Prognostic nutritional index as a predictor of surgical complications in women with gynecological cancer.

OBJECTIVE: To analyze the association between the prognostic nutritional index and surgical morbidity in women with gynecologic cancers. METHODS: This is a retrospective cohort study of women with ovarian, endometrial, or cervical cancer who underwent surgery between January 2013 and December 2020 at a cancer center. Demographic and clinical data were extracted from electronic medical records. The prognostic nutritional index was calculated during the immediate pre-operative period. Binomial logistic regression was conducted to identify the association of the prognostic nutritional index with the outcome of surgical complications after Clavien-Dindo classification, adjusting for confounding variables. RESULTS: A total of 1000 women were included: 114 (11.4%) were diagnosed with cervical cancer, 551 (55.1%) with ovarian cancer, and 335 (33.5%) with endometrial cancer. Patients with a prognostic nutritional index >40 had a decreased possibility of surgical complications (OR=0.39, 95% CI 0.29 to 0.52); basal blood hemoglobin, volume of surgical bleeding, operative time, and length of hospital stay were also explanatory factors. The prognostic nutritional index has a significant effect on patients with endometrial and cervical cancer, but conversely is not significant in patients with ovarian cancer. CONCLUSION: The prognostic nutritional index is associated with surgical morbidity in endometrial and cervical cancers and thus can be a useful tool for predicting morbidity and guide pre-operative interventions in patients with gynecological cancers.

Practical Guidelines by the Andalusian Group for Nutrition Reflection and Investigation (GARIN) on Nutritional Management of Patients with Chronic Obstructive Pulmonary Disease: A Review.

Malnutrition is common in chronic obstructive pulmonary disease (COPD) patients and is associated with worse lung function and greater severity. This review by the Andalusian Group for Nutrition Reflection and Investigation (GARIN) addresses the nutritional management of adult COPD patients, focusing on Morphofunctional Nutritional Assessment and intervention in clinical practice. A systematic literature search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, followed by critical appraisal based on Scottish Intercollegiate Guidelines Network (SIGN) guidelines. Recommendations were graded according to the European Society for Clinical Nutrition and Metabolism (ESPEN) system. The results were discussed among GARIN members, with consensus determined using a Likert scale. A total of 24 recommendations were made: 2(A), 6(B), 2(O), and 14(GPP). Consensus exceeded 90% for 17 recommendations and was 75-90% for 7. The care of COPD patients is approached from a nutritional perspective, emphasizing nutritional screening, morphofunctional assessment, and food intake in early disease stages. Nutritional interventions include dietary advice, recommendations on food group intake, and the impact of specialized nutritional treatment, particularly oral nutritional supplements. Other critical aspects, such as physical activity and quality of life, are also analyzed. These recommendations provide practical guidance for managing COPD patients nutritionally in clinical practice.

Clinical and genomic diversity of Treponema pallidum subspecies pallidum to inform vaccine research: an international, molecular epidemiology study.

BACKGROUND: The increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We aimed to explore Treponema pallidum subspecies pallidum (TPA) molecular epidemiology essential for vaccine research by analysing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. METHODS: In this multicentre, cross-sectional, molecular epidemiology study, we enrolled patients with primary, secondary, or early latent syphilis from clinics in China, Colombia, Malawi, and the USA between Nov 28, 2019, and May 27, 2022. Participants aged 18 years or older with laboratory confirmation of syphilis by direct detection methods or serological testing, or both, were included. Patients were excluded from enrolment if they were unwilling or unable to give informed consent, did not understand the study purpose or nature of their participation, or received antibiotics active against syphilis in the past 30 days. TPA detection and WGS were conducted on lesion swabs, skin biopsies, skin scrapings, whole blood, or rabbit-passaged isolates. We compared our WGS data to publicly available genomes and analysed TPA populations to identify mutations associated with lineage and geography. FINDINGS: We screened 2802 patients and enrolled 233 participants, of whom 77 (33%) had primary syphilis, 154 (66%) had secondary syphilis, and two (1%) had early latent syphilis. The median age of participants was 28 years (IQR 22-35); 154 (66%) participants were cisgender men, 77 (33%) were cisgender women, and two (1%) were transgender women. Of the cisgender men, 66 (43%) identified as gay, bisexual, or other sexuality. Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants showed a predominance of SS14-lineage strains with geographical clustering. Phylogenomic analyses confirmed that Nichols-lineage strains were more genetically diverse than SS14-lineage strains and clustered into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models showed population-specific substitutions, some in outer membrane proteins (OMPs) of interest. INTERPRETATION: Our study substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains is vital for vaccine development and understanding syphilis pathogenesis on a population level. FUNDING: US National Institutes of Health National Institute for Allergy and Infectious Disease, the Bill & Melinda Gates Foundation, Connecticut Children's, and the Czech Republic National Institute of Virology and Bacteriology.

A Cