Influence of diabetes and other risk factors on in-hospital mortality following kidney transplantation: an analysis of the Spanish National Hospital Discharge Database from 2016 to 2020.

INTRODUCTION: To assess time trends in incidence, clinical characteristics, complications, and hospital outcomes among patients with type 1 diabetes (T1D), with type 2 diabetes (T2D), and patients without diabetes who underwent kidney transplant (KT); to identify variables associated with in-hospital mortality (IHM); and to determine the impact of the COVID-19 pandemic. RESEARCH DESIGN AND METHODS: We used a nationwide discharge database to select KT recipients admitted to Spanish hospitals from 2016 to 2020. We stratified patients according to diabetes status. We used multivariable logistic regression to identify the variables associated with IHM. RESULTS: A total of 14 594 KTs were performed in Spain (T2D, 22.28%; T1D, 3.72%). The number of KTs rose between 2016 and 2019 and and decreased from 2019 to 2020 in all groups. In patients with T2D, the frequency of KT complications increased from 21.08% in 2016 to 34.17% in 2020 (p<0.001). Patients with T2D had significantly more comorbidity than patients with T1D and patients without diabetes (p<0.001). Patients with T1D experienced KT rejection significantly more frequently (8.09%) than patients with T2D (5.57%).COVID-19 was recorded in 26 out of the 2444 KTs performed in 2020, being found in 6 of the 39 patients deceased that year (15.38%) and in 0.83% of the survivors.The variables associated with IHM were comorbidity and complications of KT. The presence of T1D was associated with IHM (OR 2.6; 95% CI 1.36 to 5.16) when patients without diabetes were the reference category. However, T2D was not associated with a higher IHM (OR 0.86; 95% CI 0.61 to 1.2). CONCLUSIONS: The COVID-19 pandemic led to a decrease in the number of transplants. Patients with T1D have more rejection of the transplanted organ than patients with T2D. Fewer women with T2D undergo KT. The presence of T1D is a risk factor for IHM.

Depth of Invasion: Influence of the Latest TNM Classification on the Prognosis of Clinical Early Stages of Oral Tongue Squamous Cell Carcinoma and Its Association with Other Histological Risk Factors.

BACKGROUND: The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors. METHODS: A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan-Meier method. Statistical significance was established for p values below 0.05. RESULTS: Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival (p = 0.043), but not with respect to overall survival (p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes (p = 0.012), perineural invasion (p = 0.004) and tumour differentiation grade (p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion. CONCLUSIONS: Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade.

Association between Hospital-Acquired Pneumonia and In-Hospital Mortality in Solid Organ Transplant Admissions: An Observational Analysis in Spain, 2004-2021.

(1) Background: To analyze the association between hospital-acquired pneumonia (HAP) and in-hospital mortality (IHM) during hospital admission for solid organ transplant in Spain during 2004-2021. (2) Methods: We used national hospital discharge data to select all hospital admissions for kidney, liver, heart, and lung transplants. We stratified the data according to HAP status. To examine time trends, we grouped data into three consecutive 6-year periods (2004-2009; 2010-2015; and 2016-2021). We assessed in-hospital mortality (IHM) in logistic regression analyses and obtained odds ratios (ORs) with their 95% confidence intervals (CIs). (3) Results: We identified a total of 71,827 transplants (45,262, kidney; 18,127, liver; 4734, heart; and 4598, lung). Two thirds of the patients were men. Overall, the rate of HAP during admission was 2.6% and decreased from 3.0% during 2004-2009 to 2.4% during 2016-2021. The highest rate of HAP corresponded to lung transplant (9.4%), whereas we found the lowest rate for kidney transplant (1.1%). Rates of HAP for liver and heart transplants were 3.8% and 6.3%, respectively. IHM was significantly lower during 2016-2021 compared to 2004-2009 for all types of transplants (ORs (CIs) = 0.65 (0.53-0.79) for kidney; 0.73 (0.63-0.84) for liver; 0.72 (0.59-0.87) for heart; and 0.39 (0.31-0.47) for lung). HAP was associated with IHM for all types of transplants (ORs (CIs) = 4.47 (2.85-9.08) for kidney; 2.96 (2.34-3.75) for liver; 1.86 (1.34-2.57) for heart; and 2.97 (2.24-3.94) for lung). (4) Conclusions: Rates of HAP during admission for solid organ transplant differ depending on the type of transplant. Although IHM during admission for solid organ transplant has decreased over time in our country, HAP persists and is associated with a higher IHM after accounting for potential confounding variables.

Mitochondrial mitophagy protection combining rivaroxaban and aspirin in high glucose-exposed human coronary artery endothelial cell. An in vitro study.

PURPOSE: Combination of Rivaroxaban plus Aspirin improved cardiovascular outcome in patients with stable cardiovascular disease. The aim was to determine if Rivaroxaban and acetylsalicylic acid alone or in combination may protect mitochondrial mitophagy in human coronary artery endothelial cells (HCAEC) exposed to D-glucose. METHODS: HCAEC were incubated under different conditions: 5 mmol/L glucose D-glucose (control), 30 mmol/L D-Glucose with and without 50 nmol/L Rivaroxaban (Rivaroxaban), 0.33 mmol/L ASA (ASA) or Rivaroxaban (12.5 nmol/L)+ASA (0.33 mmol/L; (Riva+ASA). RESULTS: HCAEC incubated with D-glucose showed an increased Factor Xa expression. The mitochondrial content of Pink-1 and Parkin were significantly reduced in high glucose-incubated HCAEC compared to control. Rivaroxaban+ASA significantly increased the mitochondrial content of Pink-1 and Parkin, and the mitochondrial membrane potential compared to D-Glucose group. Both ASA alone and Riva+ASA reduced reactive oxygen species (ROS) and tissue factor production induced by high glucose exposure. CONCLUSION: Under high glucose condition combining Rivaroxaban+ASA increased the mitochondrial content of Pink-1 and Parkin, restored mitochondria membrane potential and reduced ROS and tissue factor expression in HCAEC. It suggests potential effects induced by dual use of Rivaroxaban and ASA on the coronary endothelium subjected to high glucose condition.

Mental health in patients with asthma: A population-based case-control study.

BACKGROUND: This study's objectives were to compare the prevalence of mental disorders and consumption of psychiatric medications in asthmatic subjects with non-asthmatic controls and identify risk factors associated with psychiatric conditions. METHODS: This was an epidemiological case-control study based on the 2020 European Health Survey in Spain self-reported data. Each asthmatic subject was paired with a non-asthmatic control. Study variables included demographics, use of healthcare services, comorbidities, and risky behaviours were compared. RESULTS: There were 22,072 participants in the survey; 1151 cases and 1151 controls were selected. The prevalence of mental disorders (25.5% versus 13.4%; p < 0.001) and consumption of psychiatric medications (25.8% versus 15.6%; p < 0.001) were higher in cases than controls. In asthmatic subjects, female gender (OR 1.814; p = 0.001), age over 80 years (OR 2.558; p = 0.002), poor self-rated health (OR 2.047; p < 0.001), visits to a psychologist (OR 10.854; p < 0.001) and chronic pain (OR 1.938; p < 0.001) were independently associated with mental disorder diagnoses. Meanwhile, female sex (OR 1.710; p < 0.001), age over 80 years (OR 3.802; p < 0.001), poor self-rated health (OR 2.482; p < 0.001), visits to a psychologist (OR 2.694; p < 0.001) and chronic pain (OR 1.494; p = 0.012) were risk factors independently associated with psychiatric medication consumption. CONCLUSIONS: The prevalence of psychiatric conditions were higher in asthmatic subjects. Female gender, older age, worse self-rated health, visits to a psychologist and chronic pain were associated with psychiatric conditions in asthmatic subjects.

Time Trends in Spain from 2001 to 2018 in the Incidence and Outcomes of Hospitalization for Urinary Tract Infections in Patients with Type 2 Diabetes Mellitus.

