Loop diuretic down-titration at discharge in patients hospitalized for acute heart failure.

AIMS: The current literature provides limited guidance on the best diuretic strategy post-hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes. METHODS AND RESULTS: It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down-titration group and (ii) the stable/up-titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all-cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78-92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down-titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86-2.06, P = 0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125. CONCLUSIONS: In patients hospitalized for AHF, furosemide down-titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down-titration on the outcome. In patients with severe congestion or residual congestion at discharge, down-titration was associated with an increased risk of mortality and/or heart failure readmission.

Dysregulation in CD39/CD73 Axis May Trigger the Upsurge of the Immune Suppressive Agent Adenosine in OSA Patients.

INTRODUCTION: Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Interestingly, adenosinergic signaling has emerged as a powerful immune checkpoint driving tumor development and progression. METHODS: Here, we explored the expression of the adenosinergic ecto-enzymes CD39 and CD73 in T-lymphocytes of OSA patients without any evidence of cancer, as well as their soluble forms in plasma (sCD39 and sCD73), along with adenosine. In addition, we explored the role of intermittent hypoxia (IH) in this context by in vitro models. RESULTS: Our results showed that CD39 is upregulated while CD73 is downregulated in OSA T-cells' membrane. Moreover, our findings suggest that IH, through HIF-1, mediates the upregulation of both CD39 and CD73; and that CD73 downregulation could be mediated by a higher release of sCD73 by OSA T-lymphocytes. Importantly, we found that both sCD39 and sCD73 are upregulated in OSA plasma, suggesting T-lymphocytes as a potential source for plasmatic sCD73. Finally, our data propose the alterations in CD39/CD73 axis could underlie the upsurge of adenosine levels in the plasma of OSA patients. CONCLUSION: Our study reveals a hypoxia-mediated alteration of the CD39/CD73 axis in OSA patients, which could trigger ADO upregulation, thus potentially contributing to the immune suppressive environment and ultimately facilitating tumor development and progression. Therefore, our data highlights the need for new longitudinal studies evaluating CD39 and/or CD73 as potential cancer-risk prognostic biomarkers in OSA patients.

Special considerations for the adolescent with obesity: An obesity medicine association (OMA) clinical practice statement (CPS) 2024.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details special considerations for the management of the adolescent with obesity. The information in this CPS is based on scientific evidence, supported by medical literature, and derived from the clinical experiences of members of the OMA. Methods: The scientific information and clinical guidance in this CPS are based on scientific evidence, supported by the medical literature, and derived from the clinical perspectives of the authors. Results: This OMA Clinical Practice Statement addresses special considerations in the management and treatment of adolescents with overweight and obesity. Conclusions: This OMA Clinical Practice Statement on the adolescent with obesity is an overview of current recommendations. These recommendations provide a roadmap to the improvement of the health of adolescents with obesity, especially those with metabolic, physiological, and psychological complications. This CPS also addresses treatment recommendations and is designed to help the provider with clinical decision making.

Real-world effectiveness and persistence of secukinumab in the treatment of patients with psoriatic arthritis.

