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1.
EClinicalMedicine ; 49: 101484, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1881934

ABSTRACT

Background: The effectiveness of combination therapy for COVID-19 pneumonia remains unclear. We evaluated favipiravir, camostat, and ciclesonide combination therapy in patients with moderate COVID-19 pneumonia. Methods: In this open-label phase 3 study, hospitalized adults who were positive for SARS-CoV-2 and had COVID-19 pneumonia were enrolled prior to official vaccination drive in Japan. Participants were randomly assigned to favipiravir monotherapy or favipiravir + camostat + ciclesonide combination therapy. The primary outcome was the length of hospitalization due to COVID-19 infection after study treatment. The hospitalization period was calculated from the time of admission to the time of patient discharge using the clinical management guide of COVID-19 for front-line healthcare workers developed by the Japanese Ministry of Health, Labour, and Welfare (Version 3). Cases were registered between November 11, 2020, and May 31, 2021. Japan Registry of Clinical Trials registration: jRCTs031200196. Findings: Of 121 enrolled patients, 56 received monotherapy and 61 received combination therapy. Baseline characteristics were balanced between the groups. The median time of hospitalization was 10 days for the combination and 11 days for the monotherapy group. The median time to discharge was statistically significantly lower in the combination therapy vs monotherapy group (HR, 1·67 (95% CI 1·03-2·7; P = 0·035). The hospital discharge rate was statistically significantly higher in the combination therapy vs monotherapy group in patients with less severe COVID-19 infections and those who were ≤60 years. There were no significant differences in clinical findings between the groups at 4, 8, 11, 15, and 29 days. Adverse events were comparable between the groups. There were two deaths, with one in each group. Interpretation: Combination oral favipiravir, camostat and, ciclesonide therapy could decrease the length of hospitalization stays without safety concerns in patients with moderate COVID-19 pneumonia. However, lack of hard clinical primary outcome is one of the major limitations of the study. Funding: This research was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 20fk0108261h0001.

2.
Vnitr Lek ; 67(7): 412-418, 2021.
Article in English | MEDLINE | ID: covidwho-1801786

ABSTRACT

Cardiovascular diseases (not including COVID-19 infection) are still one of the most common causes of mortality and morbidity in our country and in developed countries. Today no one questions the intervention of all risk factors for atherosclerosis after a cardiovascular event, although unfortunately even in this case the recommended target values are often not achieved. However, the intervention of risk factors in primary prevention is often neglected. Atherosclerosis is a long-term process, developing since the childhood. It is a continuous process and the event itself is only the culmination of this process. Therefore, it is necessary to intervene in key risk factors early in life, and we have ample evidence that even early pharmacological intervention has a clear effect on slowing or stopping the process of atherosclerosis.


Subject(s)
Atherosclerosis , COVID-19 , Cardiovascular Diseases , Dyslipidemias , Hypertension , Atherosclerosis/complications , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Child , Dyslipidemias/complications , Dyslipidemias/drug therapy , Humans , Hypertension/complications , Hypertension/drug therapy , Risk Factors
3.
Acta Pharmaceutica ; 72(3):345-358, 2022.
Article in English | ProQuest Central | ID: covidwho-1789317

ABSTRACT

Coronavirus disease 2019 (COVID-19) was reported as a global pandemic in March 2020 after invading many countries and leaving behind tens of thousands of infected patients in a brief time span. Approval of a few vaccines has been obtained and their efficacy of varying degrees established. Still, there is no effective pharmaceutical agent for the treatment of COVID-19 though several drugs are undergoing clinical trials. Recent studies have shown that dexamethasone, a corticosteroid, can reduce the rate of COVID-19-related mortality in the intensive care unit by 35 % for patients who are on mechanical ventilation. Although variable efficacy of other combination therapies has been reported for treating COVID-19 associated with acute respiratory distress syndrome (ARDS), dexamethasone is an extensively used drug in many treatment regimens against COVID-19. The current review aims to explore the role of dexamethasone as an efficient combination treatment for COVID-19.

