Short and mid-term neonatal outcomes in high-risk infants undergoing FICare: a case control study.

BACKGROUND: FICare model has been evaluated mostly on the stable preterm infant.We have scaled the model to two implementation levels(basic/advanced),making it suitable for all high-risk neonates.We report on the short- and mid-term outcomes of infants enrolled in a pilot on FICare implementation at our NICU. METHODS: During 52 months study period,families were invited to join the program if their newborns' admission required neonatal specialized care for at least 3 weeks,and trained according to the program's curricula.Following a rigorous sequential admission order,each case(FICare group:134 < 34 weeks;52 term newborns)was matched by a contemporary control(CC:134 < 34 weeks;52 term newborns)and 2 historical controls born within the 3 years prior to FICare site implementation(HC:268 < 34 weeks;104 term newborns),cared as usual RESULTS: FICare intervention started by the end of first week of postnatal life.Rates of breastfeeding during admission and at discharge,and direct breastfeeding upon discharge were higher in FICare compared to CC and HC.Duration of intermediate care hospitalization(preterm and term cohorts)and total hospital length of stay (term cohorts)were shorter in FICare group.Use of Emergency Services after discharge was also lower in the FICare group CONCLUSIONS: Short and mid-term efficacy of FICare on health outcomes and family empowerment in a broader and highly-vulnerable neonatal population supports its generalization in complex healthcare neonatal services. IMPACT STATEMENT: Scaling the FICare model to the critically ill, unstable premature and term infant is feasible and safe. The early intervention shows similar benefits in the short- and mid-term infants' outcomes in the whole spectrum of neonatal specialized care.

Efficacy and safety of chemotherapy in young patients with advanced gastroesophageal adenocarcinoma: data from the Spanish AGAMENON-SEOM registry.

BACKGROUND: Gastroesophageal adenocarcinoma in young adults (GCYA) counts for 10-15% of diagnoses. Previous studies have mainly focused on surgical outcomes in patients with resectable tumors; however, systemic therapy for advanced GCYA remains under-evaluated. This study aims to assess the efficacy-related outcomes and safety of first-line chemotherapy (CT) in younger versus older patients with advanced gastroesophageal adenocarcinoma. METHODS: Patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry treated with first-line polychemotherapy between January 2008 and October 2022 were included. We compared clinicopathological features, therapies received, efficacy-related outcomes, and toxicity between individuals aged < and ≥ 45 years. RESULTS: Out of 3386 patients, 263 (7.8%) were < 45 years. Young patients exhibited a higher proportion of females affected, lower ECOG-PS ≥ 2, fewer comorbidities, and more aggressive disease-related features, such as higher proportion of diffuse subtype, signet-ring cells, plastic linitis, grade 3, peritoneal metastases and metastatic disease at diagnosis. They received more triple-agent combinations and underwent more surgeries in metastatic setting. No significant differences were observed between groups in overall response rate (53.1% vs. 52.3% in < and ≥ 45 years, respectively, p = 0.579), progression-free survival (6.1 vs. 6.83 months, p = 0.158) and overall survival (11.07 vs. 10.81 months, p = 0.82), even after adjusting for potential confounding factors. Grade 3-4 adverse events were comparable in both groups, although toxicity leading to treatment discontinuation was more frequent in older patients. CONCLUSIONS: In the AGAMENON-SEOM registry, younger patients with GCYA exhibited more aggressive clinicopathological features, and despite receiving more aggressive treatments, similar efficacy outcomes and toxicity profiles were achieved compared to their older counterparts. In the AGAMENON-SEOM registry, GEAC in < 45 years showed more aggressive clinicopathological features and, although treated with more intense first-line CT regimens, similar efficacy outcomes and toxicity were achieved compared to older patients.

Cytokines and Pancreatic Ductal Adenocarcinoma: Exploring Their Relationship with Molecular Subtypes and Prognosis.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its poor prognosis. The current challenge remains the absence of predictive biomarkers. Cytokines are crucial factors in the pathogenesis and prognosis of PDAC. Furthermore, there is growing interest in differentiating between molecular subtypes of PDAC. The aim of our study is to evaluate the association between the analyzed cytokines and the molecular subtypes of PDAC and to determine their prognostic value. Cytokine levels were measured in 73 patients, and molecular subtypes were analyzed in 34 of these patients. Transforming Growth Factor Beta 2 (TGF-ß2) levels were independently associated with the basal-like and null subtypes. In patients with locally advanced and metastatic PDAC, elevated levels of interleukin (IL)-1α, IL-1ß, IL-6, IL-8, IL-9, and IL-15 were associated with a higher risk of progression during first-line treatment, and increased levels of IL-1ß, IL-6, IL-8, IL-9, and IL-15 were related to increased mortality. Furthermore, a significant association was observed between higher percentiles of IL-6 and IL-8 and shorter progression-free survival (PFS) during first-line treatment, and between higher percentiles of IL-8 and shorter overall survival (OS). In the multivariate analysis, only elevated levels of IL-8 were independently associated with a higher risk of progression during first-line treatment and mortality. In conclusion, the results of our study suggest that cytokine expression varies according to the molecular subtype of PDAC and that cytokines also play a relevant role in patient prognosis.

Long-Term Omalizumab in Elderly Patients with Chronic Urticaria: Is It a Safe Therapy?

BACKGROUND: Biologics have revolutionized the treatment of many diseases. In this regard, omalizumab (OMA), an anti-IgE monoclonal antibody, is the recommended therapeutic option for patients with chronic spontaneous urticaria (CSU) refractory to second-generation H1-antihistamines. Several studies confirm the efficacy and safety of the drug. However, the literature focusing on the elderly population is scarce, as this age group is often excluded from clinical trials. Therefore, the pharmacological treatment of CSU in elderly patients is a challenge that is increased by their comorbidities and consequent polypharmacy. OBJECTIVES: We describe the real-life safety profile of OMA in elderly patients (≥70 years) with CSU and chronic inducible urticaria (CIndU). We aimed to provide data for daily clinical practice in this vulnerable patient group. METHOD: A retrospective review was performed of the records of patients with CSU/CIndU from May 2003 to December 2019 in the Hospital Universitario La Paz. We describe qualitative and quantitative data according to measures of central tendency. Comparisons between qualitative and quantitative data were performed with the Mann-Whitney U test and the Fisher's test for qualitative variables. A p value <0.05 was considered statistically significant. RESULTS AND CONCLUSIONS: Eighty-nine patients were included, divided into two groups (<70 vs. ≥70 years). The overall rate of adverse events (AEs) was 48%, mainly mild. No association between age and AE was found (p = 0.789). No serious AE such as anaphylaxis was detected. CSU predominated in both groups. CIndU was less prevalent in the elderly (p = 0.017). There was no association between age and the other variables. Although the frequency of neoplasms was slightly higher in the elderly with OMA, we found no difference compared to the incidence of neoplasms in the general population. Therefore, our data suggest that OMA may be a safe treatment in elderly people with CSU/CIndU for prolonged periods of treatment, although further studies with larger samples are needed to corroborate our observations.

Prognostic Impact of Dihydropyrimidine Dehydrogenase Germline Variants in Unresectable Non-Small Cell Lung Cancer Patients Treated with Platin-Based Chemotherapy.

Platin-based chemotherapy is the standard treatment for patients with non-small cell lung cancer (NSCLC). However, resistance to this therapy is a major obstacle in successful treatment. In this study, we aimed to investigate the impact of several pharmacogenetic variants in patients with unresectable NSCLC treated with platin-based chemotherapy. Our results showed that DPYD variant carriers had significantly shorter progression-free survival and overall survival compared to DPYD wild-type patients, whereas DPD deficiency was not associated with a higher incidence of high-grade toxicity. For the first time, our study provides evidence that DPYD gene variants are associated with resistance to platin-based chemotherapy in NSCLC patients. Although further studies are needed to confirm these findings and explore the underlying mechanisms of this association, our results suggest that genetic testing of DPYD variants may be useful for identifying patients at a higher risk of platin-based chemotherapy resistance and might be helpful in guiding future personalized treatment strategies in NSCLC patients.

miR-124 as a Liquid Biopsy Prognostic Biomarker in Small Extracellular Vesicles from NSCLC Patients.

Despite advances in non-small cell lung cancer (NSCLC) research, this is still the most common cancer type that has been diagnosed up to date. microRNAs have emerged as useful clinical biomarkers in both tissue and liquid biopsy. However, there are no reliable predictive biomarkers for clinical use. We evaluated the preclinical use of seven candidate miRNAs previously identified by our group. We collected a total of 120 prospective samples from 88 NSCLC patients. miRNA levels were analyzed via qRT-PCR from tissue and blood samples. miR-124 gene target prediction was performed using RNA sequencing data from our group and interrogating data from 2952 NSCLC patients from two public databases. We found higher levels of all seven miRNAs in tissue compared to plasma samples, except for miR-124. Our findings indicate that levels of miR-124, both free-circulating and within exosomes, are increased throughout the progression of the disease, suggesting its potential as a marker of disease progression in both advanced and early stages. Our bioinformatics approach identified KPNA4 and SPOCK1 as potential miR-124 targets in NSCLC. miR-124 levels can be used to identify early-stage NSCLC patients at higher risk of relapse.

Safety of biological therapy in elderly patients with severe asthma.

OBJECTIVE: To assess the safety of biological therapy for severe T2 asthma (omalizumab, mepolizumab, benralizumab and reslizumab) under real-life conditions in elderly patients older than 70 years. METHODS: Retrospective data collection including clinical characteristics, comorbidities, treatment, disease control and adverse events (AE) of all patients with severe asthma on biological therapy older than 70 years seen in the Severe Asthma Unit of our hospital. RESULTS: Of 147 patients with severe asthma being treated with biologics, 21 patients older than 70 years were included. The median age of these patients was 76.3 years (range 71-86) and the majority were women (n = 18, 85.7%). There were 9 patients (42.9%) who experienced an AE related to biological treatment. Four (44.4%) were in treatment with omalizumab, two (22.2%) with mepolizumab, two patients (22.2%) with reslizumab and one (11.1%) with benralizumab. The median FEV1 (%) was 66%. These patients had a considerably higher body mass index (BMI). No significant differences were found for any other variable. Most of the AE reported were considered mild with the exception of one case of systemic AE (anaphylaxis) associated with omalizumab. CONCLUSION: This study indicates that the prescription of biological therapy in elderly patients with severe asthma seems to be safe. More evidence is needed in this particular population.

Analytical validation of a laboratory-development multigene pharmacogenetic assay.

OBJECTIVE: The implementation of pharmacogenetics (PGx) in clinical practice is an essential tool for personalized medicine. However, clinical laboratories must validate their procedures before being used to perform PGx studies in patients, in order to confirm that they are adequate for the intended purposes. METHODS: We designed a validation process for our in-house pharmacogenetic PCR-based method assay. RESULTS: The concordance to reference, repeatability and reproducibility was 100%. Sensitivity and specificity were 100% for the detection of variant diplotypes in CYP2C9, CYP3A5, TPMT, DPYD and UGT1A1 genes. The sensitivity was lower in the detection of CYP2C19 variants due to a limitation in the design that prevents the detection of CYP2C19 *2/*10 diplotype. CONCLUSIONS: The success of implementing clinical pharmacogenetic testing into routine clinical practice is dependent on the precision of genotyping. Limitations must be bearing in mind to guarantee the quality of PGx assays in clinical laboratory practice. We provided objective evidence that the necessary requirements in our laboratory-development assay were fulfilled.

Development of the Madrid Stroke Programme: Milestones and Changes in Stroke Trends and Mortality from 1997 to 2017.

INTRODUCTION: Stroke is a serious health problem, given it is the second leading cause of death and a major cause of disability in the European Union. Our study aimed to assess the impact of stroke care organization measures (such as the development of stroke units, implementation of a regional stroke code, and treatment with intravenous thrombolysis and mechanical thrombectomy) implemented from 1997 to 2017 on hospital admissions due to stroke and mortality attributed to stroke in the Madrid health region. METHODS: Epidemiological data were obtained from the National Statistics Institute public website. We collected data on the number of patients discharged with a diagnosis of stroke, in-hospital mortality due to stroke and the number of inhabitants in the Madrid health region each year. We calculated rates of discharges and mortality due to stroke and the number of inhabitants per SU bed, and we analysed temporal trends in in-hospital mortality due to stroke using the Daniels test in 2 separate time periods (before and after 2011). Figures representing annual changes in these data from 1997 to 2017 were elaborated, marking stroke care organizational measures in the year they were implemented to visualize their temporal relation with changes in stroke statistics. RESULTS: Hospital discharges with a diagnosis of stroke have increased from 170.3/100,000 inhabitants in 1997 to 230.23/100,000 inhabitants in 2017. However, the in-hospital mortality rate due to stroke has decreased (from 33.3 to 15.2%). A statistically significant temporal trend towards a decrease in the mortality percentage and rate was found from 1997 to 2011. CONCLUSIONS: Our study illustrates how measures such as the development of stroke units, implementation of a regional stroke code and treatment with intravenous thrombolysis coincide in time with a reduction in in-hospital mortality due to stroke.

Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study-A Randomized Clinical Trial.

Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight of <1000 g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomized to AF group and 23 to TF group. AF was based on blood urea nitrogen (BUN) concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day). No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge, nor during the intervention. Protein intake was significantly higher in the AF group (5.02 g/kg/day vs. 4.48 g/kg/day, p = 0.001). No differences were found in the lipid, carbohydrate, and energy intake; in the weight z score change between the different time points; nor in the length and head circumference growth. Both AF and TF are comparable methods of fortification and provide the appropriate growth rate in ELBW infants.

Trends in Faecal Zonulin Concentrations in Paediatric Patients with Celiac Disease at Baseline and on a Gluten-Free Diet: Exploring Correlations with Other Faecal Biomarkers.

Celiac disease (CeD) is an autoimmune condition triggered by gluten in genetically predisposed individuals, affecting all ages. Intestinal permeability (IP) is crucial in the pathogenesis of CeD and it is primarily governed by tight junctions (TJs) that uphold the intestinal barrier's integrity. The protein zonulin plays a critical role in modulating the permeability of TJs having emerged as a potential non-invasive biomarker to study IP. The importance of this study lies in providing evidence for the usefulness of a non-invasive tool in the study of IP both at baseline and in the follow-up of paediatric patients with CeD. In this single-centre prospective observational study, we explored the correlation between faecal zonulin levels and others faecal and serum biomarkers for monitoring IP in CeD within the paediatric population. We also aimed to establish reference values for faecal zonulin in the paediatric population. We found that faecal zonulin and calprotectin values are higher at the onset of CeD compared with the control population. Specifically, the zonulin levels were 347.5 ng/mL as opposed to 177.7 ng/mL in the control population (p = 0.001), while calprotectin levels were 29.8 µg/g stool compared to 13.9 µg/g stool (p = 0.029). As the duration without gluten consumption increased, a significant reduction in faecal zonulin levels was observed in patients with CeD (348.5 ng/mL vs. 157.1 ng/mL; p = 0.002), along with a decrease in the prevalence of patients with vitamin D insufficiency (88.9% vs. 77.8%). We conclude that faecal zonulin concentrations were higher in the patients with active CeD compared with healthy individuals or those following a gluten-free diet (GFD). The significant decrease in their values over the duration of the GFD suggests the potential use of zonulin as an additional tool in monitoring adherence to a GFD.

