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This article reviews the medico-legal aspects associated with infectious diseases, highlighting their complexity and the challenges they pose. Infectious diseases cause not only an increase in morbidity and mortality in the healthcare setting but also involve complex legal issues. Healthcare-Associated Infections (HAIs) represent a growing risk with the increase in invasive procedures and can lead to patient complications and legal claims against healthcare professionals and institutions. The consequences of medical malpractice in this context are discussed, such as diagnostic delays, inappropriate use of treatments, and lack of adequate testing, which can have serious sequelae or even result in the patient's death. The review focuses on highlighting the importance of prevention, considering that healthcare-associated infections can be difficult to avoid, posing complex legal challenges. It concludes that managing infectious diseases and their legal consequences requires careful consideration of clinical practice guidelines, prevention and control strategies, and effective communication with patients. An integrated and evidence-based approach is advocated to address these challenges, emphasizing continuous education, the use of advanced diagnostic technologies, and interdisciplinary collaboration.
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Background/Objectives: During the COVID-19 pandemic and the burden on hospital resources, the rapid categorization of high-risk COVID-19 patients became essential, and lung ultrasound (LUS) emerged as an alternative to chest computed tomography, offering speed, non-ionizing, repeatable, and bedside assessments. Various LUS score systems have been used, yet there is no consensus on an optimal severity cut-off. We assessed the performance of a 12-zone LUS score to identify adult COVID-19 patients with severe lung involvement using oxygen saturation (SpO2)/fractional inspired oxygen (FiO2) ratio as a reference standard to define the best cut-off for predicting adverse outcomes. Methods: We conducted a single-centre prospective study (August 2020-April 2021) at Hospital del Mar, Barcelona, Spain. Upon admission to the general ward or intensive care unit (ICU), clinicians performed LUS in adult patients with confirmed COVID-19 pneumonia. Severe lung involvement was defined as a SpO2/FiO2 ratio <315. The LUS score ranged from 0 to 36 based on the aeration patterns. Results: 248 patients were included. The admission LUS score showed moderate performance in identifying a SpO2/FiO2 ratio <315 (area under the ROC curve: 0.71; 95%CI 0.64-0.77). After adjustment for COVID-19 risk factors, an admission LUS score ≥17 was associated with an increased risk of in-hospital death (OR 5.31; 95%CI: 1.38-20.4), ICU admission (OR 3.50; 95%CI: 1.37-8.94) and need for IMV (OR 3.31; 95%CI: 1.19-9.13). Conclusions: Although the admission LUS score had limited performance in identifying severe lung involvement, a cut-off ≥17 score was associated with an increased risk of adverse outcomes. and could play a role in the rapid categorization of COVID-19 pneumonia patients, anticipating the need for advanced care.
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The modification N6-methyladenosine (m6A) plays an important role in determining the functional output of gene expression programs. Throughout the transcriptome, the levels of m6A are tightly regulated by the opposing activities of methyltransferases and demethylases, as well as the interaction of modified transcripts with m6A-dependent RNA-binding proteins that modulate transcript stability, often referred to as writers, erasers, and readers. The enzymatic activities of both writers and erasers are tightly linked to the cellular metabolic environment, as these enzymatic reactions rely on metabolism intermediaries as cofactors. In this review, we highlight the examples of intersection between metabolism and m6A-dependent gene regulation and discuss the different contexts where this interaction plays important roles.
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Adenosina , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Regulación de la Expresión Génica , Metiltransferasas/metabolismo , Metiltransferasas/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Transcriptoma/genéticaRESUMEN
OBJECTIVE: The present case study aims at drawing attention to a very rare presentation of the sternalis muscle noticed during routine dissection, and is intended to highlight the clinical significance and usefulness of this unique muscle in reconstructive surgeries, especially of the breast. CASE REPORT: Though many morphological variants of the muscle have been reported, we came across a unique bilateral sternalis muscle during routine dissection for undergraduate medical teaching, in an 80-year-old male cadaver. The muscle originates on both sides from the external oblique aponeurosis from the fleshy belly, and after becom-ing tendinous, converges in the midline to form a common tendon at the level of the sternal angle, and then splits again into two tendons which become continuous with the ipsilateral sternocleidomastoid. CONCLUSION: Notwithstanding the fact that the presence of a sternalis can be misdiagnosed as a wide range of anterior chest wall lesions and tumors, especially with misdiag-nosis of breast masses in routine mammograms, it has great use as a muscular flap for reconstructive surgeries of the anterior chest wall, head, neck and breast.