Introduction: Psoriatic arthritis (PsA) is a complex and heterogeneous inflammatory disease. Secukinumab, a biologic disease-modifying antirheumatic drug (bDMARD), has extensive clinical evidence of efficacy and safety in the treatment of PsA but data in clinical practice are still limited. This study aims to provide real-world evidence on secukinumab use, effectiveness, and persistence in PsA. Methods: A retrospective, multicenter study was conducted on patients diagnosed with PsA and treated with secukinumab up to June 2021 at 12 centers in the Valencian Community (Spain). Data on DAS28-CRP, DAPSA, Tender and Swollen Joint Counts (TJC, SJC), enthesitis, dactylitis, skin and nail involvement, pain, patient and physician global assessment (ptGA, phGA) using 100-mm visual analog scale (VAS), and persistence for up to 24 months were collected. Results: A total of 178 patients were included (49% men; mean [standard deviation, SD] age: 51.4 [10.5] years; 39% obese). Secukinumab was used as a first-, second-, or ≥ third-line bDMARD in 37, 21, and 42% of patients, respectively. The percentage of patients achieving at least low disease activity (DAS28-CRP ≤ 3.2) increased from 25% at baseline to 66% at month 6 (M6) and was maintained (75%) up to M24. Mean (SD) DAS28-CRP baseline values (3.9 [1.2]) decreased to 2.9 (1.1) (p < 0.001) at M6 and remained low through M24 (2.6 [1.1]) (p < 0.001). Secukinumab also improved peripheral arthritis increasing the percentage of patients with TJC = 0 (20% baseline; 57% M24) and SJC = 0 (37% baseline; 80% M24). Treatment reduced the percentage of patients with enthesitis (25% baseline; 6% M24), dactylitis (20% baseline; 4% M24), and skin (70% baseline; 17% M24), and nail (32% baseline; 2% M24) involvement. Additionally, we observed improvements in the mean pain VAS (-26.4 mm M24), ptGA (-26.2 mm M24), and phGA (-24.8 mm M24). Secukinumab showed an overall 24-month persistence rate of 67% (95% confidence interval [CI]: 60-74%). Patients receiving first-line secukinumab showed the highest 24-month persistence rate (83, 95% CI: 73-92; p = 0.024). Conclusion: Secukinumab showed long-term effectiveness across the six key PsA domains thus reducing disease activity and pain, which are major treatment goals. This was accompanied by high persistence rates, especially in bDMARD naive patients.

Assessment of Adverse Childhood Experiences and Social Determinants of Health: A Survey of Practices in Pediatric Weight Management Programs.

Introduction: Adverse childhood experiences (ACEs) and social determinants of health (SDoH) are associated with increased incidence of pediatric obesity. Recent literature highlights an imperative need to assess ACEs and SDoH among youth and families with obesity to identify those individuals requiring targeted interventions. The primary objective of the present study was to examine the frequency, methodology, and barriers in evaluation of ACEs and SDoH within pediatric weight management programs (PWMPs). Methods: Invitations were e-mailed to a comprehensive directory of 92 PWMPs in the United States with a link to complete an electronic survey. Results: Forty-one PWMPs from 26 states completed the survey. Assessment of one or more ACEs and SDoH was common and typically took place during the initial patient visit by the psychologist or medical practitioner through unstructured conversations. Reported barriers to assessment included lack of time to assess and to follow-up, lack of clinic protocols, and inadequate referral resources. Programs offering bariatric surgery and those with embedded mental health clinicians reported fewer barriers to ACEs/SDoH referral resources, while family-based and healthy lifestyle-focused programs perceived more barriers related to insufficient support staff and time to follow-up with families. Conclusions: Most PWMPs assess a subset of ACEs and SDoH; however, approaches to assessment vary, are often unstructured, and several barriers remain to optimizing assessment and follow-up. Future research should evaluate standardized ACEs/SDoH assessment protocols, ideal workflow, and their impact on obesity treatment and related health outcomes.

Kinetic and Parametric Analysis of the Separation of Ultra-Small, Aqueous Superparamagnetic Iron Oxide Nanoparticle Suspensions under Quadrupole Magnetic Fields.

Superparamagnetic iron oxide nanoparticles (SPIONs) have gathered tremendous scientific interest, especially in the biomedical field, for multiple applications, including bioseparation, drug delivery, etc. Nevertheless, their manipulation and separation with magnetic fields are challenging due to their small size. We recently reported the coupling of cooperative magnetophoresis and sedimentation using quadrupole magnets as a promising strategy to successfully promote SPION recovery from media. However, previous studies involved SPIONs dispersed in organic solvents (non-biocompatible) at high concentrations, which is detrimental to the process economy. In this work, we investigate, for the first time, the magnetic separation of 20 nm and 30 nm SPIONs dispersed in an aqueous medium at relatively low concentrations (as low as 0.5 g·L-1) using our custom, permanent magnet-based quadrupole magnetic sorter (QMS). By monitoring the SPION concentrations along the vessel within the QMS, we estimated the influence of several variables in the separation and analyzed the kinetics of the process. The results obtained can be used to shed light on the dynamics and interplay of variables that govern the fast separation of SPIONs using inexpensive permanent magnets.

Cutaneotrichosporon curvatum and Yarrowia lipolytica as key players for green chemistry: efficient oil producers from food waste via the carboxylate platform.

Cutaneotrichosporon curvatum and Yarrowia lipolytica can accumulate microbial oils using short-chain fatty acids (SCFA) as carbon sources. SCFAs-rich media often contain significant amounts of nitrogen that prevent high carbon:nitrogen (C:N) ratios necessary to boost lipid production. This work assessed the intrinsic ability of C. curvatum and Y. lipolytica to produce high amounts of microbial oils from these unusual carbon sources. Results demonstrated that minor differences in SCFA concentration (only 2 g/L) had a significant effect on yeast growth and lipid production. A C:N of 80 promoted yeast growth at all SCFA concentrations and favored SCFA consumption at 19 g/L SCFAs. The different SCFA uptake preferences in C. curvatum and Y. lipolytica highlighted the importance of considering the SCFA profile to select a suitable yeast strain for microbial oils production. At the most challenging SCFA concentration (19 g/L), 57.2% ±1.6% (w/w) and 78.4 ± 0.6% (w/w) lipid content were obtained in C. curvatum and Y. lipolytica, respectively. These values are among the highest reported for wild-type strains. To circumvent the challenges associated with media with high nitrogen content, this report also proved struvite precipitation as an effective method for increasing lipid production (from 17.9 ± 3.9% (w/w) to 41.9 ± 2.6% (w/w)) after nitrogen removal in food waste-derived media.

Slight variations in SCFA concentrations have a relevant effect on yeast lipid productionHigh nitrogen availability is crucial to promote cell growth at very high SCFA concentrationsC:N effect on cell growth and lipid production is specie-specific and may depend on yeast robustnessYeast strains have diverse SCFA preferences and differently metabolize these acidsStruvite precipitation effectively removes nitrogen from real digestates increasing C:N.

Chronic rhinosinusitis with nasal polyps and allergic rhinitis as different multimorbid treatable traits in asthma.

Background: Respiratory multimorbidities are linked to asthma, such as allergic rhinitis (AR) with early allergic asthma and chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) with late nonallergic asthma. Objective: Our aim was to investigate the association of asthma severity and control with specific upper airway phenotypes. Method: Patients with asthma were prospectively recruited from 23 pulmonology and ear, nose, and throat clinics. Asthma severity and control, as well as upper airway comorbidities (AR and non-AR [NAR], CRSwNP, and CRS without nasal polyps [CRSsNP]) were assessed according to international consensus guidelines definitions. Results: A total of 492 asthmatic patients were included. Half of the asthmatic patients (49.6%) had associated rhinitis (37.0% had AR and 12.6% had NAR) and 36.2% had CRS (16.7% had CRSsNP and 19.5% had CRSwNP), whereas 14.2% had no sinonasal symptoms. Most cases of AR (78%) and NAR (84%) were present in patients with mild-to-moderate asthma, whereas CRSwNP was more frequent in patients with severe asthma (35% [P < .001]), mainly nonatopic asthma (44% [P < .001]). Patients with severe asthma with CRSwNP had worse asthma control, which was correlated (r = 0.249 [P = .034]) with sinus occupancy. Multiple logistic regression analysis showed that late-onset asthma, intolerance of aspirin and/or nonsteroidal anti-inflammatory drugs, and CRSwNP were independently associated with severe asthma. Conclusion: Severe asthma is associated with CRSwNP, with sinus occupancy affecting asthma control. This study has identified 2 main different upper airway treatable traits, AR and CRSwNP, which need further evaluation to improve management and control of patients with asthma.

PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea.

Introduction: Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy. Methods: The expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using in vitro models. In addition, PSGL-1 impact on T-cells function was evaluated by ex vivo models. Results: Data showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia. Discussion: In conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.

Efficacy of a synthetic peptide Chlamydia pecorum major outer membrane protein vaccine in a wild koala (Phascolarctos cinereus) population.