4.
J Infect Public Health ; 15(5): 566-572, 2022 May.
Article in English | MEDLINE | ID: covidwho-1763843

ABSTRACT

An unprecedented global health crisis has developed due to the emergence of the mysterious coronavirus-2 of the severe acute respiratory syndrome, which has resulted in millions of deaths around the globe, as no therapy could control the 'cytokine storm'. Consequently, many vaccines have been developed and several others are being developed for this infection. Although most of the approved vaccines have been highly effective, many developing, and economically poor countries are still deprived of vaccination against SARS-CoV-2 due to the unequal distribution of vaccines worldwide. Furthermore, the uncertainty about the effectiveness of the available vaccines against the emerging mutants and variants also remains a matter of concern. Due to the multistep pathogenesis and unique features, combination therapy using safe immunomodulatory and antiviral drugs should be considered as the most effective and acceptable therapeutic regimen for this infection. Based on a thorough assessment of the literature, it was determined that it would be interesting to study the therapeutic potential of ivermectin and doxycycline, given their roles in several biological pathways involved in SARS CoV-2 pathogenesis. Following that, a comprehensive literature search was undertaken using Scopus, Web of Science, and Pubmed, depending on the inclusion and exclusion criteria. The present study provides a mechanism and comprehensive report, highlighting the role of combined therapy with ivermectin and doxycycline in alleviating the 'cytokine storm' of COVID-19 infection.


Subject(s)
COVID-19 , Cytokine Release Syndrome , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/prevention & control , Doxycycline/therapeutic use , Humans , Ivermectin/therapeutic use , SARS-CoV-2 , Vaccination
5.
Non-conventional in English | National Technical Information Service, Grey literature | ID: grc-753616

ABSTRACT

Chemo resistance is a major cause of the high mortality of ovarian cancer. For example, although high-grade serous ovarian carcinoma (HGSOC) initially responds well to platinum-based chemotherapy, relapse often occurs with decreased chemotherapeutic sensitivity. Substantial evidence suggests that cancer stem-like cells (CSC) contribute to chemotherapy resistance. Putative epithelial ovarian cancer (EOC) CSCs are typically characterized by increased aldehyde dehydrogenase (ALDH) activity due to concomitant upregulation of the ALDH1A1 gene. It has been demonstrated preclinically that suppression of ALDH activity by ALDH1A1 knock-down sensitizes EOC cells to chemotherapy, demonstrating the functional importance of ALDH activity in EOC chemo resistance. We have furthermore shown that BRD4 (BET) inhibition reduces ALDH activity, thereby eradicating CSCs. The mechanism of suppression of ALDH activity is through down regulation of the ALDH1A1 super-enhancer associated non-coding enhancer RNA (eRNA). Notably, BRD4 genomic locus 19p13.12 is often amplified in HGSOC (~20%), and amplification/overexpression correlates with a poor prognosis in HGSOC patients. Therefore, we hypothesize that BRD4/BET inhibition may overcome chemotherapy resistance, and plan a phase I clinical trial to evaluate the combination of BET inhibitor INCB57643 (Incyte, Inc.) with carboplatin into establish MTD, tolerability, and preliminary efficacy of the combination. We propose embedded correlative science to identify populations most likely to respond to therapy. Our central hypothesis is that platinum resistance can be overcome through eliminating ALDH positive cancer stem-like cells by targetingBRD4 through BET inhibition. The goals of the proposal are: 1) To conduct a Phase I clinical trial of combined BET inhibitor (INCB57643) and carboplatin inpatients with platinum-resistant HGSOC. 2) To identify companion biomarkers that correlate with response to combination therapy in HGSOC patients.

