Garciaalbert1343

The COVID-19 pandemic has represented a major cause of morbidity/mortality worldwide, overstressing health systems. Multiple myeloma (MM) patients show an increased risk for infections and they are expected to be particularly vulnerable to SARS-CoV-2 infection. Here we have obtained a comprehensive picture of the impact of COVID-19 in MM patients on a local and a global scale using a federated data research network (TriNetX) that provided access to Electronic Medical Records (EMR) from Health Care Organizations (HCO) all over the world. Through propensity score matched analyses we found that the number of new diagnoses of MM was reduced in 2020 compared to 2019 (RR 0.86, 95%CI 0.76-0.96) and the survival of newly diagnosed MM cases decreased similarly (HR 0.61, 0.38-0.81). MM patients showed higher risk of SARS-CoV-2 infection (RR 2.09, 1.58-2.76) and a higher excess mortality in 2020 (difference in excess mortality 9%, 4.4-13.2) than non-MM patients. By interrogating large EMR datasets from HCO in Europe and globally, we confirmed that MM patients have been more severely impacted by COVID-19 pandemic than non-MM patients. This study highlights the necessity of extending preventive measures worlwide to protect vulnerable patients from SARS-CoV-2 infection by promoting social distancing and an intensive vaccination strategies.Genomic stability maintenance requires correct DNA replication, chromosome segregation, and DNA repair, while defects of these processes result in tumor development or cell death. Although abnormalities in DNA replication and repair regulation are proposed as underlying causes for genomic instability, the detailed mechanism remains unclear. Here, we investigated whether NKX6.3 plays a role in the maintenance of genomic stability in gastric epithelial cells. NKX6.3 functioned as a transcription factor for CDT1 and RPA1, and its depletion increased replication fork rate, and fork asymmetry. Notably, we showed that abnormal DNA replication by the depletion of NKX6.3 caused DNA damage and induced homologous recombination inhibition. Depletion of NKX6.3 also caused copy number alterations of various genes in the vast chromosomal region. Hence, our findings underscore NKX6.3 might be a crucial factor of DNA replication and repair regulation from genomic instability in gastric epithelial cells.Gene expression dysregulation in the brain has been associated with bipolar disorder, but little is known about the role of non-coding RNAs. Circular RNAs are a novel class of long noncoding RNAs that have recently been shown to be important in brain development and function. However, their potential role in psychiatric disorders, including bipolar disorder, has not been well investigated. In this study, we profiled circular RNAs in the brain tissue of individuals with bipolar disorder. Total RNA sequencing was initially performed in samples from the anterior cingulate cortex of a cohort comprised of individuals with bipolar disorder (N = 13) and neurotypical controls (N = 13) and circular RNAs were identified and analyzed using "circtools". Significant circular RNAs were validated by RT-qPCR and replicated in the anterior cingulate cortex in an independent cohort (24 bipolar disorder cases and 27 controls). In addition, we conducted in vitro studies using B-lymphoblastoid cells collected from bipolar cases (N = 19) and healthy controls (N = 12) to investigate how circular RNAs respond following lithium treatment. In the discovery RNA sequencing analysis, 26 circular RNAs were significantly differentially expressed between bipolar disorder cases and controls (FDR  less then  0.1). Of these, circCCNT2 was RT-qPCR validated showing significant upregulation in bipolar disorder (p = 0.03). This upregulation in bipolar disorder was replicated in an independent post-mortem human anterior cingulate cortex cohort and in B-lymphoblastoid cell culture. Furthermore, circCCNT2 expression was reduced in response to lithium treatment in vitro. Together, our study is the first to associate circCCNT2 to bipolar disorder and lithium treatment.The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. read more ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.Loneliness is a relatively common problem in young people (14-24 years) and predicts the onset of depression and anxiety. Interventions to reduce loneliness thus have significant potential as active ingredients in strategies to prevent or alleviate anxiety and depression among young people. Previous reviews have focused on quantitative evidence and have not examined potential mechanisms that could be targets for intervention strategies. To build on this work, in this review we aimed to combine qualitative and quantitative evidence with stakeholder views to identify interventions that appear worth testing for their potential effectiveness in reducing loneliness, anxiety and depression in young people aged 14-24 years, and provide insights into the potential mechanisms of action. We conducted a Critical Interpretative Synthesis, a systematic review method that iteratively synthesises qualitative and quantitative evidence and is explicitly focused on building theory through a critical approach to the evidence th were small or missing. Strategies to address loneliness and prevent or alleviate anxiety and depression need to be co-designed and personalised. Promising elements to incorporate into these strategies are social support, including from peers with similar experiences, and psychological therapy.BACKGROUND Amebiasis is a parasitic infection caused by the protozoan Entamoeba histolytica. Amebic brain abscesses are a rare form of invasive amebiasis frequently lethal due to the difficulty of its diagnosis and inadequate treatment. Cerebral amebiasis poses a therapeutic challenge as evidenced by the scarcity of papers reporting complete recovering after treatment. CASE REPORT We report the case of a 39-year-old Spanish man, with a history of alcohol and drug abuse. He had never traveled outside of Europe, no reported oral-anal sexual contact, and no history of immunosuppressant medication. He was admitted to the Emergency department with temperature of 38°C, abdominal pain, and diarrhea. An abdominal CT scan showed multiples abscesses in the liver. Therefore, empirical meropenem treatment was started on suspicion of pyogenic liver abscesses due to lack of epidemiological risk factors for parasitic infection. In the liver aspirate samples, E. histolytica trophozoites were directly visualized and a real-time PCR was also positive for it. After amebiasis diagnosis, intravenous (IV) metronidazole therapy was initiated. During his admission, the patient developed pulmonary, cutaneous and cerebral involvement amebiasis. The management of amebic brain abscesses includes surgical drainage and antiparasitic treatment, in our case IV metronidazole was maintained for 10 weeks. No surgical treatment was performed and even so, the patient evolved favorably. CONCLUSIONS Amebic brain abscesses have a high mortality rate if inadequate treatment. A timely diagnosis and suitable treat can reduce its mortality, so the diagnosis of amebic infection should not be precluded in non-endemic countries.BACKGROUND Left atrial spontaneous echo contrast (LASEC) is associated with an increased risk of stroke in patients with nonvalvular atrial fibrillation (NVAF). Therefore, a tool that identifies the risk of LASEC in non-anticoagulated patients with NVAF may be helpful for stroke risk stratification and early stroke prevention in these patients. The aim of this retrospective study was to establish a novel risk score model to determine the risk of ischemic stroke associated with LASEC on transesophageal echocardiography (TEE). MATERIAL AND METHODS This study retrospectively and consecutively enrolled 1255 non-anticoagulated patients with NVAF who underwent TEE prior to catheter ablation or left atrial appendage occlusion. Most importantly, a novel nomogram was developed using a logistic regression model to predict the risk of LASEC. RESULTS A nomogram was established for LASEC prediction which included 5 independent risk factors determined by multivariable logistic regression analysis increased age, non-paroxysmal atrial fibrillation, previous stroke/transient ischemic attack, congestive heart failure, and left atrial enlargement. The receiver operating characteristic curve analysis showed that the area under the curve (AUC) of the novel risk score model was 0.879 (95% confidence interval 0.849-0.909, P less then 0.001). Compared with the CHA2DS2-VASc score, the novel risk score model had a better predictive power (AUC 0.879 vs 0.617, P less then 0.001). CONCLUSIONS This novel risk score model effectively predicted the presence of LASEC in non-anticoagulated patients with NVAF.Metabolic syndrome is a long-term complication of systemic chemotherapy for testicular germ cell tumor (TGCT). It is believed to be caused by secondary hypogonadism or toxic medicines because of orchidectomy followed by systemic chemotherapy. In this study, changes in the body composition of patients over time were quantitatively analyzed up to 24 months after chemotherapy. This study retrospectively analyzed 44 patients with TGCT who underwent chemotherapy at our institution from January 2008 to December 2016. Subcutaneous and visceral fat areas and psoas and skeletal muscle areas were measured by computed tomography before and immediately after chemotherapy as well as 3 months, 6 months, 12 months, and 24 months after chemotherapy. The subcutaneous and visceral fat indices and psoas and skeletal muscle indices were calculated as each area divided by body height squared. The total fat area had already significantly increased 3 months after the initiation of chemotherapy (P = 0.004). However, it did not return to prechemotherapeutic levels even at 24 months after chemotherapy. The skeletal muscle area was significantly decreased at the end of chemotherapy (P less then 0.001); however, the value returned to baseline within 12 months. In multivariable analysis, the prechemotherapeutic skeletal muscle index and number of chemotherapy cycles were independently associated with the reduction of skeletal muscle at the end of chemotherapy (P = 0.001 and P = 0.027, respectively). In patients with TGCT, skeletal muscle mass decreased during chemotherapy and recovered within 12 months, whereas fat mass progressively increased from the initiation of chemotherapy until 24 months after chemotherapy.