Breast segmentation in infrared thermography from characteristical inframammary shape.

Infrared thermography is gaining relevance in breast cancer assessment. For this purpose, breast segmentation in thermograms is an important task for performing automatic image analysis and detecting possible temperature changes that indicate the presence of malignancy. However, it is not a simple task since the breast limit borders, especially the top borders, often have low contrast, making it difficult to isolate the breast area. Several algorithms have been proposed for breast segmentation, but these highly depend on the contrast at the lower breast borders and on filtering algorithms to remove false edges. This work focuses on taking advantage of the distinctive inframammary shape to simplify the definition of the lower breast border, regardless of the contrast level, which indeed also provides a strong anatomical reference to support the definition of the poorly marked upper boundary of the breasts, which has been one of the major challenges in the literature. In order to demonstrate viability of the proposed technique for an automatic breast segmentation, we applied it to a database with 180 thermograms and compared their results with those reported by others in the literature. We found that our approach achieved a high performance, in terms of Intersection over Union of 0.934, even higher than that reported by artificial intelligence algorithms. The performance is invariant to breast sizes and thermal contrast of the images.

Faecal proteomics links neutrophil degranulation with mortality in patients with alcohol-associated hepatitis.

OBJECTIVE: Patients with alcohol-associated hepatitis (AH) have a high mortality. Alcohol exacerbates liver damage by inducing gut dysbiosis, bacterial translocation and inflammation, which is characterised by increased numbers of circulating and hepatic neutrophils. DESIGN: In this study, we performed tandem mass tag (TMT) proteomics to analyse proteins in the faeces of controls (n=19), patients with alcohol-use disorder (AUD; n=20) and AH (n=80) from a multicentre cohort (InTeam). To identify protein groups that are disproportionately represented, we conducted over-representation analysis using Reactome pathway analysis and Gene Ontology to determine the proteins with the most significant impact. A faecal biomarker and its prognostic effect were validated by ELISA in faecal samples from patients with AH (n=70), who were recruited in a second and independent multicentre cohort (AlcHepNet). RESULT: Faecal proteomic profiles were overall significantly different between controls, patients with AUD and AH (principal component analysis p=0.001, dissimilarity index calculated by the method of Bray-Curtis). Proteins that showed notable differences across all three groups and displayed a progressive increase in accordance with the severity of alcohol-associated liver disease were predominantly those located in neutrophil granules. Over-representation and Reactome analyses confirmed that differentially regulated proteins are part of granules in neutrophils and the neutrophil degranulation pathway. Myeloperoxidase (MPO), the marker protein of neutrophil granules, correlates with disease severity and predicts 60-day mortality. Using an independent validation cohort, we confirmed that faecal MPO levels can predict short-term survival at 60 days. CONCLUSIONS: We found an increased abundance of faecal proteins linked to neutrophil degranulation in patients with AH, which is predictive of short-term survival and could serve as a prognostic non-invasive marker.

Pregnant Women with Multiple Sclerosis: An Overview of Gene Expression and Molecular Interaction Using Bioinformatics Analysis.

Multiple sclerosis (MS) is a common disease in young women of reproductive age, characterized by demyelination of the central nervous system (CNS). Understanding how genes related to MS are expressed during pregnancy can provide insights into the potential mechanisms by which pregnancy affects the course of this disease. This review article presents evidence-based studies on these patients' gene expression patterns. In addition, it constructs interaction networks using bioinformatics tools, such as STRING and KEGG pathways, to understand the molecular role of each of these genes. Bioinformatics research identified 25 genes and 21 signaling pathways, which allows us to understand pregnancy patients' genetic and biological phenomena and formulate new questions about MS during pregnancy.

Serum aryl hydrocarbon receptor activity is associated with survival in patients with alcohol-associated hepatitis.

BACKGROUND AND AIMS: Patients with alcohol-associated hepatitis (AH) have an altered fecal metabolome, including reduced microbiota-derived tryptophan metabolites, which function as ligands for aryl hydrocarbon receptor (AhR). The aim of this study was to assess serum AhR ligand activity in patients with AH. APPROACH AND RESULTS: The study included 74 controls without AUD, 97 patients with AUD, and 330 patients with AH from 2 different multicenter cohorts (InTeam: 134, AlcHepNet: 196). Serum AhR activity was evaluated using an AhR reporter assay with HepG2-Lucia cells incubated with serum for 24 hours. Serum AhR activity was significantly higher in patients with AH compared with both controls (1.59 vs. 0.96-fold change, p < 0.001) and patients with AUD (1.59 vs. 0.93, p < 0.001). In both AH cohorts, patients with AhR activity ≥ 2.09 had significantly lower cumulative survival rates at 30, 60, 90, and 180 days compared to those with AhR activity < 2.09. When serum AhR activity was used to further stratify patients with severe AH, the cumulative 30, 60, 90, and 180-day survival rates for patients with severe AH and the AhR activity ≥ 2.09 group were all significantly lower than those with an AhR activity < 2.09 group. CONCLUSIONS: Serum AhR activity was significantly higher in patients with AH compared with controls and individuals with AUD, and this increased activity was associated with higher mortality. Consequently, serum AhR activity holds potential as a prognostic marker.

Safety, Efficacy and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Treatment of Mild-to-Moderate COVID-19: 15-Month Final Analysis of the TACKLE Trial.

INTRODUCTION: In the phase 3 TACKLE study, outpatient treatment with AZD7442 (tixagevimab/cilgavimab) was well tolerated and significantly reduced progression to severe disease or death through day 29 in adults with mild-to-moderate coronavirus disease 2019 (COVID-19) at the primary analysis. Here, we report data from the final analysis of the TACKLE study, performed after approximately 15 months' follow-up. METHODS: Eligible participants were randomized 1:1 and dosed within 7 days of symptom onset with 600 mg intramuscular AZD7442 (n = 456; 300 mg tixagevimab/300 mg cilgavimab) or placebo (n = 454). RESULTS: Severe COVID-19 or death through day 29 occurred in 4.4% and 8.8% of participants who received AZD7442 or placebo, a relative risk reduction (RRR) of 50.4% [95% confidence interval (CI) 14.4, 71.3; p = 0.0096]; among participants dosed within 5 days of symptom onset, the RRR was 66.9% (95% CI 31.1, 84.1; p = 0.002). Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 occurred in 5.0% of participants receiving AZD7442 versus 9.7% receiving placebo, an RRR of 49.2% (95% CI 14.7, 69.8; p = 0.009). Adverse events occurred in 55.5% and 55.9% of participants who received AZD7442 or placebo, respectively, and were mostly mild or moderate in severity. Serious adverse events occurred in 10.2% and 14.4% of participants who received AZD7442 or placebo, respectively, and deaths occurred in 1.8% of participants in both groups. Serum concentration-time profiles recorded over 457 days were similar for AZD7442, tixagevimab, and cilgavimab, and were consistent with the extended half-life reported for AZD7442 (approx. 90 days). CONCLUSIONS: AZD7442 reduced the risk of progression to severe COVID-19, hospitalization, and death, was well tolerated through 15 months, and exhibited predictable pharmacokinetics in outpatients with mild-to-moderate COVID-19. These data support the long-term safety of using long-acting monoclonal antibodies to treat COVID-19. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04723394. ( https://clinicaltrials.gov/study/NCT04723394 .

The body's immune system produces proteins called antibodies that specifically target foreign substances such as viruses. AZD7442 is a combination of two antibodies (called tixagevimab and cilgavimab) that bind to the severe acute respiratory syndrome coronavirus 2 virus spike protein, preventing it from causing coronavirus disease 2019 (COVID-19). AZD7442 was designed to be "long-acting" and therefore provide prolonged protection against COVID-19 lasting several months from a single dose. It was tested in a clinical trial (TACKLE) to see if it could prevent people who had recently developed symptoms of COVID-19 from getting sicker, being hospitalized, or dying. Around 900 adults took part in this clinical trial. Half of this group were treated with a dose of AZD7442, given as two injections. The other half received a placebo (injections that look like the AZD7442 injections but contain no medicine). The effect of AZD7442 treatment against COVID-19 was monitored over 6 months, and safety was monitored over 15 months. Around the same percentage of participants in the trial reported side effects with AZD7442 and placebo, suggesting there were no safety issues with AZD7442. AZD7442 treatment reduced the risk of participants getting severe COVID-19 or dying from COVID-19 by approximately half, compared with the placebo group. Participants receiving AZD7442 also had fewer hospitalizations due to COVID-19 complications, compared with the placebo group. These results showed the long-term safety of using long-acting antibodies such as AZD7442 as a treatment for COVID-19.

Analysis of SARS-CoV-2 Emergent Variants Following AZD7442 (Tixagevimab/Cilgavimab) for Early Outpatient Treatment of COVID-19 (TACKLE Trial).

INTRODUCTION: AZD7442 (tixagevimab/cilgavimab) comprises neutralising monoclonal antibodies (mAbs) that bind to distinct non-overlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Viral evolution during mAb therapy can select for variants with reduced neutralisation susceptibility. We examined treatment-emergent SARS-CoV-2 variants during TACKLE (NCT04723394), a phase 3 study of AZD7442 for early outpatient treatment of coronavirus disease 2019 (COVID-19). METHODS: Non-hospitalised adults with mild-to-moderate COVID-19 were randomised and dosed ≤ 7 days from symptom onset with AZD7442 (n = 452) or placebo (n = 451). Next-generation sequencing of the spike gene was performed on SARS-CoV-2 reverse-transcription polymerase chain reaction-positive nasopharyngeal swabs at baseline and study days 3, 6, and 15 post dosing. SARS-CoV-2 lineages were assigned using spike nucleotide sequences. Amino acid substitutions were analysed at allele fractions (AF; % of sequence reads represented by substitution) ≥ 25% and 3% to 25%. In vitro susceptibility to tixagevimab, cilgavimab, and AZD7442 was evaluated for all identified treatment-emergent variants using a pseudotyped microneutralisation assay. RESULTS: Longitudinal spike sequences were available for 461 participants (AZD7442, n = 235; placebo, n = 226) and showed that treatment-emergent variants at any time were rare, with 5 (2.1%) AZD7442 participants presenting ≥ 1 substitution in tixagevimab/cilgavimab binding sites at AF ≥ 25%. At AF 3% to 25%, treatment-emergent variants were observed in 15 (6.4%) AZD7442 and 12 (5.3%) placebo participants. All treatment-emergent variants showed in vitro susceptibility to AZD7442. CONCLUSION: These data indicate that AZD7442 creates a high genetic barrier for resistance and is a feasible option for COVID-19 treatment.

Real-World Insights into Evolocumab Use in Patients with Hyperlipidemia Across Five Countries: Analysis from the ZERBINI Study.

INTRODUCTION: This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries. METHODS: This retrospective and prospective observational study enrolled patients initiated on evolocumab during August 2017 to July 2019 at 49 sites across Canada, Mexico, Colombia, Saudi Arabia and Kuwait. Medical records data were extracted within 6 months prior to (baseline) and every 3 months for 12 months post evolocumab initiation and reported as available. RESULTS: A total of 578 patients were enrolled (40.1% female, median age 60 [interquartile range (IQR) 51-68] years); 83.7% had atherosclerotic cardiovascular disease and/or familial hypercholesterolemia. Median low-density lipoprotein cholesterol (LDL-C) at baseline was 3.4 (IQR 2.7-4.2) mmol/L (131.5 [IQR 104.4-162.4] mg/dL), with 75.6% of patients receiving a statin (59.2% high intensity). Compared to baseline, the median lowest LDL-C was reduced by 70.2% and remained stable over 12 months of treatment. Guideline-recommended LDL-C thresholds < 1.8, < 1.4 and < 1.0 mmol/L (< 70, < 55 and < 40 mg/dL) were achieved by 75.3%, 63.6% and 47.4% of patients. LDL-C outcomes were consistent across high- and very high-risk patients. Background lipid-lowering therapy remained relatively stable. No serious treatment-emergent adverse events were reported, and persistence to evolocumab was 90.2% at 12 months. CONCLUSION: These findings provide real-world evidence that evolocumab use is in accordance with its international guideline-recommended place in dyslipidemia therapy, as well as confirmation of its effectiveness and safety in a heterogeneous population. Evolocumab can address a healthcare gap in the management of dyslipidemia by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk.

Outpatient Treatment with AZD7442 (Tixagevimab/Cilgavimab) Prevented COVID-19 Hospitalizations over 6 Months and Reduced Symptom Progression in the TACKLE Randomized Trial.

INTRODUCTION: We assessed effects of AZD7442 (tixagevimab/cilgavimab) on deaths from any cause or hospitalizations due to coronavirus disease 2019 (COVID-19) and symptom severity and longer-term safety in the TACKLE adult outpatient treatment study. METHODS: Participants received 600 mg AZD7442 (n = 452) or placebo (n = 451) ≤ 7 days of COVID-19 symptom onset. RESULTS: Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 (key secondary endpoint) occurred in 20/399 (5.0%) participants receiving AZD7442 versus 40/407 (9.8%) receiving placebo [relative risk reduction (RRR) 49.1%; 95% confidence interval (CI) 14.5, 69.7; p = 0.009] or 50.7% (95% CI 17.5, 70.5; p = 0.006) after excluding participants unblinded before day 169 for consideration of vaccination). AZD7442 reduced progression of COVID-19 symptoms versus placebo through to day 29 (RRR 12.5%; 95% CI 0.5, 23.0) and improved most symptoms within 1-2 weeks. Over median safety follow-up of 170 days, adverse events occurred in 174 (38.5%) and 196 (43.5%) participants receiving AZD7442 or placebo, respectively. Cardiac serious adverse events occurred in two (0.4%) and three (0.7%) participants receiving AZD7442 or placebo, respectively. CONCLUSIONS: AZD7442 was well tolerated and reduced hospitalization and mortality through 6 months, and symptom burden through 29 days, in outpatients with mild-to-moderate COVID-19. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04723394. ( https://beta. CLINICALTRIALS: gov/study/NCT04723394 ).

Antibodies are proteins produced by the body's immune system to specifically combat foreign substances, such as viruses. Tixagevimab and cilgavimab are a pair of antibodies that bind to a specific part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). When they bind to the virus, they reduce its ability to cause disease. These antibodies were tested in a clinical trial to see if they could prevent people with COVID-19 from being hospitalized or dying. Around 900 adults took part in this clinical trial. These people all had COVID-19 but were not sick enough to be in hospital. Half of this group were treated with a dose of tixagevimab and cilgavimab, given as two injections. The other half received a placebo (injections that look exactly like the tixagevimab and cilgavimab injections but contain no medicine). The study found that, over 6 months, people with COVID-19 who received tixagevimab and cilgavimab were less likely to need to go to hospital than people who received the placebo. They were also less likely to die of COVID-19. Tixagevimab and cilgavimab also helped to improve COVID-19 symptoms. People who received the antibodies saw their symptoms improve faster than people who received the placebo. They were also less likely to have symptoms that got worse. Most people felt better within 1­2 weeks of getting treatment. No safety issues were found with tixagevimab and cilgavimab compared with placebo.

Suicidal ideation among people with Parkinson's disease and comparison with a control group.

BACKGROUND: Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease (PwPD) and to compare them with a control group. METHODS: PD patients and controls recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. Two visits were conducted: V0 (baseline); V2 (2-year ± 1 month follow-up). SI was defined as a score ≥1 on item nine of the Beck Depression Inventory-II (BDI-II). Regression analyses were conducted to identify factors related to SI. RESULTS: At baseline, 693 PwPD (60.2% males; 62.59 ± 8.91 years old) and 207 controls (49.8% males; 60.99 ± 8.32 years old) were included. No differences between PwPD and controls were detected in SI frequency at either V0 (5.1% [35/693] vs. 4.3% [9/207]; p = 0.421) or at V2 (5.1% [26/508] vs. 4.8% [6/125]; p = 0.549). Major depression (MD) and a worse quality of life were associated with SI at both visits in PwPD: V0 (MD, OR = 5.63; p = 0.003; PDQ-39, OR = 1.06; p = 0.021); V2 (MD, OR = 4.75; p = 0.027; EUROHIS-QOL8, OR = 0.22; p = 0.006). A greater increase in the BDI-II total score from V0 to V2 was the only factor predicting SI at V2 (OR = 1.21; p = 0.002) along with an increase in the total number of non-antiparkinsonian drugs (OR = 1.39; p = 0.041). CONCLUSION: The frequency of SI (5%) in PwPD was similar to in controls. Depression, a worse quality of life, and a greater comorbidity were related to SI.

Prevalence and Factors Associated with Drooling in Parkinson's Disease: Results from a Longitudinal Prospective Cohort and Comparison with a Control Group.

Introduction: Drooling in Parkinson's disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results: The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032; p = 0.012), being male (OR = 2.333; p < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020; p < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR = 1.012; p < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with ≤2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR = 1.121; p = 0.007) as a predictor of drooling at V2. Conclusion: Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden.

Staging Parkinson's Disease According to the MNCD (Motor/Non-motor/Cognition/Dependency) Classification Correlates with Disease Severity and Quality of Life.

BACKGROUND: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). OBJECTIVE: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. METHODS: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). RESULTS: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. CONCLUSION: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.

Sex Differences in Motor and Non-Motor Symptoms among Spanish Patients with Parkinson's Disease.

BACKGROUND AND OBJECTIVE: Sex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD. PATIENTS AND METHODS: PD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used. RESULTS: At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; p = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; p = 0.259). Symptoms such as depression (p < 0.0001), fatigue (p < 0.0001), and pain (p < 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (p < 0.0001), speech problems (p < 0.0001), rigidity (p < 0.0001), and hypersexuality (p < 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (p = 0.002). Perception of quality of life was generally worse in females (PDQ-39, p = 0.002; EUROHIS-QOL8, p = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (p = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (p = 0.001). CONCLUSION: The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.

Risk of Cognitive Impairment in Patients With Parkinson's Disease With Visual Hallucinations and Subjective Cognitive Complaints.

BACKGROUND AND PURPOSE: Visual hallucinations (VH) and subjective cognitive complaints (SCC) are associated with cognitive impairment (CI) in Parkinson's disease. Our aims were to determine the association between VH and SCC and the risk of CI development in a cohort of patients with Parkinson's disease and normal cognition (PD-NC). METHODS: Patients with PD-NC (total score of >80 on the Parkinson's Disease Cognitive Rating Scale [PD-CRS]) recruited from the Spanish COPPADIS cohort from January 2016 to November 2017 were followed up after 2 years. Subjects with a score of ≥1 on domain 5 and item 13 of the Non-Motor Symptoms Scale at baseline (V0) were considered as "with SCC" and "with VH," respectively. CI at the 2-year follow-up (plus or minus 1 month) (V2) was defined as a PD-CRS total score of <81. RESULTS: At V0 (n=376, 58.2% males, age 61.14±8.73 years [mean±SD]), the frequencies of VH and SCC were 13.6% and 62.2%, respectively. VH were more frequent in patients with SCC than in those without: 18.8% (44/234) vs 4.9% (7/142), p<0.0001. At V2, 15.2% (57/376) of the patients had developed CI. VH presenting at V0 was associated with a higher risk of CI at V2 (odds ratio [OR]=2.68, 95% confidence interval=1.05-6.83, p=0.0.039) after controlling for the effects of age, disease duration, education, medication, motor and nonmotor status, mood, and PD-CRS total score at V0. Although SCC were not associated with CI at V2, presenting both VH and SCC at V0 increased the probability of having CI at V2 (OR=3.71, 95% confidence interval=1.36-10.17, p=0.011). CONCLUSIONS: VH were associated with the development of SCC and CI at the 2-year follow-up in patients with PD-NC.

Falls Predict Acute Hospitalization in Parkinson's Disease.

BACKGROUND: There is a need for identifying risk factors for hospitalization in Parkinson's disease (PD) and also interventions to reduce acute hospital admission. OBJECTIVE: To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort. METHODS: PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed on time to hospital encounter 1-year after the baseline visit. RESULTS: Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up after the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065-5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319-6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757-8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124-4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080-8.322; p = 0.035) was an independent predictor of AH. CONCLUSION: Falls is an independent predictor of AH in PD patients.

Incidence of injuries among lacrosse athletes: a systematic review and meta-analysis.

OBJECTIVES: The purpose of this systematic review was to determine the incidence of injuries among lacrosse athletes and the differences in rates of injury by location and gender. METHODS: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were implemented to conduct this systematic review.[1] The following variables were extracted from each of the included articles: location of injury, gender of patient, and incidence of injury among study population. The methodological quality of the included studies was assessed using mixed-methods appraisal tool (MMAT) version 2018.[2] Estimated rates were reported as pooled proportion with 95% CI. Rates of injury were calculated as a rate per 1000 athletic exposures (AEs), defined as an athlete participating in 1 practice or competition in which he or she was exposed to the possibility of athletic injury. RESULTS: This study found that the highest injury rate among lacrosse athletes was to the lower leg/ankle/foot with a rate of 0.66 injuries per 1000 AEs (95% CI, 0.51, 0.82). This injury pattern was also found to be the highest among both male and female lacrosse athletes. No statistical significance was detected when comparing rates of injury across gender, regardless of location. The injury pattern with the lowest rates of injury for female athletes being to the shoulder/clavicle and the neck for male athletes. CONCLUSION: The highest rate of injury among lacrosse athletes was to the lower leg/ankle/foot. As participation in lacrosse continues to rise, there is a greater need for understanding the rate of injury and injury characteristics for physicians and trainers to provide effective care to lacrosse athletes.

Inflammatory bowel disease: The role of commensal microbiome in immune regulation / Enfermedad inflamatoria intestinal: el rol de microbioma comensal en la regulación inmune

The incidence of inflammatory bowel disease (IBD) is increasing. Microbiome is one of the most important factors in its development and affects the different clinical outcomes of IBD patients depending on its composition and different alterations. We conducted a systematic review to discuss the association between microbiome and IBD in terms of immune regulation, and therapies that can modify microbiota. A comprehensive systematic literature search was performed through April 2020 in PubMed, Web of Science, the Cochrane Library, and clinicaltrials.gov. Inclusion criteria required IBD immune regulation and alternate therapeutics for IBD. This analysis helps explain the multifactorial origin of microbiome diversity including normal immune regulation, immune pathophysiology of IBD, and shows the evidence of several therapeutic targets to change microbiome in patients with IBD, such as prebiotics, probiotics, antibiotics, fecal microbiota transplant, and others.(AU)

La incidencia en enfermedad inflamatoria intestinal (EII) va en aumento. El microbioma es uno de los factores más importantes en su desarrollo y afecta los diferentes escenarios clínicos en pacientes con EII dependiendo de su composición y diferentes alteraciones. Se realizó una revisión sistemática para discutir la asociación entre el microbioma y EII relacionado con inmunorregulación y las terapias que pueden modificar la microbiota. Se realizó una búsqueda en la literatura hasta abril de 2020 en Pubmed, Web of Science, Cochrane library y clinicaltrials.gov. La inclusión del material requiere EII, inmunorregulación y las terapias alternativas para EII. Este estudio ayuda a explicar el origen multifactorial de la diversidad del microbioma incluyendo la inmunorregulación normal, fisiopatología inmuno de EII y muestra la evidencia de diferentes blancos terapéuticos para cambiar el microbioma en pacientes con EII como prebióticos, probióticos, antibióticos, trasplante de materia fecal, entre otros.(AU)

Real-World Evidence Evaluation on the Lipid Profile, Therapeutic Goals, and Safety of the Fixed-Dose Combination of Rosuvastatin/Ezetimibe (Trezete®) in Dyslipidemia Patients.

Introduction: Cardiovascular diseases are the leading cause of death worldwide. The combination of statins and cholesterol-absorption inhibitors promotes the decrease in risk factors, such as high concentrations of LDL (low-density lipoproteins). The aim of the study was to evaluate changes in the lipid profile and the effect on therapeutic goals, as well as the safety of dyslipidemia patients treated with Rosuvastatin/Ezetimibe (Trezete®). Materials and Methods: A real-world evidence study was conducted with retrospective data collection through a review of clinical records from dyslipidemia patients treated with Trezete® in routine medical practice. Clinical records included results of biochemical markers before treatment and at least one follow up between weeks 8 and 16. Results: The study included 103 patients' clinical records (55.4% men) with a mean age of 56.0 ± 13.0 years. More than 57% of the patients had mixed dyslipidemia and a median disease progression of 3.1 (IQR, 1.5; 9.1) years. Regarding LDL concentrations, 72.8% of the patients achieved therapeutic goals according to cardiovascular risk (CVR), which was statistically significant. Similarly, 94.1% achieved goals for total cholesterol (<200 mg/dL) and 56.0% for triglycerides (<150 mg/dL), a p value <0.001. No cardiovascular events were observed. Conclusion: Trezete® shows an important clinical impact on CVR-related target markers during the treatment of dyslipidemia patients. It is relevant to mention that a significant percentage of patients achieved therapeutic goals during the first months of treatment. Fixed-dose combination therapy has shown to be as safe as monotherapy treatment. ClinicalTrials.gov Identifier: NCT04862962.

The Global Incidence of Peptic Ulcer Disease Is Decreasing Since the Turn of the 21st Century: A Study of the Organisation for Economic Co-Operation and Development (OECD).

INTRODUCTION: Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century. METHODS: The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models. RESULTS: The overall median hospitalization rate was 42.4 with an interquartile range of 29.7-60.6 per 100,000 person-years. On average, hospitalization rates (AAPC = -3.9%; 95% CI: -4.4, -3.3) and morality rates (AAPC = -4.7%; 95% CI: -5.6, -3.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021. DISCUSSION: PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum.

Clinical and structural brain correlates of hypomimia in early-stage Parkinson's disease.

BACKGROUND AND PURPOSE: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. METHODS: The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross-sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used. RESULTS: After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS-III speech and bradykinesia items and was significantly related to the severity of apathy (ß = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto-temporo-parietal regions involved in the decoding, recognition and production of facial expression of emotions. CONCLUSION: Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non-motor aspects converge.