cancer patients, with reported incidence rates ranging from 1 to 20%. Some studies have also suggested subclinical effects and there are reports which have documented instances of cardiac arrest or sudden death during 5-FU treatment, highlighting the importance of timely management of cardiovascular symptoms. However, despite being treated with conventional medical approaches for this cardiotoxicity, a subset of patients has demonstrated suboptimal or insufficient responses. The frequent use of 5-FU in chemotherapy and its association with significant morbidity and mortality indicates the need for a greater understanding of 5-FU-associated cardiotoxicity. It is essential to reduce the adverse effects of anti-tumor medications while preserving their efficacy, which can be achieved through drugs that mitigate toxicity associated with these drugs. Underpinning cardiotoxicity associated with 5-FU therapy also has the potential to offer valuable guidance in pinpointing pharmacological approaches that can be employed to prevent or ameliorate these effects. The present study provides an overview of management strategies for cardiac events induced by fluoropyrimidine-based cancer treatments. The review encompasses the underlying molecular and cellular mechanisms of cardiotoxicity, associated risk factors, and diagnostic methods. Additionally, we provide information on several available treatments and drug choices for angina resulting from 5-FU exposure, including nicorandil, ranolazine, trimetazidine, ivabradine, and sacubitril-valsartan, which have demonstrated potential in mitigating or protecting against chemotherapy-induced adverse cardiac effects.
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Heart Diseases , Neoplasms , Humans , Cardiotoxicity , Fluorouracil/adverse effects , Heart , Heart Diseases/pathology , Neoplasms/drug therapyABSTRACT
Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer that is frequently diagnosed, is distinguished by its propensity for aggressive behavior, frequent poor response to standard therapy, and capacity to metastasize to distant areas. Utilizing the body's natural immune defense mechanisms, particularly through the use of chimeric antigen receptor (CAR) technology, is receiving increasing attention in the dynamic field of oncological therapies. Although T cells have received most of the attention, this strategy has proven to be highly effective in battling some blood-related malignancies. However, there are considerable challenges when using this method in the context of solid tumors. The innate immune system's natural killer (NK) cells are essential parts because they have the ability to detect and destroy cancer cells. CAR-NK cells are a very promising approach because they combine the natural cytotoxic properties of natural killer (NK) cells with the precise targeting skills of chimeric antigen receptor (CAR) technology. With the use of this integrated strategy, the intrinsic diversity of cutaneous squamous cell carcinoma (cSCC) tumors may be successfully targeted, increasing treatment effectiveness and lowering the risk of tumor recurrence. This tactic is improved by the development of dual-specificity chimeric antigen receptors (CARs), which fully resolve the antigen presentation heterogeneity among tumor cells. In conclusion, the use of CAR-NK cells that precisely target cSCC-specific antigens has the potential to drastically transform therapy approaches for cSCC as well as other difficult solid tumors as oncological research advances. In order to create chimeric antigen receptor (CAR)-natural killer (NK) cells that particularly target antigens linked to cutaneous squamous cell carcinoma (cSCC), the goal of this protocol is to present a detailed method. The ultimate objective is to lay the groundwork for the development of precision immunotherapy.
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Androgen deprivation therapy (ADT) remains the cornerstone of advanced prostate cancer treatment. However, the progression towards castration-resistant prostate cancer is inevitable, as the cancer cells reactivate androgen receptor signaling and adapt to the castrate state through autoregulation of the androgen receptor. Additionally, the upfront use of novel hormonal agents such as enzalutamide and abiraterone acetate may result in long-term toxicities and may trigger the selection of AR-independent cells through "Darwinian" treatment-induced pressure. Therefore, it is crucial to develop new strategies to overcome these challenges. Bipolar androgen therapy (BAT) is one such approach that has been devised based on studies demonstrating the paradoxical inhibitory effects of supraphysiologic testosterone on prostate cancer growth, achieved through a variety of mechanisms acting in concert. BAT involves rapidly alternating testosterone levels between supraphysiological and near-castrate levels over a period of a month, achieved through monthly intramuscular injections of testosterone plus concurrent ADT. BAT is effective and well-tolerated, improving quality of life and potentially re-sensitizing patients to previous hormonal therapies after progression. By exploring the mechanisms and clinical evidence for BAT, this review seeks to shed light on its potential as a promising new approach to prostate cancer treatment.
