Therapeutic Management of COVID-19 Patients

Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCov-2) or COVID-19 is a pandemic that appeared in December 2019 in China and which is an RNA virus. It gave rise to a major health crisis at the start of 2020, with numerous hospitalizations. It was quickly important to understand the pathophysiology of this viral attack on the human body in order to be able to develop treatment. However, there is no vaccine or effective therapeutic agent against SARS-CoV-2. Most of the therapeutic strategies used to deal with this virus come from the work of previous epidemics of SARS, and other influenza viruses, such as antiviral therapies (chloroquine, hydroxychloroquine), adjuvant therapies by combining antivirals with drugs. Antibiotics or immunostimulants (vitamins C, Dm and Zinc, etc,) and several other therapies to be used depending on the region.

The Synthesis of Modified Trehalose Glycolipids: Towards Understanding Mincle and MCL Binding

<p>Trehalose glycolipids are a diverse family of long-chain fatty acid diesters isolated from the cell walls of bacteria, in particular Mycobacterium species including M. tuberculosis. These molecules possess an array of biological activities which contribute to the survival and virulence of the organism,however, it is their activity as potent stimulators of innate and early adaptive immunity for which they are of interest. In particular, trehalose glycolipids have an application as adjuvants in vaccines and immunotherapies, for diseases such as tuberculosis (TB) and cancer. Recently, the macrophage-inducible C-type lectin, Mincle, and the macrophage C-type lectin, MCL, were identified as receptors for trehalose glycolipids, however, the exact mechanisms by which these receptors recognise and bind glycolipids is, as yet, unknown.This thesis presents the synthesis of a variety of structurally diverse trehalose glycolipid analogues. As such, three mycolic acids bearing a C22 α-chain and diversified meromycolate branches were prepared from an epoxide intermediate, itself prepared in eight steps from commercially available starting materials. The mycolic acids were then coupled to TMS-trehalose and subsequently deprotected to give the mono-and diester derivatives, 1a-cand 2c, which will be assessed for their immunostimulatory activity through the activation of wild type and Mincle-/-murine macrophages. This work provides a first step towards determining how the structures of trehalose glycolipids influence Mincle and MCL binding and activity, and allow for the development of improved trehalose glycolipids for use in adjuvant therapies.</p>

The Synthesis of Modified Trehalose Glycolipids: Towards Understanding Mincle and MCL Binding

<p>Trehalose glycolipids are a diverse family of long-chain fatty acid diesters isolated from the cell walls of bacteria, in particular Mycobacterium species including M. tuberculosis. These molecules possess an array of biological activities which contribute to the survival and virulence of the organism,however, it is their activity as potent stimulators of innate and early adaptive immunity for which they are of interest. In particular, trehalose glycolipids have an application as adjuvants in vaccines and immunotherapies, for diseases such as tuberculosis (TB) and cancer. Recently, the macrophage-inducible C-type lectin, Mincle, and the macrophage C-type lectin, MCL, were identified as receptors for trehalose glycolipids, however, the exact mechanisms by which these receptors recognise and bind glycolipids is, as yet, unknown.This thesis presents the synthesis of a variety of structurally diverse trehalose glycolipid analogues. As such, three mycolic acids bearing a C22 α-chain and diversified meromycolate branches were prepared from an epoxide intermediate, itself prepared in eight steps from commercially available starting materials. The mycolic acids were then coupled to TMS-trehalose and subsequently deprotected to give the mono-and diester derivatives, 1a-cand 2c, which will be assessed for their immunostimulatory activity through the activation of wild type and Mincle-/-murine macrophages. This work provides a first step towards determining how the structures of trehalose glycolipids influence Mincle and MCL binding and activity, and allow for the development of improved trehalose glycolipids for use in adjuvant therapies.</p>

Intralesional nerve-sparing surgery versus non-surgical treatment for giant cell tumor of the sacrum

Background There is no standard treatment for giant cell tumors of the sacrum. We compared the outcomes and complications in patients with sacral giant cell tumors who underwent intralesional nerve-sparing surgery with or without (neo-) adjuvant therapies versus those who underwent non-surgical treatment (denosumab therapy and/or embolization). Methods We retrospectively investigated 15 cases of sacral giant cell tumors treated at two institutions between 2005 and 2020. Nine patients underwent intralesional nerve-sparing surgery with or without (neo-) adjuvant therapies, and six patients received non-surgical treatment. The mean follow-up period was 85 months for the surgical group (range, 25–154 months) and 59 months (range, 17–94 months) for the non-surgical group. Results The local recurrence rate was 44% in the surgical group, and the tumor progression rate was 0% in the non-surgical group. There were two surgery-related complications (infection and bladder laceration) and three denosumab-related complications (apical granuloma of the tooth, stress fracture of the sacroiliac joint, and osteonecrosis of the jaw). In the surgical group, the mean modified Biagini score (bowel, bladder, and motor function) was 0.9; in the non-surgical group, it was 0.5. None of the 11 female patients became pregnant or delivered a baby after developing a sacral giant cell tumor. Conclusions The cure rate of intralesional nerve-sparing surgery is over 50%. Non-surgical treatment has a similar risk of complications to intralesional nerve-sparing surgery and has better functional outcomes than intralesional nerve-sparing surgery, but patients must remain on therapy over time. Based on our results, the decision on the choice of treatment for sacral giant cell tumors could be discussed between the surgeon and the patient based on the tumor size and location.