Loss-of-function of the Zinc Finger Homeobox 4 (ZFHX4) gene underlies a neurodevelopmental disorder.

8q21.11 microdeletions encompassing the gene encoding transcription factor ZFHX4, have previously been associated by us with a syndromic form of intellectual disability, hypotonia, decreased balance and hearing loss. Here, we report on 57 individuals, 52 probands and 5 affected family members, with protein truncating variants (n=36), (micro)deletions (n=20) or an inversion (n=1) affecting ZFHX4 with variable developmental delay and intellectual disability, distinctive facial characteristics, morphological abnormalities of the central nervous system, behavioral alterations, short stature, hypotonia, and occasionally cleft palate and anterior segment dysgenesis. The phenotypes associated with 8q21.11 microdeletions and ZFHX4 intragenic loss-of-function variants largely overlap, identifying ZFHX4 as the main driver for the microdeletion syndrome, although leukocyte-derived DNA shows a mild common methylation profile for (micro)deletions only. We identify ZFHX4 as a transcription factor that is increasingly expressed during human brain development and neuronal differentiation. Furthermore, ZFHX4 interacting factors identified via IP-MS in neural progenitor cells, suggest an important role for ZFHX4 in cellular and developmental pathways, especially during histone modifications, cytosolic transport and development. Additionally, using CUT&RUN, we observed that ZFHX4 binds with the promoter regions of genes with crucial roles in embryonic, neuron and axon development. Since loss-of-function variants in ZFHX4 are found with consistent dysmorphic facial features, we investigated whether the disruption of zfhx4 causes craniofacial abnormalities in zebrafish. First-generation (F0) zfhx4 crispant zebrafish, (mosaic) mutant for zfhx4 loss-of-function variants, have significantly shorter Meckel's cartilages and smaller ethmoid plates compared to control zebrafish. Furthermore, behavioral assays show a decreased movement frequency in the zfhx4 crispant zebrafish in comparison with control zebrafish larvae. Although further research is needed, our in vivo work suggests a role for zfhx4 in facial skeleton patterning, palatal development and behavior.

Evaluation of the clinical use of MGMT methylation in extracellular vesicle-based liquid biopsy as a tool for glioblastoma patient management.

Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings.

Use of point-of-care glucometers during an oral glucose tolerance test in children for prediabetes and diabetes diagnosis: a comparison study.

Objectives: Despite clinical guidelines do not recommend the use of point-of-care testing (POCT) glucometers for diagnostic purposes yet, the analytical performance is continuously improving. Thus, we evaluate the technical accuracy and clinical concordance of POCT glucometers during an oral glucose tolerance test (OGTT) in children for prediabetes and diabetes diagnosis in a comparison study. Methods: Pediatric patients with an OGTT indication who attended the Diabetes Unit between December 2020 and September 2021 were recruited for this prospective observational study. During the functional test, glycaemia was immediately measured in venous blood using two glucometers (unconnected and connected) and sent to the central laboratory. Results: The study included 98 patients. There was a high correlation between the glucometers and the central laboratory (Pearson correlation coefficient=0.912 and 0.950, for unconnected and connected glucometer, respectively). The median OGTT turnaround time (TAT) was significantly decreased (connected glucometer: 2.02 h [interquartile range, 2.00-2.07], central laboratory: 11.63 h [6.09-25.80]), with similar overall cost. The diagnostic concordance between connected glucometer and the central laboratory was 71.1 % (95 % confidence interval (CI) 61.5-79.2). The clinical decision would have been the same in the 92.8 % of the cases, but treatment would have not been indicated in 4 patients (4.1 %). Conclusions: POCT glucometers have demonstrated a high correlation and an acceptable diagnostic concordance with the central laboratory during an OGTT, as well the connected device offers a significant decrease in TAT, without increasing costs. However, as severe clinical impact could happen, POCT glucometers may not be used for diagnosis yet.