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Combination therapy is a novel cancer therapy approach that combines two or more chemotherapy drugs. This treatment modality enhances the efficacy of chemotherapy by targeting key pathways in an additive or synergistic manner. Therefore, we investigated the efficacy of combination therapy by widely used chemotherapy drug doxorubicin (DOX) and oleanolic acid (OA) to induction of apoptosis for pancreatic cancer (PC) therapy. The effects of DOX, OA, and their combination (DOX-OA) were investigated on proliferation and viability of PC cell line (PANC-1) by MTT assay. Moreover, migration and invasion of the cancer cells were evaluated by trans-well migration assay and wound healing assay. Flow cytometry and DAPI (4',6-diamidino-2-phenylindole) staining were employed to investigate apoptosis quantification and qualification of the treated cancer cells. Finally, mRNA expression of apoptosis-related genes was assessed by quantitative real-time polymerase chain reaction. Our results demonstrated that the proliferation and metastasis potential of PC cells significantly decreased after treatment by DOX, OA, and DOX-OA. Moreover, we observed an increase in apoptosis percentage in the treated cancer cells. The apoptosis-related gene expression was modified to increase the apoptosis rate in all of the treatment groups. However, the anticancer potency of DOX-OA combination was significantly more than that of DOX and OA treatments alone. Our study suggested that DOX-OA combination exerts more profound anticancer effects against PC cell lines than DOX or OA monotherapy. This approach may increase the efficiency of chemotherapy and reduce unintended side effects by lowering the prescribed dose of DOX.
Subject(s)
Oleanolic Acid , Pancreatic Neoplasms , Humans , Oleanolic Acid/pharmacology , Cell Line, Tumor , Doxorubicin/pharmacology , Apoptosis , Pancreatic Neoplasms/metabolism , Pancreatic NeoplasmsABSTRACT
AIM: In the current study, we aimed to mitigate radiation-induced small intestinal toxicity using post-irradiation treatment with nano-micelle curcumin. BACKGROUND: Small intestine is one of the most radiosensitive organs within the body. Wholebody exposure to an acute dose of ionizing radiation may lead to severe injuries to this tissue and may even cause death after some weeks. OBJECTIVE: This study aimed to evaluate histopathological changes in the small intestine following whole-body irradiation and treatment with nanocurcumin. MATERIALS AND METHODS: Forty male Nordic Medical Research Institute mice were grouped into control, treatment with 100 mg/kg nano-micelle curcumin, whole-body irradiation with cobalt-60 gamma-rays (dose rate of 60 cGy/min and a single dose of 7 Gy), and treatment with 100 mg/kg nano-micelle curcumin 1 day after whole-body irradiation for 4 weeks. Afterward, all mice were sacrificed for histopathological evaluation of their small intestinal tissues. RESULTS: Irradiation led to severe damage to villi, crypts, glands as well as vessels, leading to bleeding. Administration of nano-micelle curcumin after whole-body irradiation showed a statistically significant improvement in radiation toxicity of the duodenum, jejunum and ileum (including a reduction in infiltration of polymorphonuclear cells, villi length shortening, goblet cells injury, Lieberkühn glands injury and bleeding). Although treatment with nano-micelle curcumin showed increased bleeding in the ileum for non-irradiated mice, its administration after irradiation was able to reduce radiation-induced bleeding in the ileum. CONCLUSION: Treatment with nano-micelle curcumin may be useful for mitigation of radiationinduced gastrointestinal system toxicity via suppression of inflammatory cells' infiltration and protection against villi and crypt shortening.
