N-acetylglucosamine supplementation fails to bypass the critical acetylation of glucosamine-6-phosphate required for Toxoplasma gondii replication and invasion.

The cell surface of Toxoplasma gondii is rich in glycoconjugates which hold diverse and vital functions in the lytic cycle of this obligate intracellular parasite. Additionally, the cyst wall of bradyzoites, that shields the persistent form responsible for chronic infection from the immune system, is heavily glycosylated. Formation of glycoconjugates relies on activated sugar nucleotides, such as uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). The glucosamine-phosphate-N-acetyltransferase (GNA1) generates N-acetylglucosamine-6-phosphate critical to produce UDP-GlcNAc. Here, we demonstrate that downregulation of T. gondii GNA1 results in a severe reduction of UDP-GlcNAc and a concomitant drop in glycosylphosphatidylinositols (GPIs), leading to impairment of the parasite's ability to invade and replicate in the host cell. Surprisingly, attempts to rescue this defect through exogenous GlcNAc supplementation fail to completely restore these vital functions. In depth metabolomic analyses elucidate diverse causes underlying the failed rescue: utilization of GlcNAc is inefficient under glucose-replete conditions and fails to restore UDP-GlcNAc levels in GNA1-depleted parasites. In contrast, GlcNAc-supplementation under glucose-deplete conditions fully restores UDP-GlcNAc levels but fails to rescue the defects associated with GNA1 depletion. Our results underscore the importance of glucosamine-6-phosphate acetylation in governing T. gondii replication and invasion and highlight the potential of the evolutionary divergent GNA1 in Apicomplexa as a target for the development of much-needed new therapeutic strategies.

Activation of endogenous glucocorticoids by HSD11B1 inhibits the antitumor immune response in renal cancer.

Although immune-based therapies have revolutionized the management of cancer, novel approaches are urgently needed to improve their outcome. We investigated the role of endogenous steroids in the resistance to cancer immunotherapy, as these have strong immunomodulatory functions. Using a publicly available database, we found that the intratumoral expression of 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1), which regenerates inactive glucocorticoids into active glucocorticoids, was associated with poor clinical outcome and correlated with immunosuppressive gene signatures in patients with renal cell carcinoma (RCC). HSD11B1 was mainly expressed in tumor-infiltrating immune myeloid cells as seen by immunohistochemistry in RCC patient samples. Using peripheral blood mononuclear cells from healthy donors or immune cells isolated from the tumor of RCC patients, we showed that the pharmacological inhibition of HSD11B1 improved the response to the immune checkpoint inhibitor anti-PD-1. In a subcutaneous mouse model of renal cancer, the combination of an HSD11B1 inhibitor with anti-PD-1 treatment increased the proportion of tumor-infiltrating dendritic cells. In an intrarenal mouse tumor model, HSD11B1 inhibition increased the survival of mice treated with anti-PD-1. In addition, inhibition of HSD11B1 sensitized renal tumors in mice to immunotherapy with resiquimod, a Toll-like receptor 7 agonist. Mechanistically, we demonstrated that HSD11B1 inhibition combined with resiquimod increased T cell-mediated cytotoxicity to tumor cells by stimulating the antigen-presenting capacity of dendritic cells. In conclusion, these results support the use of HSD11B1 inhibitors to improve the outcome of immunotherapy in renal cancer and highlight the role of the endogenous glucocorticoid metabolism in the efficacy of immunotherapy.

Physical compatibility of sulbactam/durlobactam with select intravenous drugs during simulated Y-site administration.

