In this first analysis, samples from 23 BC survivors (group 1) and 291 healthy female controls (group 2) were characterised through the V3 and V4 regions that encode the "16S rRNA" gene of each ...bacteria. The samples were sequenced by next-generation sequencing (NGS), and the taxonomy was identified by resorting to Kraken2 and improved with Bracken, using a curated database called 'GutHealth_DB'. The α and β-diversity analyses were used to determine the richness and evenness of the gut microbiota. A non-parametric Mann-Whitney
test was applied to assess differential abundance between both groups. The Firmicutes/Bacteroidetes (F/B) ratio was calculated using a Kruskal-Wallis chi-squared test. The α-diversity was significantly higher in group 1 (
= 0.28 × 10
for the Chao index and
= 1.64 × 10
for the ACE index). The Shannon index, a marker of richness and evenness, was not statistically different between the two groups (
= 0.72). The microbiota composition was different between the two groups: a null hypothesis was rejected for PERMANOVA (
= 9.99 × 10
) and Anosim (
= 0.04) and was not rejected for β-dispersion (
= 0.158), using Unifrac weighted distance. The relative abundance of 14 phyla, 29 classes, 25 orders, 64 families, 116 genera, and 74 species differed significantly between both groups. The F/B ratio was significantly lower in group 1 than in group 2,
< 0.001. Our study allowed us to observe significant taxonomic disparities in the two groups by testing the differences between BC survivors and healthy controls. Additional studies are needed to clarify the involved mechanisms and explore the relationship between microbiota and BC survivorship.
Gut microbiota is intrinsically associated with the immune system and can promote or suppress infectious diseases, especially viral infections. This study aims to characterize and compare the ...microbiota profile of infected patients with SARS-CoV-2 (milder or severe symptoms), non-infected people, and recovered patients. This is a national, transversal, observational, multicenter, and case-control study that analyzed the microbiota of COVID-19 patients with mild or severe symptoms at home, at the hospital, or in the intensive care unit, patients already recovered, and healthy volunteers cohabiting with COVID-19 patients. DNA was isolated from stool samples and sequenced in a NGS platform. A demographic questionnaire was also applied. Statistical analysis was performed in SPSS.
Firmicutes/Bacteroidetes ratios were found to be significantly lower in infected patients (1.61 and 2.57) compared to healthy volunteers (3.23) and recovered patients (3.89). Furthermore, the microbiota composition differed significantly between healthy volunteers, mild and severe COVID-19 patients, and recovered patients. Furthermore
,
, and
were shown to be more frequent in severe cases. The most common COVID-19 symptoms were linked to certain microbiome groups.
We can conclude that microbiota composition is significantly affected by SARS-CoV-2 infection and may be used to predict COVID-19 clinical evolution. Therefore, it will be possible to better allocate healthcare resources and better tackle future pandemics.
Introduction
Cancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the ...pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer.
Methods
An anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents’ regions, case volumes, and practice type were explored.
Results
Of 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents’ region and case volume were noted.
Conclusion
Medical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown.
Plain Language Summary
This study was an online survey of Portuguese medical oncologists to determine how they managed patients with breast cancer during the COVID-19 pandemic. Forty-two questions covered topics such as how COVID testing was done, the types of cancer treatments used, and how this compared to before the pandemic. It also examined whether the geographic region, the number of patients each doctor was responsible for (caseload), and the type of medical institution influenced how patients with breast cancer were managed. One hundred and twenty-nine oncologists completed the survey, of whom 108 worked in the public health system, making this survey representative of breast cancer management during the COVID-19 pandemic across Portugal. Most (71%) said there were fewer visits for new cases of breast cancer during lockdown. The use of telemedicine increased, as did the use of pre-surgery hormone therapy or chemotherapy when access to surgery was difficult, and the use of anticancer medications taken orally or metronomically (low doses given frequently over a long time period). Chemotherapy given very frequently (dose-dense) was used less often, and fewer patients participated in clinical trials. Treatment decisions for patients with aggressive breast cancer types (e.g., triple-negative breast cancer) were largely unchanged, except for greater use of cyclin-dependent kinase 4/6 inhibitors—drugs targeting the cell cycle and cell division control. Geographic region and caseload influenced treatment decisions. All of these changes in breast cancer treatment during the COVID-19 pandemic were logical and reasonable for the circumstances, but their long-term impact is not yet known.
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. The mainstay of management for GBM is surgical resection, radiation (RT), and chemotherapy (CT). Even with ...optimized multimodal treatment, GBM has a high recurrence and poor survival rates ranging from 12 to 24 months in most patients. Recently, relevant advances in understanding GBM pathophysiology have opened new avenues for therapies for recurrent and newly diagnosed diseases. GBM's hypoxic microenvironment has been shown to be highly associated with aggressive biology and resistance to RT and CT. Hyperbaric oxygen therapy (HBOT) may increase anticancer therapy sensitivity by increasing oxygen tension within the hypoxic regions of the neoplastic tissue. Previous data have investigated HBOT in combination with cytostatic compounds, with an improvement of neoplastic tissue oxygenation, inhibition of HIF-1α activity, and a significant reduction in the proliferation of GBM cells. The biological effect of ionizing radiation has been reported to be higher when it is delivered under well-oxygenated rather than anoxic conditions. Several hypoxia-targeting strategies reported that HBOT showed the most significant effect that could potentially improve RT outcomes, with higher response rates and survival and no serious adverse events. However, further prospective and randomized studies are necessary to validate HBOT's effectiveness in the ‘real world' GBM clinical practice.
Kienböck’s disease is a rare condition characterised by avascular necrosis of the lunate bone. Its natural history and aetiopathogenesis have not yet been clarified, nor are its triggering factors ...identified. We present a case of a 17-year-old male gymnast, without relevant medical/family history, with stage IIIA Kienböck’s disease diagnosed in 2016. Initially, submitted to conservative treatment that proved to be insufficient. Consequently, surgical treatment was proposed, but refused. The patient instead underwent experimental treatment with hyperbaric oxygen (120 sessions, 100% oxygen at 2.5 atm, for 70 min periods, once daily, five times per week). In April 2018, a favourable clinical and radiological evolution was observed, with an improvement in the patterns of pain, motion and strength and an almost complete involution of the process of aseptic necrosis of the semilunar. To the best of our knowledge, this is the first report of Kienböck’s disease treated with hyperbaric oxygen.
Pneumatosis cystoides intestinalis (PCI) is characterized by gas-filled cysts within gastrointestinal tract wall from esophagus to rectum, with preferential involvement of large and small intestine. ...PCI is rare with an estimated incidence of 0.03 to 0-2% in general population. PCI can be distinguished into idiopathic (15%) or secondary (85%) and the clinical picture ranges from completely asymptomatic to life-threatening intraabdominal complications. Although etiology of PCI appears to be multifactorial, the exact pathophysiology is poorly understood and two main theories have been proposed (mechanical and bacterial). Over the last decades, an enormous therapeutic armamentarium was considered in PCI's management, including hyperbaric oxygen therapy (HBOT). Treatment comprises conservative treatment in mild cases to surgery in highly symptomatic and complicated PCI. In the late 70s, HBOT started to be used in selected cases of PCI not responding to conservative measures. Since then, several case reports, case series, and reviews have been published in the literature with variable outcomes. The overall response rate and complete response were 92.1% (
= 82/89) and 65.2% (
= 58/89), respectively, with a median follow-up of 7 months. Furthermore, HBOT is extremely safe, with few reported complications in the literature when used for PCI. Nevertheless, a randomized, controlled, and double-blind clinical trial is unlikely to occur given the rarity of PCI, logistical issues of HBOT, and methodological considerations related to adequate blinding with a sham-controlled group. HBOT in combination with personalized diet and antibiotics may be beneficial for moderate to severe PCI in patients with no indication for emergency exploratory laparotomy. The purpose of this article is to synthesize the existing data, analyse results of previous studies, identify gaps in knowledge, and discuss PCI' management, including the proposal of an algorithm, with a special focus on HBOT.
intestinal-type sinonasal adenocarcinoma (ITAC) is a rare epithelium tumor of the nasal cavities and paranasal sinuses. Exposure to wood and leather dusts is a strong etiological factor related to ...its development. Prolonged cork exposure has rarely been associated.
thirty-seven-year (1981-2018) retrospective cohort analysis of all consecutive patients with sinonasal cancer (SNC) followed at our institution. Medical records were reviewed to determine patient demographics, occupational/environmental exposure, location and extent of the tumor, stage, histopathology findings, treatment strategies, and oncologic outcomes. Survival analysis was done using Kaplan-Meier method.
we evaluated 379 patients with SNC, including 39 (10.3%) ITAC. Patient median age was 73 years (range 49-87), 56% male and 69% with identified professional occupational exposure (54% for cork; 69.2% considering only those for which an agent has been identified). Seventy-two percent had locally advanced disease (stage III or IVA-B). The initial treatment was surgery in 77%, and 54% received adjuvant radiotherapy. The median time to progression, progression-free survival, and overall-survival was 2.36 years (95% CI 1.54-8.70), 1.96 years (95% CI 1.43-3.74), and 3.51 years (95% CI 2.33-10.02), respectively.
ITAC is an uncommon malignancy that grows silently, which contributes to delayed diagnosis, advanced stage and low survival rates. In our cohort, we observed a high prevalence of cork occupational exposure. This finding may lead to the implementation of protection measures and suggest a potential link to be further studied.