MiR-151a: a robust endogenous control for normalizing small extracellular vesicle cargo in human cancer.

Small extracellular vesicles (sEVs) in the blood of cancer patients contain higher amounts of tumor markers than those identified as free-circulating. miRNAs have significant biomedical relevance due to their high stability and feasible detection. However, there is no reliable endogenous control available to measure sEVs-miRNA content, impairing the acquisition of standardized consistent measurements in cancer liquid biopsy. In this study, we identified three miRNAs from a panel of nine potential normalizers that emerged from a comprehensive analysis comparing the sEV-miRNA profile of six lung and ovarian human cancer cell lines in the absence of or under different conditions. Their relevance as normalizers was tested in 26 additional human cancer cell lines from nine different tumor types undergoing chemotherapy or radiotherapy treatment. The validation cohorts were comprised of 242 prospective plasma and ascitic fluid samples from three different human tumor types. Variability and normalization properties were tested in comparison to miR-16, the most used control to normalize free-circulating miRNAs in plasma. Our results indicate that miR-151a is consistently represented in small extracellular vesicles with minimal variability compared to miR-16, providing a novel normalizer to measure small extracellular vesicle miRNA content that will benefit liquid biopsy in cancer patients.

Prognostic 18F-FDG Radiomic Features in Advanced High-Grade Serous Ovarian Cancer.

High-grade serous ovarian cancer (HGSOC) is an aggressive disease with different clinical outcomes and poor prognosis. This could be due to tumor heterogeneity. The 18F-FDG PET radiomic parameters permit addressing tumor heterogeneity. Nevertheless, this has been not well studied in ovarian cancer. The aim of our work was to assess the prognostic value of pretreatment 18F-FDG PET radiomic features in patients with HGSOC. A review of 36 patients diagnosed with advanced HGSOC between 2016 and 2020 in our center was performed. Radiomic features were obtained from pretreatment 18F-FDGPET. Disease-free survival (DFS) and overall survival (OS) were calculated. Optimal cutoff values with receiver operating characteristic curve/median values were used. A correlation between radiomic features and DFS/OS was made. The mean DFS was 19.6 months and OS was 37.1 months. Total Lesion Glycolysis (TLG), GLSZM_ Zone Size Non-Uniformity (GLSZM_ZSNU), and GLRLM_Run Length Non-Uniformity (GLRLM_RLNU) were significantly associated with DFS. The survival-curves analysis showed a significant difference of DSF in patients with GLRLM_RLNU > 7388.3 versus patients with lower values (19.7 months vs. 31.7 months, p = 0.035), maintaining signification in the multivariate analysis (p = 0.048). Moreover, Intensity-based Kurtosis was associated with OS (p = 0.027). Pretreatment 18F-FDG PET radiomic features GLRLM_RLNU, GLSZM_ZSNU, and Kurtosis may have prognostic value in patients with advanced HGSOC.

SARS-CoV-2 outbreak impact on a trauma unit.