Chlamydiosis is a significant disease affecting Eastern Australian koala (Phascolarctos cinereus) populations, impacting individual animal welfare and fecundity and therefore influencing population dynamics. The aim of this study was to investigate the effect of a synthetic peptide vaccine based on 4 components of the Chlamydia pecorum major outer membrane protein (MOMP), over an 18-month period in a koala population severely impacted by chlamydiosis. Wild koalas were recruited into a vaccination or a placebo treatment group on a random allocation, then followed through a period of 18 months, with recapture at 6 monthly intervals. Vaccination did not alter clinical disease expression or chlamydial shedding from the ocular or urogenital sites. Vaccination did not stimulate a significant plasma anti-MOMP IgG response, when compared to the placebo group. There was no significant effect of vaccination on IFN-γ and IL-17A mRNA expression of peripheral blood lymphocytes when stimulated with rMOMP. We have demonstrated that a synthetic peptide vaccination against chlamydiosis is not an effective management tool in a koala population with a high prevalence of C. pecorum infection and related disease. The lack of antigenic response found in this study suggests that further research utilising a larger, full-length antigen is an avenue worth investigation if we are to consider vaccination as a part of a management strategy in diseased koala populations.

Predicting ICU Mortality in Acute Respiratory Distress Syndrome Patients Using Machine Learning: The Predicting Outcome and STratifiCation of severity in ARDS (POSTCARDS) Study.

OBJECTIVES: To assess the value of machine learning approaches in the development of a multivariable model for early prediction of ICU death in patients with acute respiratory distress syndrome (ARDS). DESIGN: A development, testing, and external validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: A total of 1,303 patients with moderate-to-severe ARDS managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed and tested prediction models in 1,000 ARDS patients. We performed logistic regression analysis following variable selection by a genetic algorithm, random forest and extreme gradient boosting machine learning techniques. Potential predictors included demographics, comorbidities, ventilatory and oxygenation descriptors, and extrapulmonary organ failures. Risk modeling identified some major prognostic factors for ICU mortality, including age, cancer, immunosuppression, Pa o2 /F io2 , inspiratory plateau pressure, and number of extrapulmonary organ failures. Together, these characteristics contained most of the prognostic information in the first 24 hours to predict ICU mortality. Performance with machine learning methods was similar to logistic regression (area under the receiver operating characteristic curve [AUC], 0.87; 95% CI, 0.82-0.91). External validation in an independent cohort of 303 ARDS patients confirmed that the performance of the model was similar to a logistic regression model (AUC, 0.91; 95% CI, 0.87-0.94). CONCLUSIONS: Both machine learning and traditional methods lead to promising models to predict ICU death in moderate/severe ARDS patients. More research is needed to identify markers for severity beyond clinical determinants, such as demographics, comorbidities, lung mechanics, oxygenation, and extrapulmonary organ failure to guide patient management.

Spontaneously ruptured hepatocellular carcinoma on non-cirrhotic liver: A prospective case series.

BACKGROUND AND AIMS: Spontaneous ruptured hepatocellular carcinoma is an uncommon complication, and there are scarce data about non-cirrhotic patients. Tumor treatment is not standardized and the risk of peritoneal dissemination is unclear. AIM: we analyzed the treatment and survival in patients with rHCC on non-cirrhotic liver. METHODS: One hundred and forty-one non-cirrhotic patients with hepatocellular carcinoma diagnosed by histology were included in a multicenter prospective registry (2018-2022). Seven of them (5%) presented with hemoperitoneum due to spontaneous rupture. RESULTS: Liver disease was associated in three patients (42.9%). A single nodule was detected in three cases (42.9%). One patient had vascular invasion and none extrahepatic spread. Initial hemostatic therapy and sequential treatment was individualized. Patients with single nodule were treated: resection (one case) with recurrence at 4 months treated with TACE and sorafenib. TACE/TAE followed by surgery (two cases) one in remission 43 months later, the other had liver recurrence at 18 months and was transplanted. Patients with multiple lesions were treated: TAE/emergency surgery and subsequent systemic therapy (two cases), one received lenvatinib (1-year survival) and the other sorafenib (5-month survival). TAE and surgery with subsequent systemic therapy (one case). Initial hemostatic surgery, dying on admission (one case). No patient developed intraperitoneal metastasis. All patients with multiple lesions died by tumor. The 3-year survival rate was 42.9%. CONCLUSIONS: Initial hemostasis was achieved in all patients by TAE/TACE or surgery. Subsequent treatment was individualized, based on tumor characteristics, regardless of rupture. Long-time remission could be achieved in single nodule patients.

[Organoleptic evaluation of a diabetes-specific oral nutritional supplement with extra virgin olive oil in patients at nutritional risk and type 2 diabetes mellitus: Double-blind, randomized, crossover and multicenter clinical trial (DIACARE)]. / Evaluación sensorial de un suplemento nutricional oral específico para diabetes con aceite de oliva virgen extra en pacientes en riesgo nutricional y diabetes mellitus tipo 2: ensayo clínico doble ciego, aleatorizado, cruzado y multicéntrico (DIACARE.

Introduction: Introduction: oral nutritional supplements specific for diabetes (DSF) usually have a composition that favors their palatability and simultaneous glycemic and metabolic control. Objetive: to compare the sensory acceptability of a DSF with respect to a standard oral nutritional supplement (STF) in patients at risk of malnutrition with type 2 diabetes mellitus. Method: randomized, double-blind, crossover, multicenter, controlled, double-blind clinical trial. Odor, taste and perceived texture of a DSF and a STD were evaluated using a scale of 1 to 4. Results: twenty-nine patients were recruited and 58 organoleptic evaluations of the supplements were registered. A better evaluation of DSF was observed with respect to STD, although no statistically significant differences were reached: odor, 0.04 (CI 95 %) -0.49 to 0.56 (p = 0.092); taste, 0.14 (CI 95 %), -0.35 to 0.63 (p = 0.561); texture, 0.14 (CI 95 %), -0.43 to 0.72 (p = 0.619). No differences were found when analyzed by order of randomization, sex, degree of malnutrition, greater or lesser degree of complexity, greater or lesser time of evolution of diabetes, or by being older or younger. Conclusions: the specific nutritional supplement for diabetic patients formulated with extra virgin olive oil, EPA and DHA, a specific mixture of carbohydrates, and fiber, presented an adequate sensory acceptance by malnourished patients with type 2 diabetes mellitus.

Introducción: Introducción: las fórmulas nutricionales específicas para diabetes (FED) suelen presentar una composición que favorece simultáneamente su palatabilidad y el control glucémico y metabólico. Objetivo: comparar la aceptación sensorial de un FED respecto a un suplemento nutricional oral estándar (FE) en pacientes en riesgo de desnutrición con diabetes mellitus tipo 2. Método: ensayo clínico, aleatorizado, doble ciego, cruzado, multicéntrico y controlado. Se evaluó, a través de una escala del 1 al 4, el olor, el sabor y la textura percibida de un FED y de un FE. Resultados: se reclutaron a 29 pacientes y 58 evaluaciones sensoriales de los suplementos. Se observó una mejor valoración de la FED respecto a la FE, aunque no se alcanzaron diferencias estadísticamente significativas: olor, 0,04 (IC 95 %), de -0,49 a 0,56 (p = 0,092); sabor, 0,14 (IC 95 %), de -0,35 a 0,63 (p = 0,561); textura, 0,14, (IC 95 %), de -0,43 a 0,72 (p = 0,619). No se encontraron diferencias cuando se analizaron por orden de aleatorización, sexo, grado de desnutrición, mayor o menor grado de complejidad, mayor o menor tiempo de evolución de la diabetes, ni por ser más o menos mayores. Conclusiones: el suplemento nutricional específico para paciente con diabetes, formulado con aceite de oliva virgen extra, EPA y DHA, una mezcla específica en hidratos de carbono, fibra soluble e insoluble, presentó una adecuada aceptación sensorial del paciente desnutrido con diabetes mellitus tipo 2.

Glycaemic and insulinaemic impact of a diabetes-specific oral nutritional supplement with extra-virgin olive oil in patients with type 2 diabetes mellitus at nutritional risk: a randomized, double-blind, crossover, multicentre clinical trial (DIACARE).

Introduction: Introduction: there is controversy about the usefulness of specific enteral nutrition formulas in malnourished patients with diabetes. The effects on blood glucose and other aspects of metabolic control are not fully understood in the scientific literature. Objective: the aim of the study was to compare the glycaemic and insulinaemic response of patients with type 2 diabetes at risk of malnutrition after oral feed between a diabetes-specific formula with AOVE (DSF) and a standard one (STF). Methods: A randomized, double-blind, crossover, multicentre clinical trial was conducted in patients with type 2 diabetes at risk of malnutrition (SGA). The patients were randomized to receive either DSF or STF, a week apart. A glycaemia and insulinaemia curve was made at times 0 minutes, 30 min, 60 min, 90 min, 120 min, and 180 min after the patients drank 200 ml of the oral nutritional supplement (ONS). The principal variables were the area under the curve (AUC0-t) of glucose and insulin. Results: 29 patients (51 % women) were included, who were on average 68.84 (SD 11.37) years old. Regarding the degree of malnutrition, 86.2 % presented moderate malnutrition (B) and 13.8 % severe (C). When the patients received the DSF, they had a lower mean of glucose AUC0-t (-3,325.34 mg/min/dl [95 % CI: -4,3608.34 to -2,290.07]; p = 0.016) and also a lower mean of insulin AUC0-t (-451.14 uU/min/ml [95 % CI: -875,10 to -27.17]; p = 0.038). There were no differences in the degree of malnutrition. Conclusion: compared with STF, DSF with AOVE showed a better glycaemic and insulinaemic response in patients with type 2 diabetes at risk of malnutrition.

Introducción: Introducción: la utilidad de las fórmulas específicas de nutrición enteral en el paciente desnutrido con diabetes resulta controvertida. Sus efectos sobre la glucosa en sangre y otros aspectos del control metabólico no se conocen del todo en la literatura científica. Objetivo: el objetivo del estudio fue comparar la respuesta glucémica e insulinémica de los pacientes con diabetes tipo 2 (DM2) en riesgo de desnutrición tras la ingesta oral de una fórmula específica para diabetes (DSF) con aceite de oliva virgen extra (AOVE) y una estándar (STF). Métodos: ensayo clínico aleatorizado, doble ciego, cruzado y multicéntrico enpacientes con DM2 en riesgo de desnutrición (SGA). Los pacientes se asignaron aleatoriamente para recibir DSF o STF con una semana de diferencia. Se realizó una curva de glucemia e insulinemia en los siguientes tiempos: 0 minutos, 30 min, 60 min, 90 min, 120 min y 180 min tras la ingesta de 200 ml del suplemento nutricional oral (SNO). Las variables principales fueron el área bajo la curva (AUC0-t) de glucosa e insulina. Resultados: se incluyeron 29 pacientes (51 % mujeres), con una edad media de 68,84 años (DE 11,37). En cuanto al grado de desnutrición, el 86,2 % presentaba desnutrición moderada (B) y el 13,8 %, severa (C). Cuando los pacientes recibieron DSF tuvieron una media más baja de AUC0-t de glucosa (-3325,34 mg/min/dl [IC 95 %: de -4.3608,34 a -2.290,07]; p = 0,016) y también una media más baja de AUC0-t de insulina (-451,14 uU/min/ml [IC 95 %: de -875,10 a -27,17]; p = 0,038) respecto a cuando recibieron STF. No hubo diferencias por el grado de desnutrición. Conclusión: la fórmula con AOVE específica para diabetes mostró una mejor respuesta glucémica e insulinémica en pacientes con diabetes tipo 2 en riesgo de desnutrición respecto a una fórmula estándar.

Preoperative Risk Factors for Adverse Events in Adults Undergoing Bowel Resection for Inflammatory Bowel Disease: 15-Year Assessment of the American College of Surgeons National Surgical Quality Improvement Program.

INTRODUCTION: Older adults with inflammatory bowel disease (IBD) are at higher risk for postoperative complications as compared to their younger counterparts; however, factors contributing to this are unknown. We assessed risk factors associated with adverse IBD-related surgical outcomes, evaluated trends in emergency surgery, and explored differential risks by age. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified adults ≥18 years of age who underwent an IBD-related intestinal resection from 2005 to 2019. Our primary outcome included a 30-day composite of mortality, readmission, reoperation, and/or major postoperative complication. RESULTS: Overall, 49,746 intestinal resections were performed with 9,390 (18.8%) occurring among older adults with IBD. Nearly 37% of older adults experienced an adverse outcome as compared to 28.1% among younger adults with IBD ( P < 0.01). Among all adults with IBD, the presence of preoperative sepsis (adjusted odds ratio [aOR], 2.08; 95% confidence interval [CI] 1.94-2.24), malnutrition (aOR, 1.22; 95% CI 1.14-1.31), dependent functional status (aOR, 6.92; 95% CI 4.36-11.57), and requiring emergency surgery (aOR, 1.50; 95% CI 1.38-1.64) increased the odds of an adverse postoperative outcome, with similar results observed when stratifying by age. Furthermore, 8.8% of surgeries among older adults were emergent, with no change observed over time ( P = 0.16). DISCUSSION: Preoperative factors contributing to the risk of an adverse surgical outcome are similar between younger and older individuals with IBD, and include elements such as malnutrition and functional status. Incorporating these measures into surgical decision-making can reduce surgical delays in older individuals at low risk and help target interventions in those at high risk, transforming care for thousands of older adults with IBD.

Venous thromboembolism characteristics, treatment and outcomes in young adults: findings from the Registro Informatizado de Enfermedad TromboEmbólica registry.

BACKGROUND: Venous thromboembolism (VTE) is rare in patients aged <21 years. Young adults aged 18 to 21 years are frequently included in adult VTE studies, whereas pediatric VTE studies include patients aged up to either 18 or 21 years. The clinical characteristics of young adult patients with VTE have not been well defined. OBJECTIVES: We aimed to highlight any unique characteristics or treatment considerations that may apply to young adult patients with VTE. METHODS: Data from the prospective, international Registro Informatizado de Enfermedad TromboEmbólica registry were used. Patients were stratified into subcohorts according to age. The clinical characteristics, risk factors, management, and outcomes of young adult patients with VTE were compared with those of adolescents aged 12 to 18 years and adults aged >21 years. RESULTS: Of 104 253 Registro Informatizado de Enfermedad TromboEmbólica patients enrolled until August 2022, 234 were adolescents and 884 were young adults. Less cases of pulmonary embolism were reported in adolescents (P < .001). Estrogen use was a common risk factor, more prevalent in adolescents and young adults (P < .001), whereas active cancer and immobilization were uncommon in both. Most patients were initially treated with low-molecular-weight heparin. VTE recurrence, major bleeding, and all-cause mortality rates were comparably low among adolescents and young adults. None of the patients aged <21 years died from VTE recurrence. CONCLUSION: Young adults have some distinctive VTE risk factors. While VTE presentation may be similar among young adults and older patients, the outcomes of patients aged <21 years are more favorable.

Neuroprotective and Disease-Modifying Effects of the Triazinetrione ACD856, a Positive Allosteric Modulator of Trk-Receptors for the Treatment of Cognitive Dysfunction in Alzheimer's Disease.

The introduction of anti-amyloid monoclonal antibodies against Alzheimer's disease (AD) is of high importance. However, even though treated patients show very little amyloid pathology, there is only a modest effect on the rate of cognitive decline. Although this effect can possibly increase over time, there is still a need for alternative treatments that will improve cognitive function in patients with AD. Therefore, the purpose of this study was to characterize the triazinetrione ACD856, a novel pan-Trk positive allosteric modulator, in multiple models to address its neuroprotective and potential disease-modifying effects. The pharmacological effect of ACD856 was tested in recombinant cell lines, primary cortical neurons, or animals. We demonstrate that ACD856 enhanced NGF-induced neurite outgrowth, increased the levels of the pre-synaptic protein SNAP25 in PC12 cells, and increased the degree of phosphorylated TrkB in SH-SY5Y cells. In primary cortical neurons, ACD856 led to increased levels of phospho-ERK1/2, showed a neuroprotective effect against amyloid-beta or energy-deprivation-induced neurotoxicity, and increased the levels of brain-derived neurotrophic factor (BDNF). Consequently, administration of ACD856 resulted in a significant increase in BDNF in the brains of 21 months old mice. Furthermore, repeated administration of ACD856 resulted in a sustained anti-depressant effect, which lasted up to seven days, suggesting effects that go beyond merely symptomatic effects. In conclusion, the results confirm ACD856 as a cognitive enhancer, but more importantly, they provide substantial in vitro and in vivo evidence of neuroprotective and long-term effects that contribute to neurotrophic support and increased neuroplasticity. Presumably, the described effects of ACD856 may improve cognition, increase resilience, and promote neurorestorative processes, thereby leading to a healthier brain in patients with AD.

Tr1 cell-mediated protection against autoimmune disease by intranasal administration of a fusion protein targeting cDC1 cells.

Curative therapies against autoimmune diseases are lacking. Indeed, most of the currently available treatments are only targeting symptoms. We have developed a novel strategy for a therapeutic vaccine against autoimmune diseases based on intranasal administration of a fusion protein tolerogen, which consists of a mutant, enzymatically inactive, cholera toxin A1 (CTA1)-subunit genetically fused to disease-relevant high-affinity peptides and a dimer of D-fragments from protein A (DD). The CTA1 R7K mutant - myelin oligodendrocyte glycoprotein (MOG), or proteolipid protein (PLP) - DD (CTA1R7K-MOG/PLP-DD) fusion proteins effectively reduced clinical symptoms in the experimental autoimmune encephalitis model of multiple sclerosis. The treatment induced Tr1 cells, in the draining lymph node, which produced interleukin (IL)-10 and suppressed effector clusters of differentiation 4+ T-cell responses. This effect was dependent on IL-27 signaling because treatment was ineffective in bone marrow chimeras lacking IL-27Ra within their hematopoietic compartment. Single-cell RNA sequencing of dendritic cells in draining lymph nodes demonstrated distinct gene transcriptional changes of classic dendritic cells 1, including enhanced lipid metabolic pathways, induced by the tolerogenic fusion protein. Thus, our results with the tolerogenic fusion protein demonstrate the possibility to vaccinate and protect against disease progression by reinstating tolerance in multiple sclerosis and other autoimmune diseases.

Failure of early non-invasive ventilation in preterm infants with respiratory distress syndrome in current care practice in Spanish level-III neonatal intensive care units - a prospective observational study.

Introduction: Despite advances in respiratory distress syndrome (RDS) management over the past decade, non-invasive ventilation (NIV) failure is frequent and associated with adverse outcomes. There are insufficient data on the failure of different NIV strategies currently used in clinical practice in preterm infants. Methods: This was a prospective, multicenter, observational study of very preterm infants [gestational age (GA) <32 weeks] admitted to the neonatal intensive care unit for RDS that required NIV from the first 30 min after birth. The primary outcome was the incidence of NIV failure, defined as the need for mechanical ventilation for <72 h of life. Secondary outcomes were risk factors associated with NIV failure and complication rates. Results: The study included 173 preterm infants with a median GA of 28 (IQR 27-30) weeks and a median birth weight of 1,100 (IQR 800-1,333) g. The incidence of NIV failure was 15.6%. In the multivariate analysis, lower GA (OR, 0.728; 95% CI, 0.576-0.920) independently increased the risk of NIV failure. Compared to NIV success, NIV failure was associated with higher rates of unfavorable outcomes, including pneumothorax, intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, and a combined outcome of moderate-to-severe bronchopulmonary dysplasia or death. Conclusion: NIV failure occurred in 15.6% of the preterm neonates and was associated with adverse outcomes. The use of LISA and newer NIV modalities most likely accounts for the reduced failure rate. Gestational age remains the best predictor of NIV failure and is more reliable than the fraction of inspired oxygen during the first hour of life.

Identification of ACE I-Inhibitory Peptides Released by the Hydrolysis of Tub Gurnard (Chelidonichthys lucerna) Skin Proteins and the Impact of Their In Silico Gastrointestinal Digestion.

Tub gurnard is a highly abundant fishery species caught as a discard in the Mediterranean Sea. This work proposes its valorisation through the release of potential antihypertensive peptides and glycosaminoglycans (GAGs) through the controlled hydrolysis of tub gurnard skin proteins. Four proteases (Esperase, Alcalase, Trypsin and Pronase E) were used to obtain potent angiotensin converting enzyme I (ACE)-inhibitory hydrolysates. Peptides and GAGs were separated and evaluated for their antihypertensive potential by fluorometry. The peptide-rich fractions derived from the Esperase and Alcalase hydrolysates showed very low IC50 values (47 and 68 µg/mL, respectively). Only the GAGs from the Trypsin and Esperase hydrolysates were relevant ACE inhibitors (63 and 52% at 1 mg/mL, respectively). The peptide composition of the most potent ACE-inhibitory fractions derived from the Esperase and Alcalase hydrolysates (IC50 values of 33 and 29 µg/mL, respectively) was analysed by RP-LC-ESI-MS/MS. The analysis suggests that the ACE-inhibitory activity is related to the peptide hydrophobicity, as well as to the presence of specific residues at any of the last four C-terminal positions. The in silico gastrointestinal digestion of these fractions yielded small peptides with antihypertensive potential.