We aim to examine the incidences, clinical characteristics, and in-hospital outcomes of type 2 diabetes (T2DM) patients hospitalized with urinary tract infections (UTIs) in Spain and to identify the factors associated with in-hospital mortality (IHM). A retrospective observational study was carried out with a sample that included all adult patients who were hospitalized for UTIs between 2001 and 2018 and collected in the Spanish National Health System Hospital Discharge Database. We identified 850,276 patients with UTIs (25.49% with T2DM). The incidence of UTIs increased in patients with and without diabetes from 290.76 and 74.79 cases per 100,000 inhabitants in the period from year 2001 to year 2003 to 568.45 and 144.0 in the period from 2016 to 2018, respectively (p < 0.001). Adjusted incidence of UTIs was higher in T2DM patients (incidence rate ratio (IRR) 4.36; 95% CI 4.35-4.39). The multivariable analysis showed a significant reduction in the IHM over time for men and women with T2DM. In T2DM, patients' higher IHM was associated with older age, comorbidities, and Staphylococcus aureus isolation. Women with T2DM had a higher risk of dying than men. The risk of IHM with an episode of UTIs was independent of the presence of T2DM (odds ratio (OR) 0.97; 95% CI 0.91-1.01). We conclude that the incidence of UTIs was over four times higher in T2DM than nondiabetic patients and has increased over time.

The Impact of COPD in Trends of Urinary Tract Infection Hospitalizations in Spain, 2001-2018: A Population-Based Study Using Administrative Data.

(1) Background: To examine trends in incidence and outcomes of urinary tract infections (UTIs) among men and women with or without chronic obstructive pulmonary disease (COPD), and to identify the predictors for in-hospital mortality (IHM). (2) Methods: We included patients (aged ≥40 years) who were hospitalized with UTIs between 2001 and 2018. Data were collected from the Spanish National Hospital Discharge Database. (3) Results: We identified 748,458 UTI hospitalizations, 6.53% with COPD. The UTIs incidence increased over time. It was 1.55 times higher among men COPD patients than among non-COPD men (incidence rate ratio (IRR) 1.55; 95% CI 1.53-1.56). The opposite happened in women with COPD compared to non-COPD women (IRR 0.30; 95% CI 0.28-0.32). IHM was higher in men with COPD than non-COPD men (5.58% vs. 4.47%; p < 0.001) and the same happened in women (5.62% vs. 4.92%; p < 0.001). The risk of dying increased with age and comorbidity, but the urinary catheter was a protective factor among men (OR 0.75; 95% CI 0.64-0.89). Multivariable analysis showed a significant reduction in the IHM over time for men and women with COPD. Suffering from COPD only increased the risk of IHM among men (OR 1.07; 95% CI 1.01-1.13). (4) Conclusions: The incidence of UTIs increased over time. Suffering COPD increased the risk of IHM among men, but not among women.

Type 2 Diabetes Is a Risk Factor for Suffering and for in-Hospital Mortality with Pulmonary Embolism. A Population-Based Study in Spain (2016-2018).

(1) Background: The relationship between type 2 diabetes (T2DM) and pulmonary embolism (PE) has not been well stablished so far. We aim to analyze incidence, clinical conditions and in-hospital mortality (IHM) according to the presence of T2DM among patients hospitalized for suffering from PE. The factors associated with IHM were identified. (2) Methods: Patients aged ≥40 years hospitalized for PE from 2016 to 2018 included in the Spanish National Health System Hospital Discharge Database were analyzed. Dependent variables included incidence, IHM and length of hospital stay. Independent variables were age, sex, diagnosed comorbidities, thrombolytic therapy and inferior vena cava filter placement. Poisson and logistic regression models were constructed for multivariable analysis. (3) Results: Of the 47,190 hospitalizations for PE recorded, 16.52% had T2DM. Adjusted incidence of PE was higher among T2DM women (IRR 1.83; 95% CI: 1.58-1.96) and men (IRR 1.22; 95% CI: 1.18-1.27) than among non-diabetic subjects. Crude IHM in T2DM patients with PE was similar in both sexes but higher than in non-diabetic patients. Among T2DM patients with PE, risk factors for IHM included older age, comorbidity, atrial fibrillation and massive PE. Obesity was associated with lower IHM. Suffering T2DM was a risk of IHM (OR 1.15; 95% CI 1.05-1.26) after PE. (4) Conclusions: The incidence of PE is higher in T2DM men and women than in non-diabetic patients. T2DM was a risk factor for IHM after PE.

Changing Trends in Hospital Admissions for Pulmonary Embolism in Spain from 2001 to 2018.

(1) Background: The aims of this study were to examine trends in the incidence, clinical characteristics, and in-hospital outcomes of patients hospitalized with pulmonary embolism in Spain and to identify factors associated with in-hospital mortality (IHM). (2) Methods: We included all patients who were hospitalized for pulmonary embolism between 2001 and 2018. Data were collected from the Spanish National Hospital Discharge Database. (3) Results: We identified 241,821 hospitalizations for pulmonary embolism during the study period. The incidence of pulmonary embolism increased from 20.49 cases per 100,000 inhabitants in the period 2001-2002 to 35.9 cases in the period 2017-2018 (p < 0.001). After controlling for possible confounders, there was a significant increase in the incidence over the study period (adjusted incidence rate ratio 1.53, 95% Confidence Interval I 1.51-1.56). The median length of hospital stay was 11 days in the period 2001-2002, decreasing to seven days in the period 2017-2018 (p < 0.001). For the total time period, the crude IHM rate was 9.51%. After multivariable adjustment, IHM decreased significantly over time. The IHM was significantly higher in women, in patients suffering from more comorbidities, and in those with a massive pulmonary embolism. (4) Conclusions: Our results revealed an increase in the incidence of pulmonary embolism hospitalizations from 2001 to 2018 in Spain, with older patients being the most affected.

Trends and Predictors for the Uptake of Colon Cancer Screening Using the Fecal Occult Blood Test in Spain from 2011 to 2017.

Background: In Spain, colorectal cancer screening using the fecal occult blood test, targeted towards the 50-69 age bracket, was implemented on different dates. We aim to assess the temporal trend of colorectal cancer (CRC) screening uptake according to the year of screening implementation in each region and to identify predictors for the uptake of CRC screening. Methods: A cross-sectional study with 12,657 participants from the Spanish National Health Surveys 2011 and 2017 was used. Uptake rates were analyzed according to the date that the screening program was implemented. Results: For regions with programs implemented before 2011, the uptake rate increased 3.34-fold from 2011 to 2017 (9.8% vs. 32.7%; p < 0.001). For regions that implemented screening within the 2011-2016 period, the uptake rose from 4.3% to 13.2% (3.07-fold; p < 0.001), and for regions that implemented screening after 2016, the uptake increased from 3.4% to 8.8% (2.59-fold; p < 0.001). For the entire Spanish population, the uptake increased 3.21-fold (6.8% vs. 21.8%; p < 0.001). Positive predictors for uptake were older age, Spanish nationality, middle-to-high educational level, suffering chronic diseases, non-smoking and living in regions where screening programs were implemented earlier. Conclusions: The different periods for the implementation of CRC screening as well as sociodemographic and health inequalities may have limited the improvement in the screening uptake from 2011 to 2017 in Spain.

Cytoplasmic Increase in Hsp70 Protein: A Potential New Biomarker of Early Infiltration of Cutaneous Squamous Cell Carcinoma Arising from Actinic Keratosis.

BACKGROUND: Cutaneous squamous skin cell carcinoma (SCC) is the second most frequent type of non-melanoma skin cancer and is the second leading cause of death by skin cancer in Caucasian populations. However, at present it is difficult to predict patients with poor SCC prognosis. OBJECTIVE: To identify proteins with expression levels that could predict SCC infiltration in SCC arising from actinic keratosis (SCC-AK). METHODS: A total of 20 biopsies from 20 different patients were studied; 10 were SCC-AK samples and 10 were taken from normal skin. Early infiltrated SCC-AK samples were selected based on histological examination, and to determine the expression of proteins, fresh skin samples were processed by two-dimensional electrophoresis. RESULTS: The expression levels of three proteins, namely alpha hemoglobin and heat shock proteins 27 and 70 (Hsp27 and Hsp70, respectively) were significantly increased in SCC-AK samples with respect to normal control skin. However, only the expression level of Hsp70 protein positively correlated with the level of SCC-AK dermis infiltration. Immunohistological examination suggested that increased expression of Hsp70 proteins seemed to mainly occur in the cytoplasm of keratinocytes. The increased cytoplasmic Hsp70 expression in SCC-AK was confirmed by Western blot experiments. CONCLUSION: Cytoplasmic expression of Hsp70 could be a potential biomarker of early infiltration of SCC arising from AK.

Effect of Pectin on the Expression of Proteins Associated with Mitochondrial Biogenesis and Cell Senescence in HT29-Human Colorectal Adenocarcinoma Cells.

Mitochondria dynamic is regulated by different proteins, maintaining a balance between fission and fusion. An imbalance towards mitochondrial fission has been associated with tumor cell proliferation. The aim of this study was to analyze whether pectin modifies the viability of human colon cancer cells and the expression of proteins involved in mitochondrial fusion and fission. The human colon carcinoma cell line HT29 cells was growth in 10% fetal bovine serum in the absence and presence of pectin. Pectin reduced HT29 cell viability in a concentration-dependent manner, reaching a plateau at 150~300 µmol/L pectin. The presence of 200 µmol/L pectin reduced the expression of dynamin-related protein-1 and increased expression of the mitochondrial fusion-associated proteins mitofusin-1 and 2. Expression of cyclin B1, a protein involved in G2/M transition, was found decreased in pectin-incubated HT29 cells. Moreover, expression of p53 protein, the amount of p53 in the nucleous and ß-galactosidase activity, which are all biomarkers for cellular senescence, were significantly higher in pectin-incubated HT29 cells than in HT29 cells incubated without pectin. Expression of the protein B-cell lymphoma 2 (Bcl-2) homologous antagonist/killer was increased in response to incubation with pectin. However, incubation with pectin did not affect expression of Bcl-2-associated X protein or Bcl-2, or the caspase-3 activity. Overall, we concluded that pectin reduces the viability of human HT29 colon cancer cells, which is accompanied with a shift in the expression of proteins associated with mitochondrial dynamics towards mitochondrial fusion. Moreover, incubation with pectin favors cellular senescence over apoptosis in HT29 cells.

Effects of coronary prestenting platelet inhibition on coronary poststenting inflammation.

The aim of this study was to analyze the effect of 2 antiplatelet regimens on the inhibition of GP IIb/IIIa-dependent platelet activation and their association with the poststenting inflammatory response. Seventeen patients with acute myocardial infarction were divided into 2 groups: (A) clopidogrel plus tirofiban infusion administered together during inclusion (n = 10); (B) clopidogrel administered at inclusion and followed 2 hours after by tirofiban (n = 7). Blood samples were obtained at inclusion and at 24 and 48 hours after stenting. Before stenting, a greater reduction of GP IIb/IIIa-dependent platelet activation was found in both groups, although it was greater in group A than in group B. This statistical difference was not observed at 24 and 48 hours after the procedure. At 48 hours after stenting, interleukin-6, interleukin-10, soluble intracellular adhesion molecule-1, and soluble CD40 ligand plasma values were not different between experimental groups. By proteomics, different isoforms of the following proteins were identified: alpha 1-antitrypsin (ATT-1), fibrinogen gamma chain, apolipoprotein A-IV, apolipoprotein A-I, vitamin D binding protein, haptoglobin, and serotransferrin. At 48 hours after stenting, only the plasma expression of the ATT-1 isoform 5 was significantly increased in group A compared with group B. In conclusion, a greater inhibition of GP IIb/IIIa-dependent platelet activation before stenting was not correlated with a different inflammatory activity early after stenting.