PURPOSE: Sulbactam/durlobactam is a combination antibiotic designed to target Acinetobacter baumannii, including carbapenem-resistant and multidrug-resistant strains. The objective of this study was to determine the physical compatibility of sulbactam/durlobactam solution during simulated Y-site administration with 95 intravenous (IV) drugs. METHODS: Vials of sulbactam/durlobactam solution were diluted in 0.9% sodium chloride injection to a volume of 100 mL (the final concentration of both drugs was 15 mg/mL). All other IV drugs were reconstituted according to the manufacturer's recommendations and diluted with 0.9% sodium chloride injection to the upper range of concentrations used clinically or tested undiluted as intended for administration. Y-site conditions were simulated by mixing 5 mL of sulbactam/durlobactam with 5 mL of the tested drug solutions in a 1:1 ratio. Solutions were inspected for physical characteristics (clarity, color, and Tyndall effect), turbidity, and pH changes before admixture, immediately post admixture, and over 4 hours. Incompatibility was defined as any observed precipitation, significant color change, positive Tyndall test, or turbidity change of ≥0.5 nephelometric turbidity unit during the observation period. RESULTS: Sulbactam/durlobactam was physically compatible with 38 out of 42 antimicrobials tested (90.5%) and compatible overall with 86 of 95 drugs tested (90.5%). Incompatibility was observed with albumin, amiodarone hydrochloride, ceftaroline fosamil, ciprofloxacin, daptomycin, levofloxacin, phenytoin sodium, vecuronium, and propofol. CONCLUSION: The Y-site compatibility of sulbactam/durlobactam with 95 IV drugs was described. These compatibility data will assist pharmacists and nurses to safely coordinate administration of IV medications with sulbactam/durlobactam.

Hypoxia Induces Alterations in the Circadian Rhythm in Patients with Chronic Respiratory Diseases.

The function of the circadian cycle is to determine the natural 24 h biological rhythm, which includes physiological, metabolic, and hormonal changes that occur daily in the body. This cycle is controlled by an internal biological clock that is present in the body's tissues and helps regulate various processes such as sleeping, eating, and others. Interestingly, animal models have provided enough evidence to assume that the alteration in the circadian system leads to the appearance of numerous diseases. Alterations in breathing patterns in lung diseases can modify oxygenation and the circadian cycles; however, the response mechanisms to hypoxia and their relationship with the clock genes are not fully understood. Hypoxia is a condition in which the lack of adequate oxygenation promotes adaptation mechanisms and is related to several genes that regulate the circadian cycles, the latter because hypoxia alters the production of melatonin and brain physiology. Additionally, the lack of oxygen alters the expression of clock genes, leading to an alteration in the regularity and precision of the circadian cycle. In this sense, hypoxia is a hallmark of a wide variety of lung diseases. In the present work, we intended to review the functional repercussions of hypoxia in the presence of asthma, chronic obstructive sleep apnea, lung cancer, idiopathic pulmonary fibrosis, obstructive sleep apnea, influenza, and COVID-19 and its repercussions on the circadian cycles.

Predicting pediatric emergence delirium using data-driven machine learning applied to electronic health record dataset at a quaternary care pediatric hospital.

Objectives: Pediatric emergence delirium is an undesirable outcome that is understudied. Development of a predictive model is an initial step toward reducing its occurrence. This study aimed to apply machine learning (ML) methods to a large clinical dataset to develop a predictive model for pediatric emergence delirium. Materials and Methods: We performed a single-center retrospective cohort study using electronic health record data from February 2015 to December 2019. We built and evaluated 4 commonly used ML models for predicting emergence delirium: least absolute shrinkage and selection operator, ridge regression, random forest, and extreme gradient boosting. The primary outcome was the occurrence of emergence delirium, defined as a Watcha score of 3 or 4 recorded at any time during recovery. Results: The dataset included 54 776 encounters across 43 830 patients. The 4 ML models performed similarly with performance assessed by the area under the receiver operating characteristic curves ranging from 0.74 to 0.75. Notable variables associated with increased risk included adenoidectomy with or without tonsillectomy, decreasing age, midazolam premedication, and ondansetron administration, while intravenous induction and ketorolac were associated with reduced risk of emergence delirium. Conclusions: Four different ML models demonstrated similar performance in predicting postoperative emergence delirium using a large pediatric dataset. The prediction performance of the models draws attention to our incomplete understanding of this phenomenon based on the studied variables. The results from our modeling could serve as a first step in designing a predictive clinical decision support system, but further optimization and validation are needed. Clinical trial number and registry URL: Not applicable.

In vitro activity of imipenem/relebactam against Pseudomonas aeruginosa isolated from patients with cystic fibrosis.

Pseudomonas aeruginosa is a common multidrug-resistant pathogen in patients with cystic fibrosis (CF). The in vitro activity of imipenem/relebactam and imipenem was compared with other antipseudomonal antibiotics against 105 isolates from patients with CF from three US hospitals. Imipenem/relebactam, imipenem, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam susceptibilities were 77%, 55%, 58%, 90%, and 92%, respectively. Relebactam potentiates imipenem against CF P. aeruginosa by fourfold leading imipenem/relebactam to retain susceptibility against most isolates in this cohort.

