ABSTRACT
182 Figure 1Cardiovascular events in COVID-19 Survivors by LGE Status[Figure omitted. See PDF] 182 Figure 2All-cause mortality in COVID-19 Survivors by LGE Status[Figure omitted. See PDF]Conflict of InterestNone
ABSTRACT
BackgroundAnti-MDA5 antibody positive dermatomyositis (MDA5-DM) is characterized by high mortality due to rapid progressive ILD. MDA5 is a cytosolic protein and a family of RIG-I like receptor, which functions as a virus RNA sensor and induces the production of such as type-1 IFN. Although little is known about the pathogenesis of MDA5-DM, it is notable that the similarities were reported between COVID-19 infection and MDA5-DM. It may suggest that there is a common underlying autoinflammatory mechanism. We reported that in MDA5-DM, (1) RIG-I-like receptor signaling is enhanced and (2) antiviral responses such as type 1 IFN signaling are also enhanced as compare with anti-ARS-antibody positive DM, and (3) the key for survival is suppression of RIG-I-like and IFN signaling (EULAR2022, POS0390). We also found that a significant role for uncontrolled macrophage in the pathogenesis of ILD by our autopsy case. Recently, it has been reported that tacrolimus (TAC) and cyclophosphamide (CY) combination therapy (TC-Tx) has improved the prognosis of cases with early onset of the disease, but there are cases that cannot be saved. Therefore, we devised BRT therapy (BRT-Tx). The Tx combines baricitinib (BAR), which inhibits GM-CSF and IFN-mediated signaling and effectively suppresses uncontrolled macrophages, with rituximab (RTX) and TAC, which rapidly inhibits B and T cell interaction and ultimately prevents anti-MDA5 antibody production.ObjectivesTo determine the differences in gene expression between BRT and TC-Tx for MDA5-DM in peripheral blood.MethodsTotal of 6 MDA5-DM (TC: 3, BRT: 3) were included and all of them had multiple poor prognostic factors. Peripheral whole blood was collected at just before and 2-3 months after the treatment. RNA was extracted, and quantified using a next-generation sequencer. Differentially Expressed Genes (DEGs) were identified by pre vs. post treatment. Gene Ontology (GO), clustering and Gene Set Variation Analysis (GSVA) were performed to DEGs. As one BRT case was added since our last year's report, we also reanalyzed the surviving vs. fatal cases. The IFN signature was scored separately for Types 1, 2, and 3, and the changes between pre- and post-treatment were investigated.ResultsTwo of three cases with TC died during treatment, while all three cases on BRT recovered. The cluster analysis of the DEGs separated deaths from survivors, not by type of treatment. Comparing surviving and dead cases, GO analysis revealed that the immune system via immunoglobulins and B cells was significantly suppressed in surviving cases. GO analysis of DEGs in each therapeutic group showed that expression of B cell-related genes such as lymphocyte proliferation and B cell receptor signaling pathway were significantly suppressed in BRT-Tx. On the other hand, TC-Tx significantly suppressed such pathways as cell proliferation and cell surface receptor signaling, and was less specific for the target cells than BRT-Tx. The changes in IFN signature score after treatment showed an increase in type 2 and 3 IFN scores in all fatal cases and an increase in type 1 IFN score in one fatal case.ConclusionBRT-Tx significantly suppressed gene expression associated with B cells, while TC-Tx was characterized by low specificity of therapeutic targets and suppression of total cell proliferation. Comparison of surviving and dead cases revealed that the combination of RTX contributed to the success of treatment, as suppression of the immune system mediated by immunoglobulins and B cells is the key for survival. Analysis of the IFN signature revealed an increase in IFN score after treatment in fatal cases, indicating that the combination of BAR is beneficial. The superiority of BRT-Tx seems clear from the fact that all patients survived with BRT-Tx while only one/three patients survived with TC-Tx.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMoe Sakamoto: None declared, Yu Nakai: None declared, Yoshiharu Sato: None declared, Yoshinobu Koyama Speakers bureau: Abbvie, Asahikasei, Ayumi, BMS, Esai, Eli-Lilly, Mitsubishi Tanabe, Grant/research support from: Abbvie, GSK.
ABSTRACT
BackgroundAnti-MDA5 antibody-positive dermatomyositis (anti-MDA5+DM) is a rare autoimmune disease associated with a high mortality rate due to rapid-progressive interstitial lung disease (RP-ILD), particularly in East Asia[1]. MDA5, acts as a cytoplasmic sensor of viral RNA, thus activating antiviral responses including the type I interferon (IFN) signaling pathway[2]. The involvement of type 1 IFN in the pathogenesis of MDA5+DM has been proposed based on the significantly elevated expression of its downstream stimulated genes(ISG) in muscle, skin, lung, and peripheral blood[3;4]. Janus kinase inhibitor, which targets the IFN pathway, combined with glucocorticoid could improve the survival of early-stage MDA5+DM-ILD patients[5]. In clinical practice, there is still an urgent demand for sensitive biomarkers to facilitate clinical risk assessment and precise treatment.ObjectivesThis study aimed to investigate the clinical significance of interferon score, especially IFN-I score, in patients with anti-MDA5+DM.MethodsDifferent subtypes of idiopathic inflammatory myopathy, including anti-MDA5+DM(n=61), anti-MDA5-DM(n=20), antisynthetase syndrome(ASS,n=22),polymyositis(PM,n=6) and immune-mediated necrotizing myopathy(IMNM,n=9), and 58 healthy controls were enrolled.. A multiplex quantitative real-time PCR(RT-qPCR) assay using four TaqMan probes was utilized to evaluate two type I ISGs (IFI44, MX1, which are used for IFN-I score), one type II ISG (IRF1), and one housekeeping gene (HRPT1). Clinical features and disease activity index were compared between high and low IFN-I score groups in 61 anti-MDA5+DM patients. The association between laboratory findings and the predictive value of baseline IFN-I score level for mortality was analyzed.ResultsThe IFN scores were significantly higher in patients with anti-MDA5+DM than in HC (Figure 1A). The IFN-I score correlated positively with serum IFN α(r = 0.335, P =0.008), ferritin (r = 0.302, P = 0.018), and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score(r=0.426, P=0.001). Compared with patients with low IFN-I scores, patients with high IFN-I scores showed increased MYOACT score, CRP, AST, ferritin, and the percentages of plasma cells (PC%) but decreased lymphocyte count, natural killer cell count, and monocyte count. The 3-month survival rate was significantly lower in patients with IFN-I score > 4.9 than in those with IFN-I score ≤ 4.9(72.9% vs. 100%, P=0.044)(Figure 1B).ConclusionIFN score, especially IFN-I score, detected by multiplex RT-qPCR, can be a valuable biomarker for monitoring disease activity and predicting mortality in anti-MDA5+DM patients.References[1]I.E. Lundberg, M. Fujimoto, J. Vencovsky, R. Aggarwal, M. Holmqvist, L. Christopher-Stine, A.L. Mammen, and F.W. Miller, Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7 (2021) 86.[2]G. Liu, J.H. Lee, Z.M. Parker, D. Acharya, J.J. Chiang, M. van Gent, W. Riedl, M.E. Davis-Gardner, E. Wies, C. Chiang, and M.U. Gack, ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol 6 (2021) 467-478.[3]G.M. Moneta, D. Pires Marafon, E. Marasco, S. Rosina, M. Verardo, C. Fiorillo, C. Minetti, L. Bracci-Laudiero, A. Ravelli, F. De Benedetti, and R. Nicolai, Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histologic Features. Arthritis Rheumatol 71 (2019) 1011-1021.[4]Y. Ye, Z. Chen, S. Jiang, F. Jia, T. Li, X. Lu, J. Xue, X. Lian, J. Ma, P. Hao, L. Lu, S. Ye, N. Shen, C. Bao, Q. Fu, and X. Zhang, Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications. Nat Commun 13 (2022) 6458.[5]Z. Chen, X. Wang, and S. Ye, Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease. New England Journal of Medicine 381 (2019) 291-293.AcknowledgementsThis work was supported by the National Natural Science Foundation of China [81974251], and Shanghai Hospital Develop ent Center, Joint Research of New Advanced Technology Project [SHDC12018106]Disclosure of InterestsNone Declared.
ABSTRACT
ObjectiveTo assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen.DesignComparative observational study using data collected from routine care.SettingFour French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020.Participants181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care.InterventionsHydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group).Main outcome measuresThe primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting.ResultsIn the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment.ConclusionsHydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.
ABSTRACT
Background Novel-coronavirus disease-2019 (COVID-19) is currently a pandemic and public health emergency of international concern, as avowed by the World Health Organization (WHO). Ethiopia has become one of the affected countries as of March 15, 2020. Objective This study aimed to assess the knowledge, perceptions, and practices among the Jimma University medical center (JUMC) visitors in Jimma town. Methods A cross-sectional study was conducted on 247 sampled visitors, from 20–24 March 2020. Consecutive sampling was used to recruit the participants. The study tools were adapted from WHO resources. The data were analyzed using the Statistical Package for Social Sciences (SPSS) version 20.0. Descriptive statistics were used to describe the status of knowledge, perception, and practices. Logistic regression was executed to assess the predictors of dominant preventive practices. Results Of the 247 respondents, 205 (83.0%) knew the main clinical symptoms of COVID-19. 72.0% knew that older people who have chronic illnesses are at high risk of developing a severe form of COVID-19. About 95.1% knew that the COVID-19 virus spreads via respiratory droplets of infected people, while 77 (31.2%) of the respondents knew about the possibility of asymptomatic transmission. Only 15 (6.1%) knew that children and young adults had to involve preventive measures. Overall, 41.3% of the visitors had high knowledge. The majority, 170(68.8%), felt self-efficacious to controlling COVID-19. 207(83.3%) believed that COVID-19 is a stigmatized disease. Frequent hand washing (77.3%) and avoidance of shaking hands (53.8%) were the dominant practices. Knowledge status and self-efficacy (positively), older age, and unemployment (negatively) predicted hand washing and avoidance of handshaking. Conclusions The status of knowledge and desirable practices were not sufficient enough to combat this rapidly spreading virus. COVID-19 risk communication and public education efforts should focus on building an appropriate level of knowledge while enhancing the adoption of recommended self-care practices with special emphasis on high-risk audience segments.
ABSTRACT
Background: Definitive chemoradiotherapy (dCRT) is an option for patients with lung cancer who are medically inoperable or have unresectable locally advanced disease. The local recurrence rate after dCRT is 30% and the prognosis is poor. Salvage surgery, or surgical resection of recurrent disease following dCRT, is 1 therapeutic option;however, optimal therapy for locoregional recurrences or residual disease is controversial. The purpose of this study was to determine the efficacy of salvage lung resection. Methods: This was a single-centre retrospective database review. Patients eligible for the study received definitive chemotherapy, radiation therapy or both, followed by salvage pulmonary resection for local recurrence or residual disease. Patient characteristics and outcomes were examined. Results: Sixteen patients (11 male, 5 female) out of 201 who met the inclusion criteria treated between January 2017 and August 2020 were identified with a median follow-up time of 21 months (interquartile range [IQR] 8-37.5). The median patient age was 68 years. All 16 patients received radiation, 7 of whom received < 59 Gy and 9 of whom received > 59 Gy. The rationale for dCRT varied as 6 patients had disease considered to be unresectable, 5 patients were originally considered to be medically inoperable, 4 patients had a preference for nonsurgical management initially, and 1 patient pursued dCRT owing to uncertainty of surgical options because of the COVID-19 pandemic. The median time from radiotherapy to surgery was 22 months (IQR 14.25-27.5). The extent of salvage resections differed, as 5 patients had wedge resections, 4 had lobectomies, and 5 patients had > 1 lobe resected. No pneumonectomies were performed. Two resections were aborted in the operating room owing to upstaging at the time of resection. The final pathology was 9 adenocarcinomas, 5 squamous cell carcinomas, 1 adenosquamous carcinoma and 1 nonmalignant (nodular fibroblastic scarring with surrounding focal organizing pneumonia). Median procedure time was 3h 10.5 min. Adhesions were noted in 12 cases (75%). Ninety-day mortality was 0%. Overall survival at the most recent follow-up was 75% (12 patients). Conclusion: Salvage pulmonary resection after dCRT can be performed with low morbidity and mortality rates and is a good option for treatment of recurrent or residual disease after dCRT.
ABSTRACT
Editor's note: EMJ has partnered with the journals of multiple international emergency medicine societies to share from each a highlighted research study, as selected by their editors. This edition will feature an from each publication.
ABSTRACT
RESUMEN: Se aborda en este artículo la posición de la Educación Social frente a la incidencia a nivel mundial del COVID-19 en el ámbito de la inclusión sociolaboral, que ha supuesto y supone un nuevo reto global para sus profesionales. El aumento de la pobreza, el desempleo, las desigualdades y la calidad de la educación son elementos clave frente a los que actuar;como lo son también ese nuevo mundo de seres solitarios y distantes que se ha incrementado y que persiste, como nueva invisibilidad, luchando por la supervivencia, los ingresos y el trabajo, en busca de un sentido a su humanidad. Una situación de crisis planetaria frente a la que diferentes profesionales de la acción socioeducativa han reaccionado con responsabilidad y efectividad, a pesar de las dificultades, la impotencia y la incertidumbre iniciales, junto a una significativa falta de recursos. La Educación Social ha de multiplicar sus efectos, desde la coproducción de significados y de realidades, en los espacios de participación que le son habituales y con los Objetivos de Desarrollo Sostenible (ODS) como objetivos compartidos. Frente a unas perspectivas de recuperación mundial poco alentadoras y al pronóstico a medio y largo plazo de un importanteAlternate :This article addresses the position of Social Education in relation to the global impact of COVlD-19 in the field of socio-professional inclusion, which meant and still means a new global challenge for its professionals. The increase in poverty, unemployment, inequalities, and the quality of education are key elements to be tackled;as well as the new world of solitary and distant beings that has increased and persists, like a new invisibility, struggling for survival, income and work, in search of a meaning for their humanity. A situation of planetary crisis to which socio-educational professionals reacted responsibly and effectively, despite the initial difficulties, impotence and uncertainty, together with a significant lack of resources. Social Education must multiply the effects of its intervention, based on the co-production of meanings and realities, in the spaces and contexts of participation, with the Sustainable Development Goals (SDG) as shared objectives. Faced with a gloomy perspective of global recovery and the medium and long-term prognosis of a significant generational educational gap, which will directly affect the possibilities of social and labour inclusion of the young population, there is a need to promote a close education, which promotes the well-being and autonomy, active citizenship but also critical, transformative and committed to sustainable, fair and solidary societies.Alternate :RESUMO: Este artigo aborda a posiçao da Educaçao Social em relaçao ao impacto global da COVID-19 no domínio da inclusao socioprofissional, o que significou e ainda significa um novo desafio global para os seus profissionais. O aumento da pobreza, do desemprego, das desigualdades e da qualidade da educaçao sao elementos-chave a combater;assim como o novo mundo de seres solitários e distantes que aumentou e que persiste, como uma nova invisibilidade, lutando pela sobrevivencia, rendimento e trabalho, em busca de um significado para a sua humanidade. Uma situaçao de crise planetaria a qual os profissionais da açao sócio-educativa reagiram de forma responsável e eficaz, apesar das dificuldades, impotencia e incerteza iniciais, a par de uma significativa falta de recursos. A Educaçao Social deve multiplicar os efeitos da sua intervençao, a partir da co-produçao de significados e realidades, nos espaços de participaçao que lhe sao comuns e com os Objectivos do Desenvolvimento Sustentável (ODS) como objectivos partilhados. Face a uma perspectiva sombria de recuperaçao global e ao prognóstico a médio e longo prazo de um significativo fosso educativo geracional, que afectará directamente as possibilidades de inclusao social e laboral da populaçao jovem, há necessidade de promover uma educaçao presencial, próxima, que promova o bem-estar e a auton mia, a cidadania activa e que seja, como está sendo, crítica, transformadora e empenhada em sociedades sustentáveis, justas e solidárias.
ABSTRACT
Sepsis (S) can lead to systemic tissue damage, organ failure, and death. [...]early S diagnosis can have a significant impact on patienťs management and prognosis. According to Kang et al, PSEP can also be useful in determining the severity of odontogenic infection and sepsis, and when combined with existing test methods, it is expected to be better in evaluating patient prognosis. [...]according to this study, a PSEP level of 671.5 pg/ml or higher for odontogenic infection can be considered an abnormal level (16). Furthermore, the COVID-19 pandemic has imposed new difficulties and challenges;for example, the use of tele-dentistry, thus modifying the dental practitioner / patient relationship. [...]it would be useful, in dental practice, to introduce the use of markers that can assess the actual risk of sepsis during surgical dental procedures.
ABSTRACT
Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) premRNA splicing modifier approved by the EMA and MHRA for the treatment of patients aged ≥2 months, with a clinical diagnosis of Type 1, 2 or 3 spinal muscular atrophy (SMA) or 1–4 copies of SMN2.Safety data were pooled from three studies within the risdiplam clinical development programme:FIREFISH (NCT02913482) assesses safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of risdiplam in infants with Type 1 SMASUNFISH (NCT02908685) assesses safety, tolerability, PK, PD and efficacy of risdiplam in patients with Types 2/3 SMAJEWELFISH (NCT03032172) assesses safety, tolerability, PK and PD of risdiplam in patients who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®).Pooled analyses from FIREFISH, SUNFISH and JEWELFISH showed no treatment-related safety findings leading to withdrawal from risdiplam in 465 patients treated for up to 38.9 months (data-cut-offs: 14 November 2019, 15 January 2020 and 31 January 2020, respectively). The differences in adverse event profiles between Type 1 and Types 2/3 SMA populations appeared to be driven by the severity of the underlying disease. Here we will present updated pooled safety analyses for the risdiplam studies.