BACKGROUND: From February 2020 onwards, our country has been hit by the coronavirus severe acute respiratory syndrome-2 (SARS-CoV-2) infection. At a glance, hospitals became overrun and had to reformulate all the assistance guidelines, focusing on the coronavirus disease 2019. One year after the start of the pandemic, we present the results of a morbimortality study. AIM: To analyze how our department was affected by the outbreak in terms of morbimortality, and to analyze demographic data, admission to hospital-related data, and subgroups analyses for patients with hip fractures and polytrauma. METHODS: We designed a study comparing data from patients who were admitted to our unit due to a lower limb fracture or a high energy trauma during the pandemic (from March to April 2020) to those admitted during the same period in 2019 before the pandemic. during the pandemic situation. Both cohorts completed a minimum of 6 mo of follow-up. RESULTS: The number of patients admitted to hospital in 2020 was nearly half of those in 2019. Hip fractures in the elderly represented 52 out of 73 of the admitted patients. Twenty patients had a positive test result for SARS-CoV-2 infection. Patients with SARS-CoV-2 infection were admitted to the hospital for a longer time than the non-infected (P < 0.001), and had a higher mortality rate during hospitalization and follow-up (P = 0.02). Patients with a hip fracture associated with a severe respiratory syndrome were mostly selected for conservative treatment (P = 0.03). CONCLUSION: Mortality and readmission rates were higher in the 2020 cohort and during follow-up, in comparison with the cohort in 2019.

Clinical validation of a novel quantitative assay for the detection of MGMT methylation in glioblastoma patients.

BACKGROUND: The promoter hypermethylation of the methylguanine-DNA methyltransferase gene is a frequently used biomarker in daily clinical practice as it is associated with a favorable prognosis in glioblastoma patients treated with temozolamide. Due to the absence of adequately standardized techniques, international harmonization of the MGMT methylation biomarker is still an unmet clinical need for the diagnosis and treatment of glioblastoma patients. RESULTS: In this study we carried out a clinical validation of a quantitative assay for MGMT methylation detection by comparing a novel quantitative MSP using double-probe (dp_qMSP) with the conventional MSP in 100 FFPE glioblastoma samples. We performed both technologies and established the best cutoff for the identification of positive-methylated samples using the quantitative data obtained from dp_qMSP. Kaplan-Meier curves and ROC time dependent curves were employed for the comparison of both methodologies. CONCLUSIONS: We obtained similar results using both assays in the same cohort of patients, in terms of progression free survival and overall survival according to Kaplan-Meier curves. In addition, the results of ROC(t) curves showed that dp_qMSP increases the area under curve time-dependent in comparison with MSP for predicting progression free survival and overall survival over time. We concluded that dp_qMSP is an alternative methodology compatible with the results obtained with the conventional MSP. Our assay will improve the therapeutic management of glioblastoma patients, being a more sensitive and competitive alternative methodology that ensures the standardization of the MGMT-biomarker making it reliable and suitable for clinical use.

miR-7 methylation as a biomarker to predict poor survival in early-stage non-small cell lung cancer patients.

Non-small-cell lung cancer (NSCLC) is the most common malignancy worldwide. Platinum-based chemotherapy is the standard of care for these patients. Recent research showed that miR-7 methylation status is a biomarker of cisplatin resistance in lung and ovarian cancer cells, which is one of the major limitations associated with their clinical management. The aim of the present study is to provide clinical insights associated with this novel potential biomarker in NSCLC patients by comparing the miR-7 methylation status with the cisplatin treatment response. Our results analyzed in 81 samples show that miR-7 methylation is a common event in tumor tissue and it is more frequent as the stage of the disease advances, remaining in 75% of metastatic patients. Tumor miR-7 unmethylation trend to a better PFS in early stages, and when our data was validated in an extended "in silico" cohort of 969 patients we obtained a significant increment in PFS and OS in those patients harboring miR-7 unmethylated (p = 0.010 and p = 0.007 respectively). When we select those early-stages patients harbouring miR-7 methylation, we observed that adenocarcinoma patients present a dramatic decrease in PFS compared with squamous cell carcinoma patients (median 18.9 versus 59.7 months, p = 0.002). In conclusion, our results show that presence of miR-7 methylation in early-stage NSCLC is suggestive of aggressive behavior, especially for adenocarcinoma patients. One major challenge in early diagnosis in NSCLC is identify the subgroup of patients that could benefit for adjuvant therapy, our data establish the basis for epigenetic classification on early-stage NSCLC that could influence treatment decisions in the future.