Subject(s)
Curcumin , Male , Mice , Animals , Curcumin/pharmacology , Radiopharmaceuticals , Intestine, Small/pathology , Intestine, Small/radiation effects , Ileum , Intestinal Mucosa/pathology , Intestinal Mucosa/radiation effectsABSTRACT
Aim: The present double-blinded placebo-controlled randomized clinical trial evaluated prophylactic use of acetylcysteine for the prevention of liver injury in patients with severe COVID-19 pneumonia under treatment with remdesivir. Background: Liver injury is reportedly common in patients with severe COVID-19 pneumonia and can occur not only as a result of disease progression, but as an iatrogenic reaction to remdesivir. Methods: A total of 83 adult patients with severe COVID-19 pneumonia were randomly assigned in parallel groups to receive either acetylcysteine or placebo. All the patients received standard care according to institutional protocols, including remdesivir for a total of five days. One gram acetylcysteine was administered intravenously every 12 hours for 42 patients, and 41 patients received the same volume of 0.9% sodium chloride as placebo (Trial Registration: www.irct.ir identifier, IRCT20210726051995N1). Results: After 5 days, median aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in the acetylcysteine than in the placebo group. Of those who received the placebo, 30 (73.2%), 4 (9.7%), and 3 (7.3%) patients had serum AST levels elevated between 1-2.5, 2.5-5, and over 5 times the upper limit of normal (ULN), respectively; while in the acetylcysteine group, 33 (78.6%) and 0 patients had AST levels between 1-2.5 and over 2.5 times ULN, respectively (p-value=0.037). In the acetylcysteine group, 23 (54.8%), 1 (2.4%), and 1 (2.4%) patient had serum ALT levels elevated between 1-2.5, 2.5-5, and over 5 times ULN, respectively; in the placebo group, however, 24 (58.5%), 7 (17.1%), and 1 (2.4%) patient had serum ALT levels between 1-2.5, 2.5-5, and over 5 times ULN, respectively (p-value=0.073). Conclusion: Intravenous administration of acetylcysteine significantly prevents liver transaminases elevation and liver injury in seriously ill COVID-19 patients treated with remdesivir.
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Considering the outbreak pandemic of Coronavirus Disease 2019 (COVID-19), the lack of effective therapeutic strategies for the management of this viral disease, and the increasing evidence on the antiviral potential of silymarin, this study aimed to investigate the effectiveness of silymarin nanomicelles on the symptom's resolution time, laboratory parameters, and liver enzymes in patients with COVID-19. The participants were assigned to the nano-silymarin (n = 25) (receiving SinaLive soft gel, containing 70 mg silymarin as nanomicelles) or placebo groups (n = 25) three times daily for two weeks. Patients' symptoms and laboratory findings were assessed at baseline and during the follow-up period (one week and one month after the beginning of the treatment). No significant differences were observed between the two groups in terms of symptoms resolution time, laboratory parameters, and hospitalization duration (p > 0.05). However, the alanine aminotransferase level decreased significantly in the treatment group, compared to the placebo group (p < 0.001). Concomitant use of dexamethasone and remdesivir with silymarin might make the effects of silymarin on the improvement of patients' condition unclear. Further clinical trials are recommended with diverse dosages and larger sample sizes.
Subject(s)
COVID-19 Drug Treatment , Silymarin , Alanine Transaminase , Antiviral Agents/therapeutic use , Dexamethasone/therapeutic use , Double-Blind Method , Humans , SARS-CoV-2 , Silymarin/therapeutic use , Treatment OutcomeABSTRACT
The COVID-19 pandemic has prompted researchers to find treatments and vaccines to control SARS-CoV-2. There are some hypotheses about the benefit of respiratory virus vaccines, like MMR, for COVID-19 pneumonia severity, morbidity, and mortality. The influenza vaccine is one of the most frequently used respiratory virus vaccines covered by one of the Iranian insurance institutes. We have a symmetrical group of participants that have received this vaccine that could be compared with each other. We compared 3,379 persons aged 20 - 75 years for the effect of the influenza vaccine on COVID-19 mortality. We ultimately found that it does not affect mortality caused by COVID-19 pneumonia, but it can decrease the hospitalization cost in people over 65 years with a history of chronic disease.