Pachymeningeal disease: a systematic review and metanalysis.

BACKGROUND: Pachymeningeal disease (PMD) is a newly recognized pattern of brain metastasis (BrM) failure that specifically occurs following surgery with adjuvant stereotactic radiosurgery (SRS) and has unique prognostic implications relative to leptomeningeal disease (LMD). Here, we report its prevalence, prognostic implications, and associated risk factors. METHODS: A literature search was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses on PUBMED and Cochrane from January 2000 to June 2023. RESULTS: We identified 12 studies that included a total of 3992 BrM patients, 659 (16.5%) of whom developed meningeal disease (MD) following surgery plus adjuvant SRS, including either PMD or LMD. The mean prevalence of MD across studies was 20.9% (7.9-38.0%), with PMD accounting for 54.6% of this prevalence and LMD comprising the remaining 45.4%. Mean of the median overall survivals following diagnosis of PMD and LMD was 10.6 months and 3.7 months p = 0.007, respectively, a significant difference. Only 2 risk factors for PMD were reported in ≥ 2 studies and also identified as statistically significant per our meta-analysis: infratentorial location and controlled systemic disease status. CONCLUSION: While PMD has a superior prognosis to LMD, it is nevertheless a critical oncologic event associated with significant mortality and remains poorly recognized. PMD is predominantly observed in patients with controlled systemic disease status and infratentorial location. Future treatment strategies should focus on reducing surgical seeding and sterilizing surgical cavities.

The Benefits of Olive Oil for Skin Health: Study on the Effect of Hydroxytyrosol, Tyrosol, and Oleocanthal on Human Fibroblasts.

Fibroblasts contribute to maintaining tissue integrity and homeostasis and are a key cell population in wound healing. This cell population can be stimulated by some bioactive compounds such as extra virgin olive oil (EVOO) polyphenols. The aim of this study was to determine the effects of hydroxytyrosol (htyr), tyrosol (tyr), and oleocanthal (ole) phenolic compounds present in EVOO on the proliferation, migration, cell cycle, and antigenic profile of cultured human fibroblasts. CCD-1064Sk human fibroblast cells were treated for 24 h with each polyphenol at doses ranging 10-5 to 10-9 M. Cell proliferation was evaluated using the MTT spectrophotometric technique, migration capacity by culture insert assay, and cell cycle and antigenic profile with flow cytometry. Cell proliferation was significantly increased by treatment with all compounds. The highest increases followed treatments with htyr or tyr at doses of 10-5 or 10-6 M and with ole at 10-6 and 10-7 M, and these compounds and doses were used for assays of antigenic profile, cell cycle, and migration. During the first few hours after treatment, increased fibronectin and α-actin expressions and greater cell migration were observed, with no cell cycle changes. In conclusion, these in vitro results suggest that phenolic compounds in EVOO might contribute to wound healing through action on fibroblasts related to tissue regeneration.

Solitary Extramedullary Plasmacytoma of the Head and Neck: A Report of Three Cases Treated With Curative Radiotherapy and a Review of the Dose-Control Relationship.

Solitary plasmacytoma is an uncommon hematologic malignancy characterized by the monoclonal proliferation of abnormal plasma cells in the bone or extramedullary tissues and the absence of other multiple myeloma-defining clinical characteristics. Mostly, solitary extramedullary plasmacytoma (SEP) occurs in the head and neck region, also called solitary extramedullary plasmacytoma of the head and neck (SEPHN). Although the standard of care for SEPHN is not well established, either a surgical approach or localized external beam radiotherapy (EBRT) can be used as a definitive treatment. Due to the high radiosensitivity of SEPHN, EBRT has been associated with adequate therapeutic effects in the management of SEP, with the advantage of being a noninvasive modality that yields high rates of local control with a reasonable toxicity profile. We present a case series of three patients with SEPHN treated with EBRT at our institution with clinical outcomes.

Innovative Rocuronium Bromide Topical Formulation for Targeted Skin Drug Delivery: Design, Comprehensive Characterization, In Vitro 2D/3D Human Cell Culture and Permeation.