BackgroundNovel combination therapies are needed to improve outcomes in RM-HNSCC. Magrolimab is a monoclonal antibody that blocks CD47, a ‘don’t eat me’ signal overexpressed on cancer cells. ...Magrolimab induces macrophage-mediated phagocytosis of tumor cells and may synergize with chemotherapy agents through enhancement of phagocytic signals. The Phase 2 ELEVATE HNSCC multicenter, open-label study (NCT04854499) is evaluating magrolimab-containing regimens in patients with RM-HNSCC (figure 1). Here, we report data from 2 safety run-ins (SRI1 and SRI2) designed to assess safety/tolerability and recommended Phase 2 dose (RP2D) of magrolimab in combination with standard of care.MethodsPatients in SRI1 with previously untreated RM-HNSCC received magrolimab+pembrolizumab+platinum+5-fluorouracil; patients in SRI2 with locally advanced or RM-HNSCC (1–2 lines of prior systemic therapy) received magrolimab+docetaxel. Magrolimab was first administered as a 1 mg/kg priming dose, followed by weekly 30 mg/kg doses for two 21-day cycles and then a maintenance dose of 60 mg/kg Q3W. Pembrolizumab and chemotherapy were given per standard of care. Primary endpoints of the SRI were incidence of adverse events (AEs) and dose-limiting toxicities (DLTs). Safety was assessed in patients who received ≥1 dose of study drug. The incidence of DLTs was assessed using patients who experienced a DLT during the DLT evaluation period or who completed ≥2 magrolimab and ≥1 combination agent doses. To select an RP2D, ≤2 of 6 DLT-evaluable patients could experience a DLT, or the magrolimab dose would be de-escalated and a new cohort would be assessed.ResultsAt least 6 patients from each SRI were considered DLT-evaluable. The safety analysis population consisted of 6 patients in SRI1 and 7 patients in SRI2. No DLTs were reported. Treatment-emergent AEs (TEAEs) occurred in 6/6 (SRI1) and 7/7 (SRI2) patients (table 1). The most common TEAEs observed in each SRI were fatigue (SRI1) and anemia (SRI2). TEAEs leading to magrolimab discontinuation occurred in 1/6 patients in SRI1 (fatigue) and 1/7 patients in SRI2 (oral cavity fistula unrelated to study drug). In SRI1, no deaths were reported; 3 deaths were reported as unrelated to study treatment and occurred after the DLT evaluation period in SRI2: oral cavity fistula, pneumonia, and disease progression (during long-term follow-up).ConclusionsThe observed safety profile was as expected based on the known toxicity profiles of the individual agents. Magrolimab appears tolerable in these combinations. No DLTs or treatment-related deaths occurred. Magrolimab RP2D was declared at the initial dose level tested in both SRIs.Trial RegistrationNCT04854499Ethics ApprovalThe protocol and proposed informed consent form were reviewed and approved by all relevant Institutional Review Boards, Independent Ethics Committees and/or Research Ethics Boards prior to study commencement. There is no number provided as we did not receive one. Participants gave informed consent to participate in the study before taking part.ConsentThe protocol and proposed informed consent form were reviewed and approved by all relevant Institutional Review Boards, Independent Ethics Committees and/or Research Ethics Boards prior to study commencement. There is no number provided as we did not receive one. Participants gave informed consent to participate in the study before taking part.Abstract 675 Figure 1ELEVATE HNSCC cohort overview. 5-FU. 5-fluorouracil; HNSCC, head and neck squamous cell carcinoma; R, ranomization; RP2D, recommended Phase 2 dose; pembro, pembrolizumab; zim, zimberelimabAbstract 675 Table 1TEAEs occurring in ≥2 patients in either SRI.
Resumo Introdução: O pé diabético é uma complicação frequente da diabetes mellitus com importante repercussão a nível clínico, psicossocial e económico, exigindo dos prestadores de cuidados de saúde ...uma abordagem terapêutica multimodal. Definiu-se como objetivo principal a revisão da literatura sobre o tratamento complementar do pé diabético com oxigenoterapia hiperbárica e as suas perspetivas futuras no tratamento desta complicação. Material e métodos: Pesquisa bibliográfica através da PubMed, CINAHL, Cochrane e Google Académico desde 2014, utilizando os seguintes descritores: pé diabético, úlcera diabética e oxigenoterapia hiperbárica. Foram analisadas trinta e duas publicações, tendo sido selecionados seis artigos de revisão. Resultados: A oxigenoterapia hiperbárica parece eficaz na cicatrização aos seis meses, promissora na cicatrização de lesões com mais de doze meses de evolução e associada a uma baixa incidência de efeitos adversos. A saturação de oxigénio transcutânea foi maior e houve menor incidência de amputação major dos membros inferiores no subgrupo de doentes tratados com esta terapia. Discussão: A evidência atual aponta para um benefício clínico da oxigenoterapia hiperbárica enquanto modalidade terapêutica complementar do pé diabético. Ainda não é totalmente conhecido o perfil clínico ideal do doente que beneficiará deste tipo de tratamento pelas heterogeneidades e limitações metodológicas dos estudos considerados. É importante a realização de mais ensaios clínicos prospetivos, aleatorizados e controlados que consubstanciem a sua eficácia.
PDF