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OBJECTIVES: Evaluation of the incidence of infectious diseases after natural disasters can help develop healthcare policies. This study provides a global review of the most prevalent infectious diseases observed after earthquakes. STUDY DESIGN: A systematic review and meta-analysis were performed. METHODS: A systematic review was performed on electronic databases, including PubMed, Scopus and Web of Science, up to March 2020 (with no time limitations). Studies addressing earthquakes and infectious diseases were collected based on specified inclusion and exclusion criteria. Subsequently, the quality of the studies was assessed by the Newcastle-Ottawa scale (NOS). Data analyses were carried out on six subgroups under five different disease categories using comprehensive meta-analysis software. RESULTS: In total, 24 studies qualified for the systematic review and 18 were included in the meta-analysis. The incidences of gastrointestinal infections, dermal infections, respiratory infections, central nervous system infections and other infectious diseases were as follows: odds ratio (OR) 163.4 (95% confidence interval [CI]: 31.0-858.1), OR 84.5 (95% CI: 27.1-262.8), OR 9.9 (95% CI: 3.5-27.7), OR 0.5 (95% CI: 0.2-1.1) and OR 4.4 (95% CI: 1.9-9.9) cases per 100,000 people, respectively. The association between the incidences of infectious diseases before and after earthquakes was significant, namely, 1.561 (95% CI: 1.244-1.957) with a P-value <0.001. CONCLUSIONS: The results show an increase in the prevalence of infectious diseases after earthquakes. Governments should take essential measures to be better prepared for such unpredictable catastrophes.
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Communicable Diseases , Earthquakes , Respiratory Tract Infections , Humans , Incidence , PrevalenceABSTRACT
Reperfusion therapies are recommended for patients with hemodynamic instability or high-risk acute pulmonary embolism (PE). Lower doses of tissue plasminogen activator (rt-PA) could be considered to improve bleeding complications. The aim of this study was to evaluate the efficacy and safety of a reduced dose of rt-PA for the treatment of acute PE, compared with anticoagulation and standard dose. PubMed Central, Scopus, Web of Science and Embase were searched for all relevant randomized studies and prospective observational studies that compared reduced dose of rt-PA with anticoagulation alone or standard dose of rt-PA in patients with acute PE. The risk ratios (RR, with 95% CI) were calculated according to the value of I2. Outcomes were described as bleeding events, all-cause death, and recurrence of PE. Thirteen articles, including four observational studies (4223 patients) and nine RCTs (780 patients), were included. In comparing reduced dose of rt-PA with anticoagulant, a greater incidence of total bleeding events in low dose was showed (RR, 5.08 (95% CI, (1.39-18.6), I2 = 0.0%). In the standard dose rt-PA vs. reduced dose, there was a greater incidence of total bleeding events in the standard dose of rt-PA, RR 1.48 (95% CI, (1.00-2.19), I2 = 0.0%) was shown. There were no statistical differences in recurrent PE or all-cause mortality. It concluded that in the absence of the benefit of a standard dose of rt-PA in comparison with dose reduction, a reduced dose of rt-PA showed a lower rate of total bleeding events and similar efficacy regarding mortality and PE recurrence rate.