Cutaneous squamous cell carcinoma (cSCC) is the second-most common type of non-melanoma skin cancer and is linked to long-term exposure to ultraviolet (UV) radiation from the sun. Rocuronium bromide (RocBr) is an FDA-approved drug that targets p53-related protein kinase (PRPK) that inhibits the development of UV-induced cSCC. This study aimed to investigate the physicochemical properties and in vitro behavior of RocBr. Techniques such as thermal analysis, electron microscopy, spectroscopy and in vitro assays were used to characterize RocBr. A topical oil/water emulsion lotion formulation of RocBr was successfully developed and evaluated. The in vitro permeation behavior of RocBr from its lotion formulation was quantified with Strat-M® synthetic biomimetic membrane and EpiDerm™ 3D human skin tissue. Significant membrane retention of RocBr drug was evident and more retention was obtained with the lotion formulation compared with the solution. This is the first systematic and comprehensive study to report these findings.

Extended steroid profiling in H295R cells provides deeper insight into chemical-induced disturbances of steroidogenesis: Exemplified by prochloraz and anabolic steroids.

Human adrenocortical H295R cells have been validated by the OECD Test Guideline 456 to detect chemicals disrupting testosterone and 17ß-estradiol (estradiol) biosynthesis. This study evaluated a novel approach to detect disturbances of steroidogenesis in H295R cells, exemplified by prochloraz and five anabolic steroids. Steroid profiles were assessed by an untargeted LC-MS-based method, providing a relative quantification of 57 steroids annotated according to their accurate masses and retention times. Such a panel of steroids included several mineralocorticoids, glucocorticoids, progestins and adrenal androgens. The coverage of a high number of metabolites in this extended steroid profiling facilitated grouping of chemicals with similar effects and detecting subtler differences between chemicals. It allowed, for example, distinguishing between the effects of turinabol and oxymetholone, supposed to act similarly in a previous characterization including only nine adrenal steroids. Furthermore, the results revealed that product/substrate ratios can provide superior information on altered enzyme activities compared to individual metabolite levels. For example, the 17α-hydroxypregnenolone/pregnenolone ratio was found to be a more sensitive marker for detecting 17α-hydroxylase inhibition by prochloraz than the corresponding individual steroids. These results illustrate that chemical grouping and calculation of product/substrate ratios can provide valuable information on mode-of-action and help prioritizing further experimental work.

Modulation of Osteogenic Gene Expression by Human Osteoblasts Cultured in the Presence of Bisphenols BPF, BPS, or BPAF.

Bone effects attributed to bisphenols (BPs) include the inhibition of growth and differentiation. This study analyzes the effect of BPA analogs (BPS, BPF, and BPAF) on the gene expression of the osteogenic markers RUNX2, osterix (OSX), bone morphogenetic protein-2 (BMP-2), BMP-7, alkaline phosphatase (ALP), collagen-1 (COL-1), and osteocalcin (OSC). Human osteoblasts were obtained by primary culture from bone chips harvested during routine dental work in healthy volunteers and were treated with BPF, BPS, or BPAF for 24 h at doses of 10-5, 10-6, and 10-7 M. Untreated cells were used as controls. Real-time PCR was used to determine the expression of the osteogenic marker genes RUNX2, OSX, BMP-2, BMP-7, ALP, COL-1, and OSC. The expression of all studied markers was inhibited in the presence of each analog; some markers (COL-1; OSC, BMP2) were inhibited at all three doses and others only at the highest doses (10-5 and 10-6 M). Results obtained for the gene expression of osteogenic markers reveal an adverse effect of BPA analogs (BPF, BPS, and BPAF) on the physiology of human osteoblasts. The impact on ALP, COL-1, and OSC synthesis and therefore on bone matrix formation and mineralization is similar to that observed after exposure to BPA. Further research is warranted to determine the possible contribution of BP exposure to the development of bone diseases such as osteoporosis.