ABSTRACT
Molecular profiling has revolutionized the treatment of metastatic NSCLC. Uncommon mutations have been reported primarily in EGFR and BRAF genes and are frequently associated with atypical clinical presentations. Here, we present a rare case of a patient affected by BRAF exon 15 p.K601E-mutated lung cancer with synchronous peritoneal carcinomatosis. First line treatment with chemo-immunotherapy combinations provided a PFS of 8–9 months, whereas a second line treatment with BRAF and MEK inhibitors elicited a dissociated response. The latter clinical outcome suggests that these inhibitors have only partial activity against this rare mutation.
ABSTRACT
This report presents the case of a 65-year-old male diagnosed with two concomitant cancers: transitional cell carcinoma within bladder diverticulum (G3, pTa) and prostate adenocarcinoma cT2bN0M0 (Gleason 7 (3+4)). Due to specific location of the bladder cancer (within diverticulum) and the concomitant prostate adenocarcinoma, we decided to perform a single surgery to treat both diseases: 3D Laparoscopic cystoprostatectomy with pelvic lymphadenectomy and ileal conduit. Diverticulum bladder urothelial carcinoma in situ (pTisN0MxL0V0R0) and acinar prostate adenocarcinoma Gleason 7 (3+4) (pT2bN0MxL0V0R0), both with surgical negative margins, and 21 negative lymph nodes were reported in pathology. Seric PSA follow-up was undetectable 1 month after surgery. Clinical and therapeutic management of this disease are also discussed.
ABSTRACT
A separate meta-analysis of 28 studies by Heinrich and colleagues, published in March in Nature Medicine, showed an 85% higher suicide rate among patients with cancer compared with the general population, with strong correlations of risk with cancer prognosis and stage, time since diagnosis and geographic region. "Suicide is a huge problem in America, and we will most likely see a significant increase since the COVID-19 pandemic began," Nosayaba Osazuwa-Peters, PhD, BDS, MPH, CHES, member of Duke Cancer Institute and assistant professor in head and neck surgery and communication sciences and population health sciences at Duke University School of Medicine, told Healio ;HemOnc Today. Osazuwa-Peters and colleagues reported even larger differences in suicide risk based on area of residence among patients with head and neck cancer. The cross-sectional study, published last year in JAMA Otolaryngology-Head & Neck Surgery, included data from the SEL1 - https://media.proquest.com/media/hms/PFT/1/uf1BN?_a=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%2BgIBToIDA1dlYooDHENJRDoyMDIyMDYwNzEyMjczMzc0NTo3NTEyNTQ%3D&_s=9mfYeas7Ijzr6FwcjkLk0av32yU%3D
ABSTRACT
The cannonball pulmonary appearance is hematogenous dissemination of various primary tumors but rarely a Hodgkin's lymphoma, a disease that most commonly manifests with lymphadenopathy, often affecting the mediastinum and supraclavicular or cervical lymph nodes. To date, to the best of our knowledge, no case has been reported where the investigation of a cannonball pulmonary appearance led to the diagnosis of Hodgkin's lymphoma. Hence, in our case report, we attempt to highlight the uncommon presentation of this disease in a 14-year-old girl who initially presented with dyspnea before her chest x-ray revealed a cannonball pulmonary appearance, which was later linked with Hodgkin's lymphoma after performing a biopsy of her axillary node.
ABSTRACT
The COVID-19 pandemic has greatly affected populations worldwide and has posed a significant challenge to medical systems. With the constant increase in the number of severe COVID-19 infections, an essential area of research has been directed towards predicting the mortality rate of these patients, in order to make informed medical decisions about the necessary healthcare priorities. Although a large amount of research has attempted to predict the mortality rate of COVID-19 patients, the association between the mortality rate of COVID-19 patients and their underlying health conditions has been given significantly less attention. Meanwhile, patients with underlying conditions often face a worse COVID-19 prognosis. Therefore, the goal of this study was to classify the mortality rate of patients diagnosed with COVID-19, who also suffer from underlying health conditions or comorbidities. To achieve our goal, we applied machine learning (ML) models on a new publicly available dataset, not investigated by any existing literature. The dataset provides detailed information on 582 COVID-19 patients and facilitates a robust forecasting model of the mortality rate. The dataset was analysed using seven ML classifiers, namely, Bagging, J48, logistic regression (LR), random forest (RF), support vector machine (SVM), naïve Bayes (NB), and threshold selector. A comparative analysis was performed across the seven ML techniques, and their performance was assessed based on evaluation parameters including classification accuracy, true-positive rate, and false-positive rate. The best performance was demonstrated by the Bagging algorithm with an accuracy of 83.55% when using all the dataset features. The findings are intended to assist researchers and physicians in the early identification of at-risk COVID-19 patients and to make the appropriate intensive care decisions.
ABSTRACT
Simple SummaryBreast cancer is one of the most common cancers worldwide and the leading cause of cancer death in women. Screening, early diagnosis, and surgical techniques might increase patients’ survival, leading to a rise in the health-related consequences of anti-neoplastic therapies, such as cardiotoxicity following anthracycline treatments. Alongside conventional therapies, physical activity seems to reduce treatment side effects, improving quality of life either after a breast cancer diagnosis or in the early steps post-surgery. This review offers a general framework for the role of anthracycline in the physio-pathological mechanisms of cardiotoxicity and the effect of exercise on cancer treatment side effects. Moreover, we propose the type and the timing of exercise to better assist patients and reduce the pressure on the health care system in breast cancer patients undergoing anthracycline.The increase in breast cancer (BC) survival has determined a growing survivor population that seems to develop several comorbidities and, specifically, treatment-induced cardiovascular disease (CVD), especially those patients treated with anthracyclines. Indeed, it is known that these compounds act through the induction of supraphysiological production of reactive oxygen species (ROS), which appear to be central mediators of numerous direct and indirect cardiac adverse consequences. Evidence suggests that physical exercise (PE) practised before, during or after BC treatments could represent a viable non-pharmacological strategy as it increases heart tolerance against many cardiotoxic agents, and therefore improves several functional, subclinical, and clinical parameters. At molecular level, the cardioprotective effects are mainly associated with an exercise-induced increase of stress response proteins (HSP60 and HSP70) and antioxidant (SOD activity, GSH), as well as a decrease in lipid peroxidation, and pro-apoptotic proteins such as Bax, Bax-to-Bcl-2 ratio. Moreover, this protection can potentially be explained by a preservation of myosin heavy chain (MHC) isoform distribution. Despite this knowledge, it is not clear which type of exercise should be suggested in BC patient undergoing anthracycline treatment. This highlights the lack of special guidelines on how affected patients should be managed more efficiently. This review offers a general framework for the role of anthracyclines in the physio-pathological mechanisms of cardiotoxicity and the potential protective role of PE. Finally, potential exercise-based strategies are discussed on the basis of scientific findings.
ABSTRACT
In this paper, we explore the application of Chimeric Antigen Receptor (CAR) T cell therapy for the treatment of Acute Lymphocytic Leukaemia (ALL) by means of in silico experimentation, mathematical modelling through first-order Ordinary Differential Equations and nonlinear systems theory. By combining the latter with systems biology on cancer evolution we were able to establish a sufficient condition on the therapy dose to ensure complete response. The latter is illustrated across multiple numerical simulations when comparing three mathematically formulated administration protocols with one of a phase 1 dose-escalation trial on CAR-T cells for the treatment of ALL on children and young adults. Therefore, both our analytical and in silico results are consistent with real-life scenarios. Finally, our research indicates that tumour cells growth rate and the killing efficacy of the therapy are key factors in the designing of personalised strategies for cancer treatment.
ABSTRACT
Introduction Ecthyma gangrenosum (EG) is a rare cutaneous manifestation commonly associated with Pseudomonas aeruginosa infection in immunocompromised individuals. Additionally, different bacterial and fungal pathogens have also been identified. However, co-infection on EG lesions has never been reported before. Case report We present the case of a seven-year-old female Asian patient who initially was diagnosed with febrile neutropenia. Initially, on the sixth day of admission, dermatological status revealed multiple painless erythematous macules on the face and arms together with persistent fever followed by evolution to multiple black, deep-seated, and large central eschars and early identification of Pseudomonas aeruginosa in the blood culture. Further evaluation revealed the development of EG with XDR Acinetobacter baumannii and Aspergillus spp. isolated from the samples harvested intraoperatively. Conclusions Specific identification of etiological agents will serve its importance for early diagnosis, aggressive antibiotic treatment, and/or surgical intervention to improve the prognosis.