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OBJECTIVES: Currently published papers and clinical guidelines regarding the effects of tocilizumab in severe and critical COVID-19 are contradictory. The aim of this meta-analysis was to combine the results of clinical studies of different designs to investigate the efficacy and safety of tocilizumab in severely-to-critically ill COVID-19 patients. METHODS: A systematic search was performed in PubMed, Embase, CENTRAL, ClinicalTrials.gov, Scopus, and preprint servers up to 26 December 2020. Since a substantial heterogeneity was expected, a random-effects model was applied to calculate the pooled effect size (ES) and 95% confidence interval (CI) for each study outcome. RESULTS: Forty-five comparative studies involving 13,189 patients and 28 single-arm studies involving 1,770 patients were analyzed. The risk of mortality (RR of 0.76 [95%CI 0.65 to 0.89], P < 0.01) and intubation (RR of 0.48 [95%CI 0.24 to 0.97], P = 0.04) were lower in tocilizumab patients compared with controls. We did not find any significant difference in secondary infections, length of hospital stay, hospital discharge before day 14, and ICU admission between groups. CONCLUSION: Tocilizumab can improve clinical outcomes and reduce mortality rates in severe to critical COVID-19 patients. Large-scale randomized controlled trials are still required to improve the statistical power of meta-analysis.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Drug Treatment , SARS-CoV-2 , Severity of Illness Index , Antibodies, Monoclonal, Humanized/adverse effects , HumansABSTRACT
BACKGROUND: We examined the safety and efficacy of a treatment protocol containing Favipiravir for the treatment of SARS-CoV-2. METHODS: We did a multicenter randomized open-labeled clinical trial on moderate to severe cases infections of SARS-CoV-2. Patients with typical ground glass appearance on chest computerized tomography scan (CT scan) and oxygen saturation (SpO2) of less than 93% were enrolled. They were randomly allocated into Favipiravir (1.6 gr loading, 1.8 gr daily) and Lopinavir/Ritonavir (800/200 mg daily) treatment regimens in addition to standard care. In-hospital mortality, ICU admission, intubation, time to clinical recovery, changes in daily SpO2 after 5 min discontinuation of supplemental oxygen, and length of hospital stay were quantified and compared in the two groups. RESULTS: 380 patients were randomly allocated into Favipiravir (193) and Lopinavir/Ritonavir (187) groups in 13 centers. The number of deaths, intubations, and ICU admissions were not significantly different (26, 27, 31 and 21, 17, 25 respectively). Mean hospital stay was also not different (7.9 days [SD = 6] in the Favipiravir and 8.1 [SD = 6.5] days in Lopinavir/Ritonavir groups) (p = 0.61). Time to clinical recovery in the Favipiravir group was similar to Lopinavir/Ritonavir group (HR = 0.94, 95% CI 0.75 - 1.17) and likewise the changes in the daily SpO2 after discontinuation of supplemental oxygen (p = 0.46) CONCLUSION: Adding Favipiravir to the treatment protocol did not reduce the number of ICU admissions or intubations or In-hospital mortality compared to Lopinavir/Ritonavir regimen. It also did not shorten time to clinical recovery and length of hospital stay.
Subject(s)
Amides/administration & dosage , Amides/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , COVID-19 Drug Treatment , Pyrazines/administration & dosage , Pyrazines/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Intubation , Kaplan-Meier Estimate , Length of Stay , Lopinavir/administration & dosage , Lopinavir/adverse effects , Male , Middle Aged , Oxygen/blood , Ritonavir/administration & dosage , Ritonavir/adverse effects , Severity of Illness Index , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: The newly emerged coronavirus disease 2019 (COVID-19) seems to involve different organs, including the cardiovascular system. We systematically reviewed COVID-19 cardiac complications and calculated their pooled incidences. Secondarily, we compared the cardiac troponin I (cTnI) level between the surviving and expired patients. METHODS: A systematic search was conducted for manuscripts published from December 1, 2019 to April 16, 2020. Cardiovascular complications, along with the levels of cTnI, creatine kinase (CK), and creatine kinase MB (CK-MB) in hospitalized PCR-confirmed COVID-19 patients were extracted. The pooled incidences of the extracted data were calculated, and the unadjusted cTnI level was compared between the surviving and expired patients. RESULTS: Out of 1094 obtained records, 22 studies on a total of 4,157 patients were included. The pooled incidence rate of arrhythmia was 10.11%. Furthermore, myocardial injury had a pooled incidence of 17.85%, and finally, the pooled incidence for heart failure was 22.34%. The pooled incidence rates of cTnI, CK-MB, and CK elevations were also reported at 15.16%, 10.92%, and 12.99%, respectively. Moreover, the pooled level of unadjusted cTnI was significantly higher in expired cases compared with the surviving (mean difference = 31.818, 95% CI = 17.923-45.713, P value <0.001). CONCLUSION: COVID-19 can affect different parts of the heart; however, the myocardium is more involved.