Logro de control metabólico temprano en adultos con diabetes mellitus tipo 2 en Perú

Objetivo: Estimar la proporción de sujetos con diabetes mellitus tipo 2 (DMT2) que alcanzan la meta terapéutica para HbA1C un año después del diagnóstico (control metabólico temprano). Métodos: Revisión retrospectiva de historias clínicas de adultos atendidos en 16 centros médicos distribuidos en nueve ciudades peruanas. Se incluyeron pacientes que recibieron un diagnóstico inicial de DMT2 y tuvieron al menos un año de seguimiento. Se consideraron las metas metabólicas definidas en los estándares ADA 2018. Resultados: Se incluyeron 457 sujetos (53,03% mujeres). Cuando fueron diagnosticados, la edad media fue de 55,75 años (DE ± 12,92), la media de HbA1C fue de 9,10% (DE ± 2,28). Hubo diagnóstico concomitante de hipertensión arterial o de dislipidemia en 27,13% y 52,40%, respectivamente. Al año de seguimiento, 57,76% de los sujetos alcanzó la meta de HbA1C ( 40 mg / dL), 24,31% para HDL-c en mujeres (>50 mg/dL), 48,24% para triglicéridos (<150 mg/dL), y 89,23% para presión arterial (<140/90 mmHg). Conclusiones: En este estudio en condiciones de la vida real, en adultos con DMT2 con un año de seguimiento, el logro de la meta de HbA1C (<7%) se alcanzó en el 58% de los pacientes. Si bien estos resultados son compatibles con los reportados en otros estudios de la región, se evidencia la oportunidad de mejorar el logro temprano de metas con el objetivo de optimizar los resultados a largo plazo.

Aim: To estimate the proportion of subjects with type 2 diabetes mellitus (T2DM) who attain therapeutic goal for HbA1C one year after diagnosis (early metabolic control). Methods: Retrospective review of medical records of adults cared for at 16 centers in nine Peruvian cities. Patients who received an initial diagnosis of T2DM and had at least one year of follow up were included. Metabolic goals were as defined by ADA 2018 standards. Results: 457 subjects were included (53,03% female). At diagnosis, mean age was 55,75 years (SD ± 12.92), mean HbA1C was 9,10% (SD ± 2,28). Concomitant hypertension or dyslipidemia were present in 27,13% and 52,40%, respectively. At one year follow up, 57,76% of subjects attained the goal for HbA1C ( 40 mg/dL), 24,31% for HDL-c in women (>50 mg/dL), 48,24% for triglycerides (<150 mg/dL), and 89,23% for blood pressure (<140/90 mmHg). Conclusions: In this real-life study of adults with T2DM with one year of follow up, metabolic control for HbA1C (<7%) was attained in 58% of subjects. While the results are compatible with those reported in other studies in the region, there is opportunity to further improve early treatment goal attainment to optimize long-term outcomes.

Digoxin Induces Human Astrocyte Reaction In Vitro.

Astrocyte reaction is a complex cellular process involving astrocytes in response to various types of CNS injury and a marker of neurotoxicity. It has been abundantly studied in rodents but relatively poorly in human cells due to limited access to the brain. Astrocytes play important roles in cerebral energy metabolism and are also key players in neuroinflammation. Astroglial metabolic and inflammatory changes have been reported with age, leading to the hypothesis that mitochondrial metabolism and inflammatory responses are interconnected. However, the relationship between energy metabolism and astrocyte reactivity in the context of neurotoxicity is not known. We hypothesized that changes in energy metabolism of astrocytes will be coupled to their activation by xenobiotics. Astrocyte reaction and associated energy metabolic changes were assessed by immunostaining, gene expression, proteomics, metabolomics, and extracellular flux analyses after 24 h of exposure of human ReN-derived astrocytes to digoxin (1-10 µM) or TNFα (30 ng/ml) used as a positive control. Strong astrocytic reaction was observed, accompanied by increased glycolysis at low concentrations of digoxin (0.1 and 0.5 µM) and after TNFα exposure, suggesting that increased glycolysis may be a common feature of reactive astrocytes, independent of the triggering molecule. In conclusion, whether astrocyte activation is triggered by cytokines or a xenobiotic, it is strongly tied to energy metabolism in human ReN-derived astrocytes. Increased glycolysis might be considered as an endpoint to detect astrocyte activation by potentially neurotoxic compounds in vitro. Finally, ReN-derived astrocytes may help to decipher mechanisms of neurotoxicity in ascertaining the ability of chemicals to directly target astrocytes.

Functional Repercussions of Hypoxia-Inducible Factor-2α in Idiopathic Pulmonary Fibrosis.