6.
Non-conventional in English | National Technical Information Service, Grey literature | ID: grc-753600

ABSTRACT

Despite some interruptions in workflow and data acquisition due to the COVID pandemic, we made substantial progress this past year towards our aims. We completed most of the studies in aims 1 and 2 to compare our panel of viruses in one (#5NPCIS) of the two tumor models. We found that TVEC had the most ability to replicate in cell lines, but by other parameters the three viruses functioned similarly in their relative lack of therapeutic efficacy as a single agent despite induction of immune cell chemoattractant chemokines and immune cell infiltration. We encountered unforeseen challenges in growing the second model (67C-4), but those have largely been solved and we are now poised to complete aims 1 and 2 using that model in the final year of the project. We also conducted studies in the first model of combinationtherapy as planned in aim 2, but also found no combination efficacy. These results were surprising to us, as the combination has shown activity in other tumors types, including a model of rhabdomyosarcoma which is also an NF-1 related tumor. Again, we will test combination therapy as described in aim 2 in the second model in the coming year of the grant. Finally, we also made progress on aim 3 using virus plus ruxolitinib, and plan to complete those studies in the next reporting period.

7.
Non-conventional in English | National Technical Information Service, Grey literature | ID: grc-753493

ABSTRACT

We have found ART1 expressed in multiple human non-small cell lung cancer (NSCLC) cell lines and in mouse and human NSCLC tumors. ART1, an ARTC family mono-ADP-ribosyltransferase, functions extracellularly to target arginine-rich cell surface proteins on neighboring cells or target soluble proteins in the local tumor microenvironment. Following ART1 knockdown in murine immune competent lung cancer models, we note a highly significant increase in cytotoxic tumor infiltrating CD8 T cells and a subsequent decrease in tumor burden. Mono-ADP-ribosylation of the P2X7 receptor on subsets of CD8 T cells may induce receptor activation and apoptosis, a process described as NAD-induced cell death (NICD). ART1-induced mono-ADP-ribosylation of P2X7R could therefore allow cancer cells overexpressing ART1 to blunt the T cell immune response against them by inducing T cell apoptosis. Although little is known about ART1 in human cancer, its expression may be upregulated by ER stress and its enzymatic activity increased by release of NAD into the local microenvironment, both of which occur following cytotoxic cancer therapy, particularly radiation therapy. In the current application addressing the LCRP Area of Emphasis Identify innovative strategies for prevention and treatment of lung cancer, we therefore propose to evaluate the therapeutic efficacy of anti-ART1 antibodies which we have already developed and functionally optimized and to determine whether ART1 blockade has additive anti-tumor effects to immune checkpoint blockade and radiation therapy. We hypothesize that therapeutic inhibition of ART1 with an anti-ART1 monoclonal antibody will promote immune mediated rejection of lung cancer. Moreover, we hypothesize that ART1 inhibition combined with radiation therapy will demonstrate synergistic anti-tumor effects.

8.
Non-conventional in English | National Technical Information Service, Grey literature | ID: grc-753463

ABSTRACT

Despite current aggressive regimens, the majority of patients with MYCN amplification die due to drug-resistant disease, and further intensification ofchemotherapy will not significantly improve this outcome. We propose an entirely novel strategy to oppose MYCN oncogenic function in NB: by blockingthe metabolic reprogramming driven by MYCN. Based on our data and the recent literature, our guiding hypotheses are that: a) lipid metabolism is requiredfor NB tumorigenesis, and b) targeting MYCN-driven lipogenesis will effectively block NB tumor growth. We have demonstrated that lipid metabolism is aselective metabolic dependency of MYCN-driven tumors. MYCN drives both fatty acid (FA) synthesis and FA uptake to maintain NB cell survival. TargetingFA uptake effectively blocks NB in vivo tumor growth.

9.
Front Pharmacol ; 12: 743486, 2021.
Article in English | MEDLINE | ID: covidwho-1725416

ABSTRACT

Background: Severe pneumonia (SP) has a high mortality rate and is responsible for significant healthcare costs. Chinese herbal injections (CHIs) have been widely used in China as a novel and promising treatment option for SP. Therefore, this study assessed and ranked the effectiveness of CHIs to provide more sights for the selection of SP treatment. Method: Seven databases were searched from their inception up to April 1, 2021. The methodological quality of included study was evaluated by the Cochrane risk-of-bias tool. Then, a Bayesian network meta-analysis (NMA) was performed by OpenBUGS 3.2.3 and STATA 14.0 software. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. A clustering analysis was utilized to compare the effect of CHIs between two different outcomes. Results: A total of 64 eligible randomized controlled trials (RCTs) involving 5,904 participants were identified for this analysis. Six CHIs including Xuebijing injection (XBJ), Tanreqing injection (TRQ), Reduning injection (RDN), Xiyanping injection (XYP), Shenfu injection (SF), and Shenmai injection (SM) were included. The results of the NMA showed that XBJ [odds ratio (OR) = 0.24, 95% credible interval (CI): 0.19, 0.30], TRQ (OR = 0.22, 95% CI: 0.12, 0.37), RDN (OR = 0.29, 95% CI: 0.04, 0.94), and SM (OR = 0.27, 95% CI: 0.08, 0.63) combined with conventional Western medicine (WM) improved the clinical effective rate more significantly than WM alone. Based on SUCRA values, TRQ + WM (SUCRA: 66.4%) ranked the highest in improving the clinical effective rate, second in four different outcomes, and third in only one. According to the cluster analysis, TRQ + WM exerted a positive effect on improving the efficacy of SP. As for safety, less than 30% (18 RCTs) of the included studies reported adverse drug reactions/adverse drug events (ADRs/ADEs), including 14 RCTs of XBJ, 3 RCTs of TRQ, and 1 RCT of RDN. Conclusion: In conclusion, the study found that the CHIs as co-adjuvant therapy could be beneficial for patients with SP. TRQ + WM showed an outstanding improvement in patients with SP considering both the clinical effective rate and other outcomes. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021244587].

10.
Viruses ; 14(2)2022 02 08.
Article in English | MEDLINE | ID: covidwho-1674832

ABSTRACT

An escalating pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely impacted global health. There is a severe lack of specific treatment options for diseases caused by SARS-CoV-2. In this study, we used a pseudotype virus (pv) containing the SARS-CoV-2 S glycoprotein to screen a botanical drug library containing 1037 botanical drugs to identify agents that prevent SARS-CoV-2 entry into the cell. Our study identified four hits, including angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid, as effective SARS-CoV-2 S pv entry inhibitors in the micromolar range. A mechanistic study revealed that these four agents inhibited SARS-CoV-2 S pv entry by blocking spike (S) protein-mediated membrane fusion. Furthermore, angeloylgomisin O and schisandrin B inhibited authentic SARS-CoV-2 with a high selective index (SI; 50% cytotoxic concentration/50% inhibition concentration). Our drug combination studies performed in cellular antiviral assays revealed that angeloylgomisin O has synergistic effects in combination with remdesivir, a drug widely used to treat SARS-CoV-2-mediated infections. We also showed that two hits could inhibit the newly emerged alpha (B.1.1.7) and beta (B.1.351) variants. Our findings collectively indicate that angeloylgomisin O and schisandrin B could inhibit SARS-CoV-2 efficiently, thereby making them potential therapeutic agents to treat the coronavirus disease of 2019.


Subject(s)
Antiviral Agents/pharmacology , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Small Molecule Libraries/pharmacology , Virus Internalization/drug effects , Animals , COVID-19/drug therapy , Caco-2 Cells , Cell Line , Chlorocebus aethiops , Cricetinae , Drug Discovery , HEK293 Cells , Humans , Vero Cells
11.
Hum Vaccin Immunother ; 18(1): 2024416, 2022 12 31.
Article in English | MEDLINE | ID: covidwho-1672019

ABSTRACT

After one year of absence, the 18th Annual Meeting of the Association for Cancer Immunotherapy (CIMT), Europe's cancer immunotherapy meeting, took place virtually from 10 to 12 May 2021. Over 850 academic and clinical professionals from 30 countries met to discuss the recent advancements in cancer immunotherapy and the current progress in COVID19-related research. This meeting report summarizes the highlights of CIMT2021.


Subject(s)
COVID-19 , Neoplasms , Humans , Immunotherapy , Neoplasms/therapy , Tumor Microenvironment
12.
Adv Exp Med Biol ; 1352: 211-222, 2021.
Article in English | MEDLINE | ID: covidwho-1669705

ABSTRACT

INTRODUCTION: Excessive inflammatory responses and failed resolution are major common causes of tissue injury and organ dysfunction in a variety of diseases, including multiple sclerosis (MS), diabetes, and most recently, COVID-19, despite the distinct pathoetiology of the diseases. The promotion of the natural process of inflammatory resolution has been long recognized to improve functional recovery and disease outcomes effectively. To mitigate the excessive inflammation in MS, scientific investigations identified a group of derivatives of omega fatty acids, known as specialized pro-resolving lipid mediators (SPM) that have been significantly effective in treating preclinical disease models of MS. METHODS: This chapter is based on our observations from MS. It is being increasingly deliberated that the ongoing COVID-19 infection induces severe cytokine storm that ultimately triggers rampant inflammation. The impact of infection and associated mortality is much higher in patients with co-morbid diseases. Also, reports suggest a better outcome in diabetic patients with reasonable glycemic control, which certainly hints towards a hidden role of anti-hyperglycemic drugs such as metformin in alleviating disease pathology through its anti-inflammatory feature. Notably, SPM and metformin share common therapeutic features in exerting a broad-spectrum anti-inflammatory activity in human patients with a superior safety profile. RESULTS: When there is an immediate need to encounter the fast-rampant infection of COVID-19 and control the viral-infection associated morbid inflammatory cytokine storm causing severe organ damage, SPM and metformin should be seriously considered as a potential adjunctive treatment. CONCLUSION: Given the fact that current treatment for COVID-19 is only supportive, global research is aimed at developing safe and effective therapeutic options that can result in a better clinical course in patients with comorbid conditions. Accordingly, taking a cue from our experiences in controlling robust inflammatory response in MS and diabetes by simultaneously inhibiting inflammatory process and stimulating its resolution, combinatorial therapy of metformin and SPM in COVID-19 holds significant promise in treating this global health crisis.


Subject(s)
COVID-19 , Cytokine Release Syndrome , Multiple Sclerosis , COVID-19/complications , Cytokine Release Syndrome/virology , Humans , SARS-CoV-2
13.
Int J Antimicrob Agents ; 59(3): 106542, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1654507

ABSTRACT

A key element for the prevention and management of coronavirus disease 2019 is the development of effective therapeutics. Drug combination strategies offer several advantages over monotherapies. They have the potential to achieve greater efficacy, to increase the therapeutic index of drugs and to reduce the emergence of drug resistance. We assessed the in vitro synergistic interaction between remdesivir and ivermectin, both approved by the US Food and Drug Administration, and demonstrated enhanced antiviral activity against severe acute respiratory syndrome coronavirus-2. Whilst the in vitro synergistic activity reported here does not support the clinical application of this combination treatment strategy due to insufficient exposure of ivermectin in vivo, the data do warrant further investigation. Efforts to define the mechanisms underpinning the observed synergistic action could lead to the development of novel treatment strategies.


Subject(s)
COVID-19 , SARS-CoV-2 , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Ivermectin/pharmacology , Ivermectin/therapeutic use
14.
AIDS Rev ; 24(1): 41-49, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1650093

ABSTRACT

Vaccines and antivirals are the classical weapons deployed to contain, prevent, and treat life-threatening viral illnesses. Specifically, for SARS-CoV-2 infection, vaccines protect against severe COVID-19 disease manifestations and complications. However, waning immunity and emergence of vaccine escape mutants remains a growing threat. This is highlighted by the current surge of the omicron COVID-19 variant. Thus, there is a race to find treatment alternatives. We contend that oral small molecule antivirals that halt SARSCoV- 2 infection are essential. Compared to currently available monoclonal antibodies and remdesivir, where parenteral administration is required, oral antivirals offer treatments in an outpatient setting with dissemination available on a larger scale. In response to this need at 2021's end, regulatory agencies provided emergency use authorization for both molnupiravir and nirmatrelvir. These medicines act on the viral polymerase and protease, respectively. Each is given for 5 days and can reduce disease progression by 30% and 89%, respectively. The advent of additional oral antivirals, the assessment of combination therapies, the formulation of extended-release medications, and their benefit for both early treatment and prophylaxis will likely transform the landscape of the COVID-19 pandemic.


Subject(s)
COVID-19 , HIV Infections , Antiviral Agents/therapeutic use , COVID-19/drug therapy , HIV Infections/drug therapy , Humans , Pandemics/prevention & control , SARS-CoV-2
15.
Chinese Journal of Nosocomiology ; 31(21):3699-3702, 2021.
Article in Chinese | GIM | ID: covidwho-1628297

ABSTRACT

OBJECTIVE: To observe the clinical efficacy and safety of the intradermal acupuncture combined with western medicine treatment of three severe crona virus disease 2019 (COVID-19). METHODS: The clinical data of three severe COVID-19 confirmed patients were retrospectively analyzed.On the basis of conventional western medical treatment, intradermal embedding treatment was used for the Kongzu, Dazhui, and Feishu points. Lung CT reports of patients before and after treatment were compared, including the percentage of neutrophil, lymphocyte, hypersensitive C-reactive protein, oxygen index and other indicators. RESULTS: The three severe COVID-19 patients were discharged from hospital after treatment with significant relief of symptoms. Lung CT re-examination showed absorption of lesions and normal inflammatory indicators, and nucleic acid reexamination was negative. CONCLUSION: At present, elderly patients with severe COVID-19 have complicated conditions and high mortality. As an auxiliary means, intradermal acupuncture combined with western medicine therapy is simple, safe and effective in the treatment of severe COVID-19, which is a new exploration for the treatment of complicated COVID-19 conditions.

16.
Vestnik KAZNMU ; 4:72-75, 2020.
Article in Russian | GIM | ID: covidwho-1628004

ABSTRACT

This study performed a systematic review and meta-analysis of 1092 COVID-19 patients treated with tocilizumab. The features of clinical symptoms, complications and outcomes of COVID-19 were analyzed.

17.
Pharmaceuticals (Basel) ; 15(1)2022 Jan 14.
Article in English | MEDLINE | ID: covidwho-1631487

ABSTRACT

Since psoriasis (PsO) is a chronic inflammatory disease, patients may experience a drug failure also with very effective drugs (i.e., secukinumab) and, consequently, dermatologists have two therapeutic options: switching or perform a combination therapy (rescue therapy) to save the drug that had decreased its efficacy. At the moment no studies focused on combination/rescue therapy of secukinumab, so we performed a 52-weeks multicenter retrospective observational study that involved 40 subjects with plaque psoriasis that experienced a secondary failure and were treated with combination therapy (ciclosporin (n = 11), MTX (n = 15), NB-UVB (n = 7) and apremilast (n = 7)). After 16 weeks of rescue/combination therapy, PASI and a DLQI varied respectively from 8 [7.0-9.0] and 13 [12.0-15.0], to 3 [2.8-4.0] and 3 [2.0-3.3]), suggesting a significant improvement of daily functionality and quality of life. Results were maintained at 52 weeks. No side effects were experienced during the study. Secukinumab remains a safety and effective drug for PsO patients also in the IL-23 and JAK inhibitors era. The rescue therapy is a valid therapeutic option in case of secukinumab secondary failure.

18.
Appl Microbiol Biotechnol ; 105(24): 9047-9067, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1530288

ABSTRACT

The rise in multi-drug resistant bacteria and the inability to develop novel antibacterial agents limits our arsenal against infectious diseases. Antibiotic resistance is a global issue requiring an immediate solution, including the development of new antibiotic molecules and other alternative modes of therapy. This article highlights the mechanism of bacteriophage treatment that makes it a real solution for multidrug-resistant infectious diseases. Several case reports identified phage therapy as a potential solution to the emerging challenge of multi-drug resistance. Bacteriophages, unlike antibiotics, have special features, such as host specificity and do not impact other commensals. A new outlook has also arisen with recent advancements in the understanding of phage immunobiology, where phages are repurposed against both bacterial and viral infections. Thus, the potential possibility of phages in COVID-19 patients with secondary bacterial infections has been briefly elucidated. However, significant obstacles that need to be addressed are to design better clinical studies that may contribute to the widespread use of bacteriophage therapy against multi-drug resistant pathogens. In conclusion, antibacterial agents can be used with bacteriophages, i.e. bacteriophage-antibiotic combination therapy, or they can be administered alone in cases when antibiotics are ineffective.Key points• AMR, a consequence of antibiotic generated menace globally, has led to the resurgence of phage therapy as an effective and sustainable solution without any side effects and high specificity against refractory MDR bacterial infections.• Bacteriophages have fewer adverse reactions and can thus be used as monotherapy as well as in conjunction with antibiotics.• In the context of the COVID-19 pandemic, phage therapy may be a viable option.


Subject(s)
Bacteriophages , COVID-19 , Anti-Bacterial Agents/therapeutic use , Humans , Pandemics , Prospective Studies , SARS-CoV-2
19.
Acta Diabetol ; 59(4): 501-508, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1520359

ABSTRACT

AIMS: To report the effect of simultaneous intravitreal dexamethasone (DEX) and aflibercept for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 102 eyes of 81 patients with DME. Patients were selected into two groups. The control group consisted of 50 eyes treated with aflibercept alone, and the combination group consisted of 52 eyes treated with simultaneous DEX implant and aflibercept injection. The primary endpoints were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 6. The secondary endpoint was the interval of retreatment. RESULTS: Baseline BCVA increased and CRT decreased at 6 months in both groups. Pseudophakic eyes in the combination group exhibited significantly greater BCVA improvement compared with phakic eyes (p = 0.031). Fewer intravitreal treatments were required for eyes treated with combination therapy than for those treated with aflibercept alone (1.56 ± 0.54 vs. 4.04 ± 1.26, p < .0001), with a mean retreatment interval of 3.66 ± 0.69 months. CONCLUSIONS: Simultaneous intravitreal DEX and aflibercept achieved non-inferior improvement of visual and anatomic outcomes compared with aflibercept alone for DME, but exhibited a significantly longer treatment interval and superior visual outcome in pseudophakic eyes. This therapeutic approach is considered a valid strategy for treating DME in the era of COVID-19.


Subject(s)
COVID-19 , Diabetic Retinopathy , Macular Edema , Angiogenesis Inhibitors , COVID-19/drug therapy , Dexamethasone , Diabetic Retinopathy/complications , Diabetic Retinopathy/drug therapy , Drug Implants , Glucocorticoids , Humans , Intravitreal Injections , Macular Edema/complications , Macular Edema/etiology , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Retrospective Studies , SARS-CoV-2 , Tomography, Optical Coherence , Treatment Outcome , Visual Acuity
20.
Biomedicines ; 9(11)2021 Nov 04.
Article in English | MEDLINE | ID: covidwho-1502360

ABSTRACT

The ongoing SARS-CoV-2 pandemic is a serious threat to public health worldwide and, to date, no effective treatment is available. Thus, we herein review the pharmaceutical approaches to SARS-CoV-2 infection treatment. Numerous candidate medicines that can prevent SARS-CoV-2 infection and replication have been proposed. These medicines include inhibitors of serine protease TMPRSS2 and angiotensin converting enzyme 2 (ACE2). The S protein of SARS-CoV-2 binds to the receptor in host cells. ACE2 inhibitors block TMPRSS2 and S protein priming, thus preventing SARS-CoV-2 entry to host cells. Moreover, antiviral medicines (including the nucleotide analogue remdesivir, the HIV protease inhibitors lopinavir and ritonavir, and wide-spectrum antiviral antibiotics arbidol and favipiravir) have been shown to reduce the dissemination of SARS-CoV-2 as well as morbidity and mortality associated with COVID-19.

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