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Cadáver , Músculo Esquelético , Humanos , Anciano de 80 o más Años , Masculino , Pared Torácica , Esternón/anomalías , DisecciónRESUMEN
People living with human immunodeficiency virus (HIV) are the individuals most affected by the current Monkeypox virus outbreak that was first announced in May 2022. Here we report Pan-pox-specific T-cell responses in a cohort of HIV-1-infected individuals after receiving the nonreplicative, attenuated smallpox vaccine JYNNEOS from Bavarian Nordic. Intradermal (i.d.) and subcutaneous (s.c.) vaccination was safe without major side effects. Dose-sparing i.d. vaccination was superior to s.c. vaccination and promoted T-cell polyfunctionality, and the expression of the gut-homing marker α4ß7 integrin on lymphocytes. HIV-1-infected individuals with CD4 T-cell counts ≤500/mm3 blood required at least a booster vaccination to exhibit efficient virus-specific T-cell responses. The magnitude of the Th1 response after this booster directly correlated with the CD4 T-cell count of the vaccinees. Further studies with a larger number of participants are warranted to confirm and expand our observations.
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Infecciones por VIH , VIH-1 , Humanos , Linfocitos T CD4-Positivos , VacunaciónRESUMEN
Introduction: Penicillin allergy labels (PAL) are common in the hospital setting and are associated with worse clinical outcomes. Desensitization can be a useful strategy for allergic patients when alternative options are suboptimal or not available. The aim was to compare clinical outcomes of patients with PAL managed with antibiotic desensitization vs. those who received alternative non-beta-lactam antibiotic treatments. Methods: A retrospective 3:1 case-control study was performed between 2015-2022. Cases were adult PAL patients with infection who required antibiotic desensitization; controls were PAL patients with infection managed with an alternative antibiotic treatment. Cases and controls were adjusted for age, sex, infection source, and critical or non-critical medical services. Results: Fifty-six patients were included: 14 in the desensitization group, 42 in the control group. Compared to the control group, desensitized PAL patients had more comorbidities, with a higher Charlson index (7.4 vs. 5; p = 0.00) and more infections caused by multidrug-resistant (MDR) pathogens (57.1% vs. 28.6%; p = 0.05). Thirty-day mortality was 14.3% in the desensitized group, 28.6% in the control group (p = 0.24). Clinical cure occurred in 71.4% cases and 54.8% controls (p = 0.22). Four control patients selected for MDR strains after alternative treatment; selection of MDR strains did not occur in desensitized patients. Five controls had antibiotic-related adverse events, including Clostridioides difficile or nephrotoxicity. No antibiotic-related adverse events were found in the study group. In multivariate analysis, no differences between groups were observed for main variables. Conclusion: Desensitization was not associated with worse clinical outcomes, despite more severe patients in this group. Our study suggests that antibiotic desensitization may be a useful Antimicrobial Stewardship tool for the management of selected PAL patients.
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Efforts are ongoing to map synaptic wiring diagrams, or connectomes, to understand the neural basis of brain function. However, chemical synapses represent only one type of functionally important neuronal connection; in particular, extrasynaptic, "wireless" signaling by neuropeptides is widespread and plays essential roles in all nervous systems. By integrating single-cell anatomical and gene-expression datasets with biochemical analysis of receptor-ligand interactions, we have generated a draft connectome of neuropeptide signaling in the C. elegans nervous system. This network is characterized by high connection density, extended signaling cascades, autocrine foci, and a decentralized topology, with a large, highly interconnected core containing three constituent communities sharing similar patterns of input connectivity. Intriguingly, several key network hubs are little-studied neurons that appear specialized for peptidergic neuromodulation. We anticipate that the C. elegans neuropeptidergic connectome will serve as a prototype to understand how networks of neuromodulatory signaling are organized.