Estudo do padrão de melhora da alopecia androgenética em pacientes com uso de microagulhamento associado a minoxidil e/ou plasma rico em plaquetas e mesoterapia / Study of the pattern of improvement in androgenetic alopecia in patients using microneedling associated with minoxidil and/or platelet-rich plasma and mesotherapy

Introdução: a alopécia ligada a fatores hormonais androgênicos é algo que há muito tempo tem sido alvo de estudos e aplicações de conhecimento científico em todo mundo. Este padrão de perda capilar, principalmente ligada ao sexo masculino dispõe de terapias que atualmente se limitam à interrupção da queda de fios com leve progressão de crescimento em alguns casos. Neste tocante, uma nova técnica de microagulhamento, com ou sem terapias adjuvantes, associado a métodos já consagradas como minoxidil tem levado o tratamento desta alteração estética para melhores níveis de resultado. Objetivo: conduzir uma investigação sobre os resultados atuais de pesquisas que envolvam o microagulhamento associado ao uso de Minoxidil, plasma rico em plaquetas e/ou mesoterapia. Metodologia: foram feitas pesquisas no banco de dados da PubMed e Scielo em abril de 2021 buscando-se os termos “minoxidil AND microneedling”. Resultados e Discussões: os resultados obtidos têm convergido para a proposta de que a associação do método de rolagem (microagulhamento) com a aplicação tópica do vasodilatador (minoxidil) apresenta um padrão de crescimento capilar nunca alcançado pela terapia convencional disponível, e que, se acrescentar plasma rico em plaquetas e/ou soluções através da mesoterapia, os resultados podem ser ainda mais vantajosos. Conclusão: novos estudos são necessários para abranger as vertentes ainda não elucidadas para o tratamento da alopecia, contudo, os resultados até aqui obtidos são promissores para o sucesso da reposição capilar.Palavras chave: Microagulhamento, Minoxidil, Alopecia AbstractIntroduction: alopecia linked to androgenic hormonal factors is something that has long been the subject of studies and knowledge applications worldwide. This pattern of hairloss, mainly related to males, has therapies that are currently limited to interruption of hair loss with slight growth progression in some cases. In this regard, a new microneedlingtechnique, with or without adjuvant therapies, associated with well-established methods such as minoxidil has led the treatment of this esthetic alteration to better levels of results. Objective: to conduct an investigation into the current results of research involving microneedling associated with the use of Minoxidil, platelet-rich plasma and/or mesotherapy. Methodology: searches were conducted in the PubMed and Scielo database in April 2021, searching for the terms “minoxidil AND microneedling”. Results and Discussions: the results obtained have converged to the proposal that the association of the rolling method(microneedling) with the topical application of a vasodilator (minoxidil) presents a pattern of hair growth never achieved by the available conventional therapy, and that, if addedplatelet-rich plasma and/or solutions through mesotherapy, the results can be even more advantageous. Conclusion: further studies are needed to cover aspects that have notyet been elucidated for the treatment of alopecia, however, the results obtained so far are promising for the success of hair replacement.Keywords: Microneedling, Minoxidil, Alopecia

Osteosarcoma: A review

Osteosarcoma (OS) is a type of cancer with onset in late childhood and peak at early adolescence. OS is a typically is chemo sensitive cancer. The treatment modalities include neo-adjuvant and adjuvant therapies with definitive surgery. Permutations and combinations of chemotherapeutics agents have been used. However, in many clinical trial high dose methotrexate has been used as main drug with cisplatin and doxorubicin (MAP). In recent years, case studies have cited addition of fourth drug to the three drug regimen gives a detail of drug regimen being used over past years and discusses the successful treatment.

NSCLC: Früherkennung von Rezidiven mittels zirkulierender Tumor-DNA

Approximately 30% of patients with non-small-cell lung cancer (NSCLC) present with localized/non-metastatic disease and are eligible for surgical resection or other «treatment with curative intent». Due to the high prevalence of recurrence after treatment, adjuvant therapy is standard care for most patients. The effect of adjuvant chemotherapy is, however, modest, and new tools are needed to identify candidates for adjuvant treatments (chemotherapy, immunotherapy, or targeted therapies), especially since expanded lung cancer screening programs will increase the rate of patients detected with localized NSCLC. Circulating tumor DNA (ctDNA) has shown strong potential to detect minimal residual disease (MRD) and to guide adjuvant therapies. In this manuscript, we review the technical aspects and performances of the main ctDNA sequencing platforms (TRACERx, CAPP-seq) investigated in this purpose, and discuss the potential of this approach to guide or spare adjuvant therapies after definitive treatment of NSCLC.

Metabolic Reprogramming in COVID-19

Plenty of research has revealed virus induced alternations in metabolic pathways, which is known as metabolic reprogramming. Studies focusing on COVID-19 have uncovered significant changes in metabolism, resulting in the perspective that COVID-19 is a metabolic disease. Reprogramming of amino acid, glucose, cholesterol and fatty acid is distinctive characteristic of COVID-19 infection. These metabolic changes in COVID-19 have a critical role not only in producing energy and virus constituent elements, but also in regulating immune response, offering new insights into COVID-19 pathophysiology. Remarkably, metabolic reprogramming provides great opportunities for developing novel biomarkers and therapeutic agents for COVID-19 infection. Such novel agents are expected to be effective adjuvant therapies. In this review, we integrate present studies about major metabolic reprogramming in COVID-19, as well as the possibility of targeting reprogrammed metabolism to combat virus infection.