Early Diagnosis of Sepsis: The Role of Biomarkers and Rapid Microbiological Tests.

Sepsis is a medical emergency resulting from a dysregulated response to an infection, causing preventable deaths and a high burden of morbidity. Protocolized and accurate interventions in sepsis are time-critical. Therefore, earlier recognition of cases allows for preventive interventions, early treatment, and improved outcomes. Clinical diagnosis of sepsis by clinical scores cannot be considered an early diagnosis, given that underlying molecular pathophysiological mechanisms have been activated in the preceding hour or days. There is a lack of a widely available tool enhancing preclinical diagnosis of sepsis. Sophisticated technologies for sepsis prediction have several limitations, including high costs. Novel technologies for fast molecular and microbiological diagnosis are focusing on bedside point-of-care combined testing to reach most settings where sepsis represents a challenge.

Reconstructing the environmental impact of mining on mountain lakes.

Mountain lakes are particularly fragile ecosystems undergoing important transformations associated with ongoing global change. However, the history of anthropogenic impacts on mountain lakes and their catchments is much longer, in many cases featuring millennia of summer pastoral farming. More recently, the growing demand for raw materials and energy linked to industrialization, particularly accelerated since the 19th century CE, meant a further increase in human impact on mountain areas. The Cantabrian Range (northern Spain) constitutes a paradigmatic case of southern European mountain range experiencing intense human impact during the past few millennia and particularly the past two centuries. Here, we have reconstructed the environmental dynamics of this area during the last millennium, with a particular focus on the impact of mining, based on the multidisciplinary analysis (sedimentology, biogeochemistry, magnetic susceptibility, diatoms, pollen, charcoal and dung fungal spores) of sediment cores from Lago de La Cueva (43°03'N, 6°06'W, 1550 m a.s.l.). Changing land use and climate have driven lake dynamics during the last centuries. A major fire-caused deforestation event dated to the late 15th century CE increased erosion and the frequency of intense runoff episodes, in the context of the wetter and colder Little Ice Age. The onset of iron mining activities in the catchment ca. 200 years ago had a strong impact on the lake. Sedimentation rates notably raised and mining waste containing hematite and potentially toxic elements (e.g. Fe, Co, As) was washed into the lake. Additionally, diatom assemblages showed that lake regulation since the early 20th century CE severely altered the natural hydrological regime introducing rapid seasonal lake-level oscillations and increased lakeshore erosion, water turbidity and nutrient loads. The recent environmental restoration, finished in 2006, has involved the re-deposition of large volumes of mine tailing. Although some mining wastewater still arrives into the lake because mine drainage is still active, restoration works have succeeded in reducing erosion rates and nutrient loads. Lower land-use intensity has also contributed to natural vegetation recovery, further diminishing erosion. This study illustrates the complex interactions between human activities (grazing, mining, hydropower) and climate change in defining mountain landscape shifts through time. Moreover, our results highlight the usefulness of paleolimnological research to quantitatively assess the effectiveness of lake restoration programs.

Characterization of a Ligilactobacillus salivarius Strain Isolated from a Cheese Seal Which Was Last Used in 1936.

Cheesemaking played a pivotal role in the life of the Pyrenean villages where cheese was a most prized commodity and the subject of much local competition. In one of them (Sasa de Sobrepuerto), Mrs. Sebastiana Palacio decided in 1877 to label all the cheeses made in her household with a seal to differentiate them from those made by other local producers. The cheese seal was last used in 1936 and, since then, it has been kept under excellent storage conditions. Since well-preserved cheese seals are rare, and bacterial cells may survive desiccation for long periods, the objective of this work was to isolate and characterize any lactic acid bacteria that survived in the seal. Analysis of the milky crust material revealed the presence of sheep caseins. Culture-based analysis led to the isolation of a strain of Bacillus licheniformis and a strain of Ligilactobacillus salivarius (L. salivarius SP36). The latter was characterized in vitro for safety and dairy-related functional properties. Its genome encodes several genes involved in protein, peptide, and amino acid catabolism, and flavor. Overall, the phenotypic and genetic features of this strain support a high potential for being used as adjunct culture in cheesemaking.

Femoral versus radial access for middle meningeal artery embolization for chronic subdural hematomas: multicenter propensity score matched study.

BACKGROUND: With transradial access (TRA) being more progressively used in neuroendovascular procedures, we compared TRA with transfemoral access (TFA) in middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH). METHODS: Consecutive patients undergoing MMAE for cSDH at 14 North American centers (2018-23) were included. TRA and TFA groups were compared using propensity score matching (PSM) controlling for: age, sex, concurrent surgery, previous surgery, hematoma thickness and side, midline shift, and pretreatment antithrombotics. The primary outcome was access site and overall complications, and procedure duration; secondary endpoints were surgical rescue, radiographic improvement, and technical success and length of stay. RESULTS: 872 patients (median age 73 years, 72.9% men) underwent 1070 MMAE procedures (54% TFA vs 46% TRA). Access site hematoma occurred in three TFA cases (0.5%; none required operative intervention) versus 0% in TRA (P=0.23), and radial-to-femoral conversion occurred in 1% of TRA cases. TRA was more used in right sided cSDH (58.4% vs 44.8%; P<0.001). Particle embolics were significantly higher in TFA while Onyx was higher in TRA (P<0.001). Following PSM, 150 matched pairs were generated. Particles were more utilized in the TFA group (53% vs 29.7%) and Onyx was more utilized in the TRA group (56.1% vs 31.5%) (P=0.001). Procedural duration was longer in the TRA group (median 68.5 min (IQR 43.1-95) vs 59 (42-84); P=0.038), and radiographic success was higher in the TFA group (87.3% vs 77.4%; P=0.036). No differences were noted in surgical rescue (8.4% vs 10.1%, P=0.35) or technical failures (2.4% vs 2%; P=0.67) between TFA and TRA. Sensitivity analysis in the standalone MMAE retained all associations but differences in procedural duration. CONCLUSIONS: In this study, TRA offered comparable outcomes to TFA in MMAE for cSDH in terms of access related and overall complications, technical feasibility, and functional outcomes. Procedural duration was slightly longer in the TRA group, and radiographic success was higher in the TFA group, with no differences in surgical rescue rates.

Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample.

Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth's death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.

Strategies to address diabetic kidney disease burden in Mexico: a narrative review by the Mexican College of Nephrologists.

Chronic kidney disease (CKD) is a growing global public health challenge worldwide. In Mexico, CKD prevalence is alarmingly high and remains a leading cause of morbidity and mortality. Diabetic kidney disease (DKD), a severe complication of diabetes, is a leading determinant of CKD. The escalating diabetes prevalence and the complex regional landscape in Mexico underscore the pressing need for tailored strategies to reduce the burden of CKD. This narrative review, endorsed by the Mexican College of Nephrologists, aims to provide a brief overview and specific strategies for healthcare providers regarding preventing, screening, and treating CKD in patients living with diabetes in all care settings. The key topics covered in this review include the main cardiometabolic contributors of DKD (overweight/obesity, hyperglycemia, arterial hypertension, and dyslipidemia), the identification of kidney-related damage markers, and the benefit of novel pharmacological approaches based on Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA). We also address the potential use of novel therapies based on Mineralocorticoid Receptor Antagonists (MRAs) and their future implications. Emphasizing the importance of multidisciplinary treatment, this narrative review aims to promote strategies that may be useful to alleviate the burden of DKD and its associated complications. It underscores the critical role of healthcare providers and advocates for collaborative efforts to enhance the quality of life for millions of patients affected by DKD.

[Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting]. / Mejorando la atención nutricional del paciente oncológico: validación de un protocolo multidisciplinar en el entorno clínico español.

INTRODUCTION: malnutrition is a very frequent problem in oncology patients and can have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. OBJECTIVE: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. METHODS: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. RESULTS: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. CONCLUSIONS: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Social disparities in flood exposure and associations with the urban environment in 44,698 neighborhoods in 276 cities in eight Latin American countries.

Background: Climate change is expected to greatly increase exposure to flooding, particularly in urban populations in low- and middle-income countries. We examined within-city social disparities in exposure to flooding in 276 Latin American cities and associated features of the neighborhood urban environment. Methods: We used a spatially granular dataset of historical flood events from 2000 to 2018 to describe neighborhood flooding within cities across eight Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Guatemala, Mexico, and Panama). We estimated the percentage of the population living in flooded neighborhoods, described social disparities in flooding based on neighborhood educational attainment, and compared the magnitude of disparities across and within cities. We used multilevel models to examine how city- and neighborhood-level factors are related to neighborhood flooding. Results: We examined 44,698 neighborhoods in 276 cities from eight countries with a total of 223 million residents and 117 distinct flood events from 2000-2018. One in four residents in neighborhoods in the lowest education quintile lived in neighborhoods with flooding, compared to one in 20 residents of the highest neighborhood education quintile. Greater neighborhood flooding was associated with lower neighborhood-level educational attainment and with neighborhoods that were coastal, less dense (population or intersection), further from the city center, greener, and had steeper slopes. There was no association between city-level educational attainment and flooding. Conclusion: There are large social disparities in neighborhood flooding within Latin American cities. Residents of areas with lower education attainment face substantially higher risks of flooding. Policymakers must prioritize flood adaptation and recovery efforts in neighborhoods with lower socioeconomic position.

A case-cohort study of per- and polyfluoroalkyl substance concentrations and incident prostate cancer in the cancer prevention Study-II LifeLink cohort study.

INTRODUCTION: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potentially carcinogenic chemicals. Previous studies investigating PFAS exposure and prostate cancer yielded mixed findings. We aimed to investigate associations between PFAS exposure and incident prostate cancer in a large cohort of U.S. men, overall and by selected demographic, lifestyle, and medical-related characteristics. METHODS: We conducted a case-cohort study among Cancer Prevention Study-II LifeLink Cohort participants who, at baseline (1998-2001), had serum specimens collected and no prior cancer diagnosis. The study included all men diagnosed with prostate cancer (n = 1610) during follow-up (baseline-June 30, 2015) and a random sub-cohort of 500 men. PFAS concentrations [perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorooctanoic acid (PFOA)] were measured in stored serum specimens. We used multivariable Cox proportional hazards models to estimate associations between PFAS concentrations and prostate cancer, overall and by selected characteristics (grade, stage, family history, age, education, smoking status, and alcohol consumption). RESULTS: Prostate cancer hazards were slightly higher among men with concentrations in the highest (Q4) vs lowest quartile (Q1) for PFHxS [hazard ratio (HR) (95% CI): 1.18 (0.88-1.59)] and PFOS [HR (95% CI): 1.18 (0.89-1.58)], but not for PFNA or PFOA. However, we observed heterogeneous associations by age, family history of prostate cancer (PFHxS), alcohol consumption (PFHxS), and education (PFNA). For example, no meaningful associations were observed among men aged <70 years at serum collection, but among men aged ≥70 years, HRs (95% CIs) comparing Q4 to Q1 were PFHxS 1.54 (1.02-2.31) and PFOS 1.62 (1.08-2.44). No meaningful heterogeneity in associations were observed by tumor grade or stage. CONCLUSIONS: Our findings do not clearly support an association between the PFAS considered and prostate cancer. However, positive associations observed in some subgroups, and consistently positive associations observed for PFHxS warrant further investigation.

Closing the Sex-Based Differences in Stroke Care: Insights from a Large Telestroke Network on Treatment and Postacute Management.

Background: The evolution of ischemic stroke is different accordin'g to sex and is one of the main causes of death in women. Previous studies have shown that women are less likely to receive acute treatment, and stroke center type is an important predictor of door-to-needle times. We investigated whether women are attended in a similar way to men in the telestroke network with specialized stroke physicians. Methods: A prospective registry of ischemic strokes recorded in the centralized Andalusian telestroke network was analyzed, focusing on sex differences. Demographic data, clinical characteristics, neuroimaging data, treatment intervals, follow-up visits, and clinical outcomes were collected. Results: A total of 3009 suspected stroke patients were attended to in the telestroke network from 2019 to 2023, of which 42.74% were women. Women were older (p < 0.001) and less independent upon arrival (p = 0.006) than men. There was no difference in the treatment received or in the treatment time intervals between the groups. Importantly, there was no difference in modified Rankin scale scores at 3 months between sexes. At 3 months post-stroke follow-up, women had fewer imaging tests (p = 0.018) and fewer outpatient visits (p < 0.001) than men. Conclusions: No significant difference between men and women has been found in the acute treatment of stroke in a large telestroke network. However, the same is not true for the follow-up and management of patients after the acute phase. This fact supports that strict adherence to protocols and specialization of care lead to equal care that avoids sex differences in stroke treatment and functional outcomes.

Swine farm environmental microbiome: exploring microbial ecology and functionality across farms with high and low sanitary status.

Introduction: Stringent regulations in pig farming, such as antibiotic control and the ban on certain additives and disinfectants, complicate disease control efforts. Despite the evolution of microbial communities inside the house environment, they maintain stability over the years, exhibiting characteristics specific to each type of production and, in some cases, unique to a particular company or farm production type. In addition, some infectious diseases are recurrent in specific farms, while other farms never present these diseases, suggesting a connection between the presence of these microorganisms in animals or their environment. Therefore, the aim of this study was to characterise environmental microbiomes of farms with high and low sanitary status, establishing the relationships between both, health status, environmental microbial ecology and its functionality. Methods: For this purpose, 6 pig farms were environmentally sampled. Farms were affiliated with a production company that handle the majority of the pigs slaughtered in Spain. This study investigated the relationship among high health and low health status farms using high throughput 16S rRNA gene sequencing. In addition, to identify ecologically relevant functions and potential pathogens based on the 16S rRNA gene sequences obtained, functional Annotation with PROkaryotic TAXa (FAPROTAX) was performed. Results and Discussion: This study reveals notable differences in microbial communities between farms with persistent health issues and those with good health outcomes, suggesting a need for protocols tailored to address specific challenges. The variation in microbial populations among farms underscores the need for specific and eco-friendly cleaning and disinfection protocols. These measures are key to enhancing the sustainability of livestock farming, ensuring safer products and boosting competitive edge in the market.

Tau protein profiling in tauopathies: a human brain study.

Abnormal accumulation of misfolded and hyperphosphorylated tau protein in brain is the defining feature of several neurodegenerative diseases called tauopathies, including Alzheimer's disease (AD). In AD, this pathological change is reflected by highly specific cerebrospinal fluid (CSF) tau biomarkers, including both phosphorylated and non-phosphorylated variants. Interestingly, despite tau pathology being at the core of all tauopathies, CSF tau biomarkers remain unchanged in certain tauopathies, e.g., progressive supranuclear palsy (PSP), Pick's disease (PiD), and corticobasal neurodegeneration (CBD). To better understand commonalities and differences between tauopathies, we report a multiplex assay combining immunoprecipitation and high-resolution mass spectrometry capable of detecting and quantifying peptides from different tau protein isoforms as well as non-phosphorylated and phosphorylated peptides, including those carrying multiple phosphorylations. We investigated the tau proteoforms in soluble and insoluble fractions of brain tissue from subjects with autopsy-confirmed tauopathies, including sporadic AD (n = 10), PSP (n = 11), PiD (n = 10), and CBD (n = 10), and controls (n = 10). Our results demonstrate that non-phosphorylated tau profiles differ across tauopathies, generally showing high abundance of microtubule-binding region (MTBR)-containing peptides in insoluble protein fractions compared with controls; the AD group showed 12-72 times higher levels of MTBR-containing aggregates. Quantification of tau isoforms showed the 3R being more abundant in PiD and the 4R isoform being more abundant in CBD and PSP in the insoluble fraction. Twenty-three different phosphorylated peptides were quantified. Most phosphorylated peptides were measurable in all investigated tauopathies. All phosphorylated peptides were significantly increased in AD insoluble fraction. However, doubly and triply phosphorylated peptides were significantly increased in AD even in the soluble fraction. Results were replicated using a validation cohort comprising AD (n = 10), CBD (n = 10), and controls (n = 10). Our study demonstrates that abnormal levels of phosphorylation and aggregation do indeed occur in non-AD tauopathies, however, both appear pronouncedly increased in AD, becoming a distinctive characteristic of AD pathology.

Bronquitis plástica. Caso clínico interesante / Plastic Bronchitis. Interesting Case Report

La bronquitis plástica es una enfermedad infrecuente y poco estudiada. Se caracteriza por la obstrucción parcial o total de la vía aérea inferior por moldes o yesos gomosos y firmes, compuestos por múltiples sustancias como fibrina, mucina y otros, que se acumulan en la luz bronquial. En la actualidad, no hay un consenso de la fisiopatología real. Puede presentarse con síntomas leves como tos, sibilancias y disnea, hasta eventos fatales de insuficiencia respiratoria. Se clasifican en tipo I (inflamatorios) y tipo II (acelulares). La presencia de la bronquitis plástica es una complicación de varias enfermedades y está relacionada con procedimientos correctivos de cardiopatías congénitas (procedimiento de Fontan). El diagnóstico se hace a través de la identificación de los yesos bronquiales, ya sea cuando el paciente los expectora o por broncoscopía. Se han utilizado múltiples terapias que solo tienen evidencias anecdóticas. En los últimos años se han observado buenos resultados con el uso de heparinas, así como el alteplasa nebulizado e instilado por broncoscopia.

Plastic bronchitis is a rare and little-studied disease. It is characterized by partial or total obstruction of the lower airway by rubbery and firm molds or plasters, made up of multiple substances that accumulate in the bronchial lumen. Currently, there is no consensus on real pathophysiology. It can present itself with mild symptoms such as cough, wheezing and dyspnea, to fatal events of respiratory failure. They are classified into type I (inflammatory) and type II (acellular). The presence of plastic bronchitis is a complication of several diseases and in corrective procedures for congenital heart disease (Fontan procedure). Diagnosis is made by identifying bronchial casts, either by the patient expectorating them or by bronchoscopy. Multiple therapies have been used that only have anecdotal evidence. In recent years, good results have been observed with the use of heparins and tPA nebulized and instilled by bronchoscop.

Assessing Diagnosis of Candida Infections: A Study on Species Prevalence and Antifungal Resistance in Northern Morocco.

The incidence of Candida infections has increased in the last decade, posing a serious threat to public health. Appropriately facing this challenge requires precise epidemiological data on species and antimicrobial resistance incidence, but many countries lack appropriate surveillance programs. This study aims to bridge this gap for Morocco by identifying and phenotyping a year-long collection of clinical isolates (n = 93) from four clinics in Tetouan. We compared the current standard in species identification with molecular methods and assessed susceptibility to fluconazole and anidulafungin. Our results identified limitations in currently used diagnostics approaches, and revealed that C. albicans ranks as the most prevalent species with 60 strains (64.52%), followed by C. glabrata with 14 (15.05%), C. parapsilosis with 6 (6.45%), and C. tropicalis with 4 (4.30%). In addition, we report the first identification of C. metapsilosis in Morocco. Susceptibility results for fluconazole revealed that some isolates were approaching MICs resistance breakpoints in C. albicans (2), and C. glabrata (1). Our study also identified anidulafungin resistant strains in C. albicans (1), C. tropicalis (1), and C. krusei (2), rendering the two strains from the latter species multidrug-resistant due to their innate resistance to fluconazole. These results raise concerns about species identification and antifungal resistance in Morocco and highlight the urgent need for more accurate methods and preventive strategies to combat fungal infections in the country.

Spark-Discharge-Activated 3D-Printed Electrochemical Sensors.

3D printing technology is a tremendously powerful technology to fabricate electrochemical sensing devices. However, current conductive filaments are not aimed at electrochemical applications and therefore require intense activation protocols to unleash a suitable electrochemical performance. Current activation methods based on (electro)chemical activation (using strong alkaline solutions and organic solvents and/or electrochemical treatments) or combined approaches are time-consuming and require hazardous chemicals and dedicated operator intervention. Here, pioneering spark-discharge-activated 3D-printed electrodes were developed and characterized, and it was demonstrated that their electrochemical performance was greatly improved by the effective removal of the thermoplastic support polylactic acid (PLA) as well as the formation of sponge-like and low-dimensional carbon nanostructures. This reagent-free approach consists of a direct, fast, and automatized spark discharge between the 3D-electrode and the respective graphite pencil electrode tip using a high-voltage power supply. Activated electrodes were challenged toward the simultaneous voltammetric determination of dopamine (DP) and serotonin (5-HT) in cell culture media. Spark discharge has been demonstrated as a promising approach for conductive filament activation as it is a fast, green (0.94 GREEnness Metric Approach), and automatized procedure that can be integrated into the 3D printing pipeline.

The effectiveness of cognitive behavioral therapy for insomnia on sleep outcomes in the context of pain among older adult veterans.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is the gold-standard treatment for insomnia disorder in adults. Compared to young adults, older adults have increased risk for the development of conditions associated with chronic pain, which may impact the efficacy of CBT-I in improving insomnia symptoms in older adults. This study evaluated the effect of participant-rated pain on sleep-related outcomes of a supervised, non-clinician administered CBT-I program in older adult patients with chronic insomnia disorder. METHODS: Secondary analysis was conducted using data from a randomized controlled trial among 106 community-dwelling older adult veterans (N = 106; mean age 72.1 years, 96% male, 78.3% White, 6.6% Hispanic, 5.7% African American) with chronic (≥3 months) insomnia disorder. Participants engaged in five sessions of manual-based CBT-I in individual or group format within one Department of Veterans Affairs healthcare system, provided by non-clinician "sleep coaches" who had weekly telephone supervision by behavioral sleep medicine specialists. Insomnia symptoms (Insomnia Severity Index), perceived sleep quality (Pittsburgh Sleep Quality Index), fatigue (Flinder's Fatigue Scale), daytime sleepiness (Epworth Sleepiness Scale), and perceived pain severity (items from the Geriatric Pain Measure) were assessed at 4 time points: baseline, one-week posttreatment, 6-month follow-up, and 12-month follow-up. Mixed effects models with time invariant and time varying predictors were employed for analyses. RESULTS: CBT-I improved insomnia symptoms, perceived sleep quality, fatigue, and daytime sleepiness among older veterans with chronic insomnia. Participant-reported pain was associated with greater improvements in insomnia symptoms following CBT-I. Pain did not affect improvements in other sleep-related outcomes (-0.38 ≤ b ≤ 0.07, p > 0.05). Between-subjects differences in pain, but not within-subject changes in pain over time, appeared to play a central role in insomnia symptom improvement at posttreatment, with individuals with higher-than-average pain showing greater insomnia symptom improvement (ISI score reduction; -0.32 ≤ b ≤ -0.28, p ≤ 0.005). CONCLUSIONS: Pain did not meaningfully hinder the effects of CBT-I on sleep outcomes. Among older veterans with chronic insomnia disorder, individuals with higher pain exhibited slightly greater improvement in insomnia than those with lower levels of pain. These findings suggest that experiencing pain does not impair treatment response and should not preclude older adults with insomnia from being offered CBT-I.

Tirofiban versus aspirin to prevent in-stent thrombosis after emergent carotid artery stenting in acute ischemic stroke.

BACKGROUND: Several antithrombotic treatments during emergent carotid artery stenting (eCAS) have been proposed, but an appropriate protocol to balance risk-benefit is not well known. OBJECTIVE: To investigate the efficacy and safety of tirofiban compared with aspirin in patients with acute ischemic stroke undergoing eCAS. METHODS: We conducted a retrospective single-center study of the prospective ARTISTA Registry, including patients with atherosclerotic internal carotid artery occlusion treated with eCAS. Two groups, according to antiplatelet drug, were studied: aspirin (250-500 mg single-dose) versus tirofiban (500 µg bolus+200 µg/h). Primary outcomes were the rate of in-stent thrombosis and symptomatic intracranial hemorrhage (sICH) within the first 24 hours. RESULTS: During the period 2019-2023, 181 patients were included, 103 received aspirin, 78 tirofiban; 149 (82.3%) had tandem lesions. The primary efficacy outcome occurred in 9 (9.4%) in the aspirin group, as compared with 1 (1.3%) in the tirofiban group (adjusted odds ratio (aOR)=0.11, 95% CI 0.01 to 0.98; P=0.048). The primary safety outcome was detected in 12 (11.7%) in the aspirin group, as compared with 2 (2.6%) in the tirofiban group (aOR=0.16, 95% CI 0.03 to 0.87; P=0.034). The tirofiban group presented a lower risk of parenchymal hemorrhage (18 (17.4%) vs 4 (5.2%), aOR=0.27, 95% CI 0.09 to 0.88; P=0.029) and an increased rate of excellent recanalization (expanded Treatment in Cerebral Infarction (eTICI) 2c-3) (50 (48.5%) vs 54 (69.2%); aOR=2.15, 95% CI 1.12 to 4.13; P=0.02). There were no differences in functional outcomes or mortality at 3 months. CONCLUSIONS: Periprocedural antithrombotic therapy with tirofiban was associated with a lower risk of in-stent thrombosis and sICH at 24 hours from eCAS compared with aspirin. Prospective randomized clinical trials are needed to confirm our results.

Synergistic impact of innate immunity hyper-activation and endothelial dysfunction on the magnitude of organ failure in the infection-sepsis continuum.

OBJECTIVES: Identifying host response biomarkers implicated in the emergence of organ failure during infection is key to improving the early detection of this complication. METHODS: Twenty biomarkers of innate immunity, T-cell response, endothelial dysfunction, coagulation, and immunosuppression were profiled in 180 surgical patients with infections of diverse severity (IDS) and 53 with no infection (nIDS). Those better differentiating IDS/nIDS in the area under the curve were combined to test their association with the sequential organ failure assessment score by linear regression analysis in IDS. Results were validated in another IDS cohort of 174 patients. RESULTS: C-reactive protein, procalcitonin, pentraxin-3, lipocalin-2 (LCN2), tumoral necrosis factor-α, angiopoietin-2, triggering receptor expressed on myeloid cells-1 (TREM-1) and interleukin (IL)-15 yielded an area under the curve ≥0.75 to differentiate IDS from nIDS. The combination of LCN2, IL-15, TREM-1, angiopoietin-2 (Dys-4) showed the strongest association with sequential organ failure assessment score in IDS (adjusted regression coefficient; standard error; P): Dys-4 (3.55;0.44; <0.001), LCN2 (2.24; 0.28; <0.001), angiopoietin-2 (1.92; 0.33; <0.001), IL-15 (1.78; 0.40; <0.001), TREM-1(1.74; 0.46; <0.001), tumoral necrosis factor-α (1.60; 0.31; <0.001), pentraxin-3 (1.12; 0.18; <0.001), procalcitonin (0.85; 0.12; <0.001). Dys-4 provided similar results in the validation cohort. CONCLUSIONS: There is a synergistic impact of innate immunity hyper-activation (LCN2, IL-15, TREM-1) and endothelial dysfunction (angiopoietin-2) on the magnitude of organ failure during infection.

Insights into the Window of Opportunity and Outcome Measures in Patients with Moderate to Severe Hidradenitis Suppurativa Treated with Secukinumab: A Real-World Study.

INTRODUCION: The concept of a window of opportunity in hidradenitis suppurativa (HS) management suggests that early initiation of biological therapy leads to better outcomes, though its timing remains uncertain. METHODS: We conducted a retrospective observational multicenter study, including consecutive patients with moderate to severe HS who initiated secukinumab treatment following prior failure with systemic antibiotics or adalimumab. Therapeutic burden was defined as the sum of previous systemic treatment cycles and previous major surgical interventions for HS. Patients were followed up for 24 weeks. Main outcomes were safety and effectiveness, assessed through the proportion of patients achieving HS Clinical Response (HiSCR) and a 55% reduction in International HS Severity Score System (IHS4-55). Additionally, potential predictors of response to secukinumab were studied. Analysis was performed on an intention-to-treat basis. RESULTS: A total of 67 patients (33 men, 34 women) were included, with a mean age of 41.55 (11.94) years and a mean baseline IHS4 of 17.88 (11.13). The mean therapeutic burden was 6.06 (3.49). At week 24, 10.45% (7/67) of patients experienced adverse events, with three leading to treatment discontinuation. At week 24, 41.79% (28/67) of patients achieved HiSCR, and 44.78% (30/67) of patients achieved IHS4-55. HiSCR could not be calculated in 12 patients with a baseline AN count < 3. A lower therapeutic burden was significantly associated with a higher likelihood of achieving HiSCR and IHS4-55 at week 24. CONCLUSIONS: Secukinumab showed safety and efficacy in real-world patients with HS, and the inverse correlation found between therapeutic burden and treatment response supports the concept of a window of opportunity, offering insights into its timing.

Case report: A novel somatic SDHB variant in a patient with bladder paraganglioma.

Background: Paragangliomas (PGL) are rare neuroendocrine tumors derived from the autonomic nervous system paraganglia. Urinary bladder paragangliomas (UBPGL) originate from the sympathetic neurons of the urinary bladder wall and represent 0.7% of all paragangliomas and <0.05% of all bladder tumors. PGL and UBPGL can be associated with SDHB, SDHD, NF1, and VHL gene variants, with the most common germline alterations found in SDHB and VHL. Case report: We report a case of a 42-year-old woman who presented with menorrhagia/hematuria, uterine leiomyomas, as well as cardiac and bladder masses. The cardiac mass was favored to be a myxoma based on clinical findings, while the bladder mass was diagnosed as UBPGL. A novel SDHB mutation (c.642G>A, p Q214Q), detected in the UBPGL, was proven to be somatic. Although this variant was seemingly synonymous, it was predicted to have a loss of function due to the splice site effect, which was further supported by the immunohistochemical loss of SDHB. Conclusion: This case highlights the challenges of diagnosing an extremely rare entity, bladder paraganglioma, with an emphasis on the multidisciplinary approach to navigate various clinical and imaging findings that may initially be misleading. In addition, a novel loss of function SDHB variant that could have been overlooked as a synonymous variant is herein reported, while also illustrating the importance of both germline and somatic mutation testing.