Hypoxia and hypoxia-inducible factors (HIFs) are essential in regulating several cellular processes, such as survival, differentiation, and the cell cycle; this adaptation is orchestrated in a complex way. In this review, we focused on the impact of hypoxia in the physiopathology of idiopathic pulmonary fibrosis (IPF) related to lung development, regeneration, and repair. There is robust evidence that the responses of HIF-1α and -2α differ; HIF-1α participates mainly in the acute phase of the response to hypoxia, and HIF-2α in the chronic phase. The analysis of their structure and of different studies showed a high specificity according to the tissue and the process involved. We propose that hypoxia-inducible transcription factor 2a (HIF-2α) is part of the persistent aberrant regeneration associated with developing IPF.

Effect of Hypoxia in the Transcriptomic Profile of Lung Fibroblasts from Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by exacerbated extracellular matrix deposition that disrupts oxygen exchange. Hypoxia and its transcription factors (HIF-1α and 2α) influence numerous circuits that could perpetuate fibrosis by increasing myofibroblasts differentiation and by promoting extracellular matrix accumulation. Therefore, this work aimed to elucidate the signature of hypoxia in the transcriptomic circuitry of IPF-derived fibroblasts. To determine this transcriptomic signature, a gene expression analysis with six lines of lung fibroblasts under normoxia or hypoxia was performed: three cell lines were derived from patients with IPF, and three were from healthy donors, a total of 36 replicates. We used the Clariom D platform, which allows us to evaluate a huge number of transcripts, to analyze the response to hypoxia in both controls and IPF. The control's response is greater by the number of genes and complexity. In the search for specific genes responsible for the IPF fibroblast phenotype, nineteen dysregulated genes were found in lung fibroblasts from IPF patients in hypoxia (nine upregulated and ten downregulated). In this sense, the signaling pathways revealed to be affected in the pulmonary fibroblasts of patients with IPF may represent an adaptation to chronic hypoxia.

Biological effects of the olive tree and its derivatives on the skin.

The olive tree and its derivatives are of great interest in the field of biomedicine due to their numerous health properties. The aim of the present study was to identify the effects of the use of olive products, extra virgin olive oil (EVOO) and products derived from its extraction, on the skin. Numerous studies have pointed out the protective effect of olive compounds on skin ageing, thanks to their role in the different mechanisms involved in the ageing process, such as reducing oxidative stress, increasing cell viability and decreasing histological alterations. With regard to their photoprotective effect, the olive tree and its fruit contain phenolic compounds which have a protective effect against radiation, such as low ultraviolet absorption and high antioxidant activity, acting as a protective factor against photocarcinogenesis. Similarly, the anti-tumour effects of olives have been studied at the level of the different compounds and extracts obtained from them, and their ability to selectively attack human melanoma cells has been observed. They have also shown antibacterial activity against microorganisms particularly implicated in skin infections, such as Escherichia coli, Candida albicans, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa and Proteus spp. Likewise, on healthy tissue, they have shown the ability to stimulate growth, migration and the expression of genes involved in cell differentiation, which favours the regeneration of skin wounds. According to the results included in this review, the olive tree and its derivatives could be useful in the treatment of many skin conditions.

Glucemia de ingreso asociada a mortalidad y estancia hospitalaria en un servicio multidisciplinario de un hospital nacional peruano

Objetivo: Evaluar la asociación entre glucemia de ingreso y desenlaces adversos en pacientes hospitalizados con COVID-19 en un hospital nacional peruano. Métodos: Estudio observacional tipo cohorte retrospectiva. Se revisaron historias clínicas electrónicas de pacientes hospitalizados por COVID-19 en un servicio de especialidades. Los pacientes se clasificaron según niveles de glucemia al ingreso: ≤ y >140mg/dL; el desenlace primario fue mortalidad y el secundario un compuesto que incluyó mortalidad, shock séptico, ventilación mecánica o traslado a UCI. Se evaluó la estancia hospitalaria y se realizó un subanálisis de regresión logística multivariada en pacientes diabéticos. Resultados: Se evaluaron 169 pacientes, media de edad 61 años, 64.5% varones. 71% presentaban alguna comorbilidad, siendo las más frecuentes: hipertensión arterial (34%), obesidad (30%), diabetes (26%). El 70% presentó gravedad tomográfica. La mediana de glucemia de ingreso fue 126.5mg/dL (RIC: 109-157mg/dL), uno de cada 3 presentó glucemia >140mg/dL. La tasa de mortalidad fue 9700 muertes por cada 100 000 personas-semana, con frecuencia de 21.3%. No se encontró diferencia significativa entre hiperglucemia y normoglucemia, tanto en mortalidad como desenlace compuesto. Los pacientes con hiperglucemia de ingreso presentaron mayor estancia hospitalaria que los normoglucémicos (19 días vs 13 días, p180mg/dL presentó OR de 6.42 (IC95%: 1.07-38.6), ajustado a edad y a gravedad clínica de ingreso. Conclusiones: La hiperglucemia al ingreso se asoció a mayor estancia hospitalaria, y los pacientes diabéticos con hiperglucemia >180mg/dL presentaron un riesgo 6 veces mayor de presentar desenlace adverso.

Objective: Evaluate the association between glycemia on admission and adverse outcomes in hospitalized patients with COVID19 in a Peruvian national hospital. Methods: Retrospective, observational cohort study. We collected data from electronic medical records of COVID19 patients in a medical specialties service. Patients were classified according to blood glucose levels on admission: ≤ and >140mg/dL. Primary outcome was mortality, and the secondary a composite that included mortality, septic shock, mechanical ventilation, or transfer to ICU. We also evaluated hospital stay and a multivariate logistic regression sub analysis was performed in diabetic patients. Results: 169 patients were evaluated. The mean age was 61 years, 64.5% were male. 71% had at least one comorbidity, the most frequent: arterial hypertension (34%), obesity (30%) and diabetes (26%). 70% presented tomographic gravity. Median blood glucose at admission was 126.5mg/dL (IQR: 109-157mg/dL), one of every 3 had blood glucose levels >140mg/dL. Mortality rate was 9700 deaths per 100000 person-weeks, with a frequency of 21.3%. No significant difference was found between hyperglycemia and normoglycemia, mortality and in composite outcome. Patients with hyperglycemia on admission had longer hospital stay than normoglycemic patients (19 vs 13 days, p180mg/dL presented OR of 6.42 (95% CI: 1.07-38.6) for composite outcome, adjusted for age and clinical severity at admission. Conclusions: Hyperglycemia at admission was associated with a longer hospital stay and diabetic patients with hyperglycemia >180mg/dL had a 6-fold increased risk of presenting an adverse outcome.

The current status of COVID-19 vaccines. A scoping review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new disease that has led to a worldwide pandemic, resulting in millions of deaths and a high economic burden. Here, we analyze the current status of preventive vaccines authorized by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Published clinical trials have shown the effectiveness of mRNA (BNT162b2 and Spikevax), adenovirus vector-based (Ad26.COV2.S and ChAdOx1 nCoV-19), and recombinant protein S (NVX-CoV2373) vaccines to be between 52.9% and 100%. The most-frequent adverse effects include local pain, fatigue, headache, or chills. Serious events are associated with Ad26.COV2.S and ChAdOx1 nCoV-19 vaccines.

ADAR1 Isoforms Regulate Let-7d Processing in Idiopathic Pulmonary Fibrosis.

Double-stranded RNA adenosine deaminase 1 (ADAR1) is significantly down-regulated in fibroblasts derived from Idiopathic Pulmonary Fibrosis (IPF) patients, and its overexpression restored levels of miRNA-21, PELI1, and SPRY2. There are two ADAR1 isoforms in humans, ADAR1-p110 and ADAR1-p150, generated by an alternative promoter. Let-7d is considered an essential microRNA in Pulmonary Fibrosis (PF). In silico analysis revealed COL3A1 and SMAD2, proteins involved in the development of IPF, as Let-7d targets. We analyzed the role of ADAR1-p110 and ADAR1-p150 isoforms in the regulation of Let-7d maturation and the effect of this regulation on the expression of COL3A1 and SMAD2 in IPF fibroblast. We demonstrated that differential expression and subcellular distribution of ADAR1 isoforms in fibroblasts contribute to the up-regulation of pri-miR-Let-7d and down-regulation of mature Let-7d. Induction of overexpression of ADAR1 reestablishes the expression of pri-miR-Let-7d and Let-7d in lung fibroblasts. The reduction of mature Let-7d upregulates the expression of COL3A1 and SMAD2. Thus, ADAR1 isoforms and Let-7d could have a synergistic role in IPF, which is a promising explanation in the mechanisms of fibrosis development, and the regulation of both molecules could be used as a therapeutic approach in IPF.