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Conectoma , Animales , Caenorhabditis elegans/fisiología , Neuronas/fisiología , Expresión Génica , SinapsisRESUMEN
Introduction: Glioblastoma (GBM) is a highly aggressive and lethal primary brain tumor. Despite limited treatment options, the overall survival of GBM patients has shown minimal improvement over the past two decades. Factors such as delayed cancer diagnosis, tumor heterogeneity, cancer stem cell survival, infiltrative nature of GBM cells, metabolic reprogramming, and development of therapy resistance contribute to treatment failure. To address these challenges, multitargeted therapies are urgently needed for improved GBM treatment outcomes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Dysregulated miRNAs have been identified in GBM, playing roles in tumor initiation, progression, and maintenance. Among these miRNAs, miR-92b (miRNA-92b-3p) has been found to be overexpressed in various cancers, including GBM. However, the specific target genes of miR-92b and its therapeutic potential in GBM remain poorly explored. Methods: Samples encompassed T98G, U87, and A172 human GBM cell lines, GBM tumors from Puerto Rican patients, and murine tumors. In-situ hybridization (ISH) assessed miR-92b expression in patient tumors. Transient and stable transfections modified miR-92b levels in GBM cell lines. Real-time PCR gauged gene expressions. Caspase 3 and Trypan Blue assays evaluated apoptosis and viability. Bioinformatics tools (TargetScanHuman 8.0, miRDB, Diana tools, miRWalk) predicted targets. Luciferase assays and Western Blots validated miRNA-target interactions. A subcutaneous GBM Xenograft mouse model received intraperitoneal NC-OMIs or miR92b-OMIs encapsulated in liposomes, three-times per week for two weeks. Analysis utilized GraphPad Prism 8; statistical significance was assessed using 2-tailed, unpaired Student's t-test and two-way ANOVA as required. Results: This study investigated the expression of miR-92b in GBM tumors compared to normal brain tissue samples, revealing a significant upregulation. Inhibition of miR-92b using oligonucleotide microRNA inhibitors (OMIs) suppressed GBM cell growth, migration, and induced apoptosis, while ectopic expression of miR-92b yielded opposite effects. Systemic administration of liposomal-miR92b-OMIs in GBM xenograft mice resulted in reductions in tumor volume and weight. Subsequent experiments identified F-Box and WD Repeat Domain Containing 7 (FBXW7) as a direct target gene of miR-92b in GBM cells. Discussion: FBXW7 acts as a tumor suppressor gene in various cancer types, and analysis of patient data demonstrated that GBM patients with higher FBXW7 mRNA levels had significantly better overall survival compared to those with lower levels. Taken together, our findings suggest that the dysregulated expression of miR-92b in GBM contributes to tumor progression by targeting FBXW7. These results highlight the potential of miR-92b as a therapeutic target for GBM. Further exploration and development of miR-92b-targeted therapies may offer a novel approach to improve treatment outcomes in GBM patients.
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Applying to graduate school can be particularly challenging for students from historically minoritized backgrounds due to a hidden curriculum in the graduate admissions process. To address this issue, a team of volunteer STEM trainees established the Científico Latino Graduate Student Mentorship Initiative (CL-GSMI) in 2019 to support applicants from historically minoritized backgrounds. CL-GSMI is designed to improve access to critical resources, including information, mentorship, and financial support, and has assisted 443 students in applying and matriculating to graduate school. Using program evaluation data from 2020 to 2021, we highlight areas in graduate school admissions that can be improved to promote equity and inclusion.
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Curriculum , Educación de Postgrado , Humanos , Estudiantes , Grupos MinoritariosRESUMEN
BACKGROUND: HIV infection produces a chronic inflammation which leads to early aging of people living with HIV. Even though antiretroviral treatments (ART) have significantly increased HIV patient survival, an underlying chronic inflammation persists leading to HIV-related comorbidities. In this context, changes in microRNAs (miRNAs) expression may contribute to this inflammatory response. This study aims to detect differential expression of circulating miRNAs in treatment-naïve HIV-infected individuals compared to uninfected controls and evaluation of altered miRNAs after one year of ART. METHODS: Serum from patients and controls was collected at baseline and after 48-weeks on ART in HIV-treated patients. Circulating miRNAs were analysed using next generation sequencing. RESULTS: A total of 32 HIV patients and 10 controls were recruited. Of HIV+ individuals, 7 were long-term non-progressors (elite controllers), a group of HIV-infected individuals that spontaneously control the infection. Higher circulating levels of miR-21-5p, and lower levels of miR-6503-3p and miR-3135b were detected in HIV+ progressors. After one year of ART, these miRNAs remain altered. Moreover, miR-21-5p and miR-6503-3p were also altered in elite controllers compared to control group. In silico analyses showed that miR-21-5p target pathways are related to inflammation mechanisms and immune system. CONCLUSION: miR-21-5p circulating levels are involved in inflammation and oxidative stress mechanisms in HIV patients even after one year of ART or in elite controllers.
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Infecciones por VIH , MicroARNs , Humanos , MicroARNs/metabolismo , Inflamación , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
The epidemic of complaints and/or litigation, both in and out of court, for cases of alleged malpractice has increased dramatically. In Spain, claims related to plastic surgery are gaining more and more interest. Methods: The Council of Medical Associations of Catalonia database was used to analyze claims related to plastic surgery from 1986 to 2021. Results: 1039 claims (9.8% over 10,567 total claims) were studied. Both the total number of claims (P = 0.016; R2=0.16) and the number of claims for plastic surgery (P < 0.0005; R2=0.732) showed an upward trend during the period of study. In the period from 2000 to 2021, the behavior was different; while the number of total claims stabilized (P = 0.352; R2 = 0.043), plastic surgery claims continued to show a time-related tendency to increase (P < 0.0005; R2=0.484). The distribution was 50.12% out of court. Ten unique procedures accounted for 84.5% of the total number of claims. Liability was observed in 21.46% of the closed claims, with differences between civil (20.34%), criminal (6.89%), and out-of-court (25.53%) procedures. Regarding compensation amounts, out-of-court cases had an average of 33,169.44 euros paid; civil cases, 29,153.37 euros; and criminal cases, 37,186.88 euros. Conclusions: The increase in the number of cases can only be related to an increase in the activity carried out by plastic surgeons. There has been a change in Spain in terms of the most sought-after medical specialty, with plastic surgery having displaced the perennially most sought-after specialty, orthopedic surgery and traumatology.
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Background: The impact of tenofovir disoproxil fumarate (TDF) antiretroviral (ART) regimens on bone health has been characterized mostly by bone mineral density (BMD), but recently also by bone quality (BQ). The aim of this pilot study is to assess the changes in BMD and BQ after switch from TDF to tenofovir alafenamide (TAF) ART. Methods: HIV individuals receiving TDF-based ART were randomized to switch to Bictegravir-TAF-Emtricitabine or to remain in the same regimen. At baseline and 24-weeks after randomization, participants underwent bone mineral density (BMD) by DXA and BQ assessment using bone microindentation, a validated technique that measures bone tissue quality expressed as bone material strength index (BMSi). A panel of plasma bone turnover biomarkers were measured by ELISA at the same time-points. Values are expressed as median [interquartile range] and non-parametric tests were used where appropriate. Results: A total of 24 HIV individuals were included in the study, 19 of which were men (80%). Median age at baseline was 43 years (IQR 38-54). Half of individuals were allocated in the TDF group while the other half changed to TAF treatment. No differences at baseline between both groups were detected in any parameter. Non-significant changes nor in lumbar or femoral BMD at week 24 was found in any regimen. In contrast, there was an increase in BMSi in the TAF arm at 24 weeks, and thus an improvement in BQ[81.6 (79-83) to 86 (80-88) (+5.1%);p=0.041], whereas the TDF arm remained stable from 82 (76-85) at baseline to 82 (73-83);p=0.812. Hence, at week 24 there were significant differences in BQ between arms (p=0.049). A reduction in bone formation markers was found at week 24 in both regimens: N-terminal propeptide of type-1 collagen decreased a 20% (-35 - -0.6); p=0.031 with TAF and -16% (-25 - -5); p=0.032 with TDF. Also a decrease in bone resorption marker C-telopeptide with TAF was detected [-10% (-19 - -5);p=0.028] but not with TDF (p=0.232), suggesting a less metabolically active bone after switching to TAF. Conclusion: A bone quality improvement was found after switching from a TDF to a TAF based ART independently of BMD, suggesting that the bone health benefits of TAF may extend beyond BMD. Future research should be directed to confirm these findings and to identify the underlying mechanisms of ART related bone toxicity.
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Fármacos Anti-VIH , Infecciones por VIH , Masculino , Humanos , Adulto , Persona de Mediana Edad , Femenino , Tenofovir/uso terapéutico , Proyectos Piloto , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Adenina/uso terapéutico , HuesosRESUMEN
RNA-Binding Protein with Multiple Splicing (RBPMS) is a member of family proteins that bind to nascent RNA transcripts and regulate their splicing, localization, and stability. Evidence indicates that RBPMS controls the activity of transcription factors associated with cell growth and proliferation, including AP-1 and Smads. Three major RBPMS protein splice variants (RBPMSA, RBPMSB, and RBPMSC) have been described in the literature. We previously reported that reduced RBPMS levels decreased the sensitivity of ovarian cancer cells to cisplatin treatment. However, little is known about the biological role of the RBPMS splice variants in ovarian cancer cells. We performed RT-PCR and Western blots and observed that both RBPMSA and RBPMSC are reduced at the mRNA and protein levels in cisplatin resistant as compared with cisplatin sensitive ovarian cancer cells. The mRNA and protein levels of RBPMSB were not detectable in any of the ovarian cancer cells tested. To better understand the biological role of each RBPMSA and RBPMSC, we transfected these two splice variants in the A2780CP20 and OVCAR3CIS cisplatin resistant ovarian cancer cells and performed cell proliferation, cell migration, and invasion assays. Compared with control clones, a significant reduction in the number of colonies, colony size, cell migration, and invasion was observed with RBPMSA and RBPMSC overexpressed cells. Moreover, A2780CP20-RBPMSA and A2780CP20-RBPMSC clones showed reduced senescence-associated ß-galactosidase (ß-Gal)-levels when compared with control clones. A2780CP20-RBPMSA clones were more sensitive to cisplatin treatment as compared with A2780CP20-RBPMSC clones. The A2780CP20-RBPMSA and A2780CP20-RBPMSC clones subcutaneously injected into athymic nude mice formed smaller tumors as compared with A2780CP20-EV control group. Additionally, immunohistochemical analysis showed lower proliferation (Ki67) and angiogenesis (CD31) staining in tissue sections of A2780CP20-RBPMSA and A2780CP20-RBPMSC tumors compared with controls. RNAseq studies revealed many common RNA transcripts altered in A2780CP20-RBPMSA and A2780CP20-RBPMSC clones. Unique RNA transcripts deregulated by each RBPMS variant were also observed. Kaplan-Meier (KM) plotter database information identified clinically relevant RBPMSA and RBPMSC downstream effectors. These studies suggest that increased levels of RBPMSA and RBPMSC reduce cell proliferation in ovarian cancer cells. However, only RBPMSA expression levels were associated with the sensitivity of ovarian cancer cells to cisplatin treatment.
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Antineoplásicos , Neoplasias Ováricas , Humanos , Ratones , Femenino , Animales , Ratones Desnudos , Línea Celular Tumoral , Neoplasias Ováricas/patología , Proliferación Celular/genética , Cisplatino/uso terapéutico , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Resistencia a Antineoplásicos/genética , Antineoplásicos/farmacologíaRESUMEN
Homeobox genes are prominent regulators of neuronal identity, but the extent to which their function has been probed in animal nervous systems remains limited. In the nematode Caenorhabditis elegans, each individual neuron class is defined by the expression of unique combinations of homeobox genes, prompting the question of whether each neuron class indeed requires a homeobox gene for its proper identity specification. We present here progress in addressing this question by extending previous mutant analysis of homeobox gene family members and describing multiple examples of homeobox gene function in different parts of the C. elegans nervous system. To probe homeobox function, we make use of a number of reporter gene tools, including a novel multicolor reporter transgene, NeuroPAL, which permits simultaneous monitoring of the execution of multiple differentiation programs throughout the entire nervous system. Using these tools, we add to the previous characterization of homeobox gene function by identifying neuronal differentiation defects for 14 homeobox genes in 24 distinct neuron classes that are mostly unrelated by location, function and lineage history. 12 of these 24 neuron classes had no homeobox gene function ascribed to them before, while in the other 12 neuron classes, we extend the combinatorial code of transcription factors required for specifying terminal differentiation programs. Furthermore, we demonstrate that in a particular lineage, homeotic identity transformations occur upon loss of a homeobox gene and we show that these transformations are the result of changes in homeobox codes. Combining the present with past analyses, 113 of the 118 neuron classes of C. elegans are now known to require a homeobox gene for proper execution of terminal differentiation programs. Such broad deployment indicates that homeobox function in neuronal identity specification may be an ancestral feature of animal nervous systems.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Diferenciación Celular/genética , Proteínas de Unión al ADN/genética , Empleo , Regulación del Desarrollo de la Expresión Génica , Genes Homeobox/genética , Neuronas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Individuals infected with the human immunodeficiency virus type 1 (HIV-1) belong to the group of people most vulnerable to SARS-CoV-2 infections and the associated disease COVID-19. Here we describe SARS-CoV-2-specific antibody and cellular immune responses in a small cohort of immunological non-responder HIV-1 patients (HIV-INRs) after receiving the COVID-19 mRNA-based BioNTech/Pfizer vaccine. Compared to the control group of vaccinated healthy individuals that all developed a virus-specific immune response, 5 of 10 vaccinated HIV-1 patients showed insufficient immune responses. The lack of response was not directly correlated with patients CD4 cell counts. Three of the five non-responders that agreed to receive a booster vaccination subsequently generated a virus-specific response. Thus, even HIV-INRs can be efficiently vaccinated against COVID-19 but may require a follow-up by virus-specific immune monitoring to guarantee clinical vaccine benefits.
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COVID-19 , Infecciones por VIH , Vacunas Virales , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunidad , ARN Mensajero/genética , SARS-CoV-2 , VacunaciónRESUMEN
Despite initial responses to first-line treatment with platinum and taxane-based combination chemotherapy, most high-grade serous ovarian carcinoma (HGSOC) patients will relapse and eventually develop a cisplatin-resistant fatal disease. Due to the lethality of this disease, there is an urgent need to develop improved targeted therapies against HGSOC. Herein, we identified CASC10, a long noncoding RNA upregulated in cisplatin-resistant ovarian cancer cells and ovarian cancer patients. We performed RNA sequencing (RNA-seq) in total RNA isolated from the HGSOC cell lines OVCAR3 and OV-90 and their cisplatin-resistant counterparts. Thousands of RNA transcripts were differentially abundant in cisplatin-sensitive vs. cisplatin-resistant HGSOC cells. Further data filtering unveiled CASC10 as one of the top RNA transcripts significantly increased in cisplatin-resistant compared with cisplatin-sensitive cells. Thus, we focused our studies on CASC10, a gene not previously studied in ovarian cancer. SiRNA-mediated CASC10 knockdown significantly reduced cell proliferation and invasion; and sensitized cells to cisplatin treatment. SiRNA-mediated CASC10 knockdown also induced apoptosis, cell cycle arrest, and altered the expression of several CASC10 downstream effectors. Multiple injections of liposomal CASC10-siRNA reduced tumor growth and metastasis in an ovarian cancer mouse model. Our results demonstrated that CASC10 levels mediate the susceptibility of HGSOC cells to cisplatin treatment. Thus, combining siRNA-mediated CASC10 knockdown with cisplatin may represent a plausible therapeutic strategy against HGSOC.
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Antineoplásicos , Neoplasias Ováricas , ARN Largo no Codificante , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Línea Celular Tumoral , Cisplatino/metabolismo , Cisplatino/farmacología , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos , Femenino , Humanos , Ratones , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/uso terapéutico , ARN Interferente Pequeño/farmacología , Regulación hacia Arriba/genéticaRESUMEN
Background: CD4/CD8 ratio has been used as a quantitative prognostic risk factor in patients with viral infections. This study aims to assess the association between in-hospital mortality and at admission CD4/CD8 ratio among individuals with acute SARS-CoV-2 infection. Methods: This is a longitudinal cohort study with data of all consecutive patients admitted to the COVID-19 unit at Hospital del Mar, Barcelona, Spain for ≥48 h between March to May 2020. The CD4+ CD8+ T-cell subset differentiation was assessed by flow cytometry at admission as well as a complete blood test. Patients were classified according to CD4/CD8 ratio tertiles. The primary outcome was in-hospital mortality and the secondary outcome was acute respiratory distress (ARDS). Results: A total of 338 patients were included in the cohort. A high CD4/CD8 ratio (third tertile) was associated with a higher in-hospital mortality [adjusted Cox model hazard ratio (HR) 4.68 (95%CI 1.56-14.04, p = 0.006), reference: second tertile HR 1]. Similarly, a high CD4/CD8 ratio (third tertile) was associated with a higher incidence of ARDS [adjusted logistic regression model OR 1.97 (95%CI 1.11-3.55, p = 0.022) reference: second tertile HR 1]. There was a trend of higher in-hospital mortality and incidence of ARDS in patients within the first tertile of CD4/CD8 ratio compared with the second one, but the difference was not significant. No associations were found with total lymphocyte count or inflammatory parameters, including D-dimer. Conclusion: CD4/CD8 ratio is a prognostic factor for the severity of COVID-19, reflecting the negative impact on prognosis of those individuals whose immune response has abnormal CD8+ T-cell expansion during the early response to the infection.
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Introduction. Long-term non-progressors (LTNPs) are HIV-infected individuals (HIV+) whose viral replication is controlled. However, these individuals experience complications associated with HIV, among them, bone remodeling impairment. This study aims to perform a comprehensive bone health assessment and its association with the inflammatory status of HIV+ LTNPs. A cross-sectional study was conducted comparing bone strength components (bone mineral density and bone tissue quality) between age-, sex-, and comorbidities-matched groups of HIV+ LTNPs, HIV+ progressors, and HIV-negative individuals. A panel of bone turnover and inflammatory biomarkers was measured in fasting plasma using ELISA. Bone tissue quality was assessed by bone microindentation, a technique that directly measures the bone resistance to fracture and yields a dimensionless quantifiable parameter called bone material strength (BMSi). Thirty patients were included: ten LTNPs, ten HIV+ progressors, and ten HIV-negative individuals. LTNPs showed an abnormal pattern of immune activation that was represented by significantly lower levels of anti-inflammatory cytokine IL-10 (p = 0.03), pro-inflammatory cytokine IL-8 (p = 0.01), and TNF-α (p < 0.001) with respect to the other groups. Regarding bone health, LTNPs presented lower BMSi, and thus, worse bone tissue quality than HIV-negative individuals (83 (78−85) vs. 90 (89−93), respectively; p = 0.003), and also lower BMSi than HIV+ progressors (83 (78−85) vs. 86 (85−89), respectively; p = 0.022). A trend was found of lower BMSi in HIV+ progressors with respect to the HIV-negative individuals (86 (85−89) vs. 90 (89−93), respectively; p = 0.083). No differences were detected in bone mineral density between groups. In conclusion, LTNPs showed a different inflammatory profile, along with worse bone tissue quality, when compared to HIV+ progressors and HIV-negative individuals. This may contribute to increasing evidence that HIV infection itself has a deleterious effect on bone tissue, likely through a persistent altered inflammation status.
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One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Circulating miRNAs in patients who underwent ARDS and needed mechanical ventilation (MV+; n = 15) were analyzed by next generation sequencing in comparison with patients who had COVID-19 poor symptoms but without intensive care unit requirement (MV-; n = 13). A comprehensive in silico analysis by integration with public gene expression dataset and pathway enrichment was performed. Whole miRNA sequencing identified 170 differentially expressed miRNAs between patient groups. After the validation step by qPCR in an independent sample set (MV+ = 10 vs. MV- = 10), the miR-369-3p was found significantly decreased in MV+ patients (Fold change - 2.7). After integrating with gene expression results from COVID-19 patients, the most significant GO enriched pathways were acute inflammatory response, regulation of transmembrane receptor protein Ser/Thr, fat cell differentiation, and regulation of biomineralization and ossification. In conclusion, miR-369-3p was altered in patients with mechanical ventilation requirement in comparison with COVID-19 patients without this requirement. This miRNA is involved in inflammatory response which it can be considered as a prognosis factor for ARDS in COVID-19 patients.