Enhancing quality of life in severe post-COVID-19 survivors through multidisciplinary care.

Background: COVID-19 survivors who were hospitalised continue to experience long-term multisystemic sequelae and symptoms, impacting their health-related quality of life (HRQoL). The complexity of post-COVID-19 conditions underscores the importance of adopting a multidisciplinary, patient-centric approach to ensure ongoing care. This study aims to assess HRQoL and post-COVID symptoms in a cohort of severe COVID-19 survivors depending on their participation in a multidisciplinary programme. Methods: This prospective study was conducted in a post-COVID clinic staffed by a multidisciplinary team (physical rehabilitator, nutritionist, psychologist, including experts in pulmonary rehabilitation, nutrition, psychology and others). Subjects over 18 years old who were hospitalised due to severe COVID-19 during the acute phase and had attended the post-COVID clinic within the first 3 months following discharge were included. Subjects who were unable or unwilling to provide informed consent to participate in the protocol were excluded. Linear mixed-effect models were employed to examine changes in 12-Item Short-Form Health Survey (SF-12) component scores. The resolution of post-COVID symptom clusters was compared using the Cox model. Results: A total of 730 patients were included, with a mean±sd age of 55.78±15.43 years; 60.55% were male and 90.62% required mechanical ventilation during hospitalisation. Programme attendants demonstrated improved SF-12 physical and mental component scores at 3 and 12 months. A reduction in the prevalence of post-COVID symptoms was observed in both groups, with greater reductions in those attending the programme. Conclusion: Our study showed that patients enrolled on the multidisciplinary programme experienced improvements in fatigue, musculoskeletal, gastrointestinal, neuropsychiatric and respiratory symptoms, along with enhanced SF-12 mental and physical component scores.

Interrogating the precancerous evolution of pathway dysfunction in lung squamous cell carcinoma using XTABLE.

Lung squamous cell carcinoma (LUSC) is a type of lung cancer with a dismal prognosis that lacks adequate therapies and actionable targets. This disease is characterized by a sequence of low- and high-grade preinvasive stages with increasing probability of malignant progression. Increasing our knowledge about the biology of these premalignant lesions (PMLs) is necessary to design new methods of early detection and prevention, and to identify the molecular processes that are key for malignant progression. To facilitate this research, we have designed XTABLE (Exploring Transcriptomes of Bronchial Lesions), an open-source application that integrates the most extensive transcriptomic databases of PMLs published so far. With this tool, users can stratify samples using multiple parameters and interrogate PML biology in multiple manners, such as two- and multiple-group comparisons, interrogation of genes of interests, and transcriptional signatures. Using XTABLE, we have carried out a comparative study of the potential role of chromosomal instability scores as biomarkers of PML progression and mapped the onset of the most relevant LUSC pathways to the sequence of LUSC developmental stages. XTABLE will critically facilitate new research for the identification of early detection biomarkers and acquire a better understanding of the LUSC precancerous stages.

Lung squamous cell carcinoma is the second most common lung cancer. However, very little is known about how normal tissues in the lung develop in to these tumours. Like many cancers, this transformation comprises of an intermediate phase where healthy cells begin to form lesions that may (or may not) progress in to tumours. Understanding the biology of these lesions in lung squamous cell carcinoma may help clinicians detect them before they become cancerous. Knowing which genes are switched on and off during this intermediary phase can provide clues as to how these lesions form. There are already some publicly available transcriptional datasets showing the activity of tens of thousands of genes in pre-cancerous lesions extracted from patients with lung squamous cell carcinoma. But not every laboratory has the bioinformatic tools and skills required to interrogate these extensive databases. To address this, Roberts et al. built an open-source platform called XTABLE (short for Exploring Transcriptomes of Bronchial Lesions) which can analyse transcriptional datasets in multiple ways depending on the needs of the user. For instance, the tool can stratify the data into groups based on different parameters, such as the lesions potential to progress in to cancer, to see how the genes of the groups compare. It can also analyse the activity of individual genes and sets of genes involved in the same biological processes. Using XTABLE, Roberts et al. showed that a biological process linked to lung squamous cell carcinoma is also involved in the formation of pre-cancerous lesions. This suggests that molecules and genes associated with this process could potentially help scientists design prevention strategies. XTABLE will help researchers to better understand the biology of pre-cancerous lesions and how they develop in to tumours. Moreover, it will make it easier for scientists to validate their hypotheses using data collected from patients. The tool could also be useful for scientists interested in other types of lung cancers that share a similar biology.

High Flow Nasal Cannula Therapy in the Emergency Department: Main Benefits in Adults, Pediatric Population and against COVID-19: A Narrative Review.

This review aims to summarize the literature's main results about high flow nasal cannula therapy (HFNC) HFNC benefits in the Emergency Department (ED) in adults and pediatrics, including new Coronavirus Disease (COVID-19). HFNC has recently been established as the usual treatment in the ED to provide oxygen support. Its use has been generalized due to its advantages over traditional oxygen therapy devices, including decreased nasopharyngeal resistance, washing out of the nasopharyngeal dead space, generation of positive pressure, increasing alveolar recruitment, easy adaptation due to the humidification of the airways, increased fraction of inspired oxygen and improved mucociliary clearance. A wide range of pathologies has been studied to evaluate the potential benefits of HFNC; some examples are heart failure, pneumonia, chronic pulmonary obstructive disease, asthma, and bronchiolitis. The regular use of this oxygen treatment is not established yet due to the literature's controversial results. However, several authors suggest that it could be useful in several pathologies that generate acute respiratory failure. Consequently, the COVID-19 irruption has generated the question of HFNC as a safety and effective treatment. Our results suggested that HFNC seems to be a useful tool in the ED, especially in patients affected by acute hypoxemic respiratory failure, acute heart failure, pneumonia, bronchiolitis, asthma and acute respiratory distress syndrome in patients affected by COVID-19. Its benefits in hypercapnic respiratory failure are more discussed, being only observed benefits in patients with mild-moderate disease. These results are based in clinical as well as cost-effectiveness outcomes. Future studies with largest populations are required to confirm these results as well as establish a practical guideline to use this device.

Concordance between Ki-67 index in invasive breast cancer and molecular signatures: EndoPredict and MammaPrint.

Identifying patients with hormone receptor-positive (HR+) early invasive breast cancer (EIBC) who benefit from adjuvant chemotherapy has improved with molecular signature tests. However, due to high cost and limited availability, alternative tests are used. The present study sought to evaluate the performance of the proliferation marker Ki-67 to identify these patients and explore its association with molecular signatures and risk stratification markers. From the San José TecSalud Hospital in Monterrey México, patients with HR+ EIBC as tested with EndoPredict or MammaPrint and Ki-67 index were identified. They were categorized into two groups: Group 1 (June 2016-August 2018) was evaluated using EndoPredict and Group 2 (June 2016-August 2018) with MammaPrint. A ≥20% Ki67 index cutoff was utilized to identify highly proliferative EIBC and an area under the receiver-operating characteristic curve and κ concordance were utilized to evaluate the performance of Ki-67 index compared to molecular signature tests. In the EndoPredict group, 54/96 patients were considered high-risk based on their EPclin score, while 57/96 patients had Ki-67 index ≥20%. However, there was no significant overall concordance between them (59.37%, κ=0.168, P=0.09), while the given risk of distant recurrence given in percentage by EPclin had a positive association with the Ki67 index (P=0.04). In the MammaPrint group, 21/70 patients were considered high-risk and 36/70 patients presented with a Ki-67 index ≥20% with a significant overall concordance (67.14%, κ=0.35, P<0.001). In addition, high Ki-67 index was associated with the Nottingham histological grade in both groups. In conclusion, there was a concordance between Ki-67 and MammaPrint risk stratification of HR+ EIBC and no concordance with the EndoPredict molecular signature, but a positive association with the given percentage of recurrence and the median Ki-67 index as the cutoff at our center. Cost-effectiveness analyses of these tests in developing countries are required; until then, the use of Ki-67 appears reasonable to aid clinical decisions, together with the other established clinicopathological variables.

Molecular, Histological, and Clinical Characteristics of Oligodendrogliomas: A Multi-Institutional Retrospective Study.

BACKGROUND: Reports suggest that phosphatidylinositol 3-kinase pathway alterations confer increased risk of progression and poor prognosis in oligodendroglioma, IDH-mutant, and 1p/19q-codeleted molecular oligodendrogliomas (mODG). However, factors that affect prognosis in mODG have not been thoroughly studied. In addition, the benefits of adjuvant radiation and temozolomide (TMZ) in mODGs remain to be determined. OBJECTIVE: To evaluate the role of PIK3CA mutations in mODGs. METHODS: One hundred seven mODGs (2008-2019) diagnosed at 2 institutions were included. A retrospective review of clinical characteristics, molecular alterations, treatments, and outcomes was performed. RESULTS: The median age was 37 years, and 61 patients (57%) were male. There were 64 (60%) World Health Organization (WHO) grade 2 and 43 (40%) WHO grade 3 tumors. Eighty-two patients (77%) were stratified as high risk (age 40 years or older and/or subtotal resection per Radiation Treatment Oncology Group-9802). Gross-total resection was achieved in 47 patients (45%). Treatment strategies included observation (n = 15), TMZ (n = 11), radiation (n = 13), radiation/TMZ (n = 62), and others (n = 6). Our results show a benefit of TMZ vs observation in progression-free survival (PFS). No difference in PFS or overall survival (OS) was observed between radiation and radiation/TMZ. PIK3CA mutations were detected in 15 (14%) mODG, and shorter OS was observed in PIK3CA-mutant compared with PIK3CA wild-type mODGs (10.7 years vs 15.1 years, P = .009). WHO grade 3 tumors showed a shorter PFS, but no significant difference in OS was observed between WHO grades. CONCLUSION: Our findings suggest that mODGs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS with TMZ treatment, adjuvant TMZ, radiation, or a combination of the two showed no significant improvement in OS.

Antizyme Inhibitor 2-Deficient Mice Exhibit Altered Brain Polyamine Levels and Reduced Locomotor Activity.

BACKGROUND: Alterations in the neural polyamine system are known to be associated with different brain pathological conditions. In addition, the regulation of enzymes involved in polyamine metabolism such as ornithine decarboxylase (ODC), antizymes (AZs), and antizyme inhibitors (AZINs) is critical during brain development. However, while most studies focus on ODC and AZs, less is known about AZIN expression and function in the brain. Thus, our aim was to analyze the expression pattern of AZIN2 during postnatal development, its brain distribution, and its possible implication in phenotypical alterations. METHODS: The expression pattern of Azin2 and other genes related to polyamine metabolism was analyzed by RT-qPCR. ß-D-galactosidase staining was used to determine the anatomical distribution of AZIN2 in a Azin2 knockout model containing the ßGeo marker. Brain polyamine content was determined by HPLC. The Rota-Rod and Pole functional tests were used to evaluate motor skills in Azin2-lacking mice. RESULTS: Our results showed that expression of genes codifying for AZs and AZINs showed a similar increasing pattern over time that coincided with a decrease in ODC activity and putrescine levels. The analysis of AZIN2 distribution demonstrated that it is strongly expressed in the cerebellum and distributed along the neuron body and dendrites. The ablation of Azin2 showed a decrease in putrescine levels and is related to reduced motor skills. CONCLUSIONS: Our study revealed that AZIN2 expression in the brain is particularly limited to the cerebellum. In addition, the ablation of Azin2 leads to a reduction in putrescine that relates to alterations in motor function, suggesting the role of AZIN2 in the functioning of dopaminergic neurons.

Hormone exposure and its suppressive effect on risk of high-grade gliomas among patients with breast cancer.

BACKGROUND: Prior reports demonstrate the expression of estrogen and progesterone receptors in high-grade gliomas (HGGs), but the relationship between hormone receptor-positive disease and risk of HHGs in patients with breast cancer (BC) remains uncharacterized. METHODS: Using the SEER 18 registries (2000-2017), we examined the temporal trend of the incidence of HGGs and BC. The standardized incidence ratio was calculated to assess the risk of subsequent HGG in BC patients. RESULTS: During the study period, the incidence of BC and HGGs remained comparable for men and women. Among 976,134 patients with BC, we found a decreased incidence of HGGs in females, but not in males. Female BC patients with hormone receptor-positive disease were at a lower risk of developing glioblastoma and anaplastic astrocytoma. CONCLUSION: Our study findings allude to the protective role of hormone exposure in the development of HGGs, which may lead to the development of therapies targeting hormonal pathways.

Metastatic colorectal micropapillary carcinoma presenting as lymphangitic lung carcinomatosis.

Pulmonary lymphangitic carcinomatosis denotes the infiltration of tumor cells into the lung parenchymal lymphatic channels. Breast, lung, stomach, and colon adenocarcinoma are the most common origin of this invasion pattern. The micropapillary variant of colorectal adenocarcinoma has a high rate of lymph node metastases and poor overall survival. A 49 year-old man with a 6 months history of persistent cough and a relevant occupational chemical exposure had a computed tomography that showed bilateral interstitial lung infiltrates. The lung biopsy demonstrated a micropapillary adenocarcinoma with diffusely obstruction of the lung parenchymal lymphatics. The immunohistochemistry confirmed a colorectal origin. The colonoscopy evidenced a mass with identical morphology. Colorectal micropapillary carcinoma with metastatic lung lymphangitic carcinomatosis can occur, as a persistent cough, as presenting symptom in extraordinarily rare cases. To the best of our knowledge, this is the first case of an alive patient with colorectal metastatic micropapillary carcinoma presenting with lymphangitic lung carcinomatosis.

Differences in Genomic Alterations Between Brain Metastases and Primary Tumors.

BACKGROUND: Brain metastases (BMs) occur in ∼1/3 of cancer patients and are associated with poor prognosis. Genomic alterations contribute to BM development; however, mutations that predispose and promote BM development are poorly understood. OBJECTIVE: To identify differences in genomic alterations between BM and primary tumors. METHODS: A retrospective cohort of 144 BM patients were tested for genomic alterations (85 lung, 21 breast, 14 melanoma, 4 renal, 4 colon, 3 prostate, 4 others, and 9 unknown carcinomas) by a next-generation sequencing assay interrogating 315 genes. The differences in genomic alterations between BM and primary tumors from COSMIC and TCGA were evaluated by chi-square or Fisher's exact test. Overall survival curves were plotted using the Kaplan-Meier method. RESULTS: The comparison of BM and primary tumors revealed genes that were mutated in BM with increased frequency: TP53, ATR, and APC (lung adenocarcinoma); ARID1A and FGF10 (lung small-cell); PIK3CG, NOTCH3, and TET2 (lung squamous); ERBB2, BRCA2, and AXL1 (breast carcinoma); CDKN2A/B, PTEN, RUNX1T1, AXL, and FLT4 (melanoma); and ATM, AR, CDKN2A/B, TERT, and TSC1 (renal clear-cell carcinoma). Moreover, our results indicate that lung adenocarcinoma BM patients with CREBBP, GPR124, or SPTA1 mutations have a worse prognosis. Similarly, ERBB2, CDK12, or TP53 mutations are associated with worse prognosis in breast cancer BM patients. CONCLUSION: The present study demonstrates significant differences in the frequency of mutations between primary tumors and BM and identifies targetable alterations and genes that correlate with prognosis. Identifying the genomic alterations that are enriched in metastatic central nervous system tumors could help our understanding of BM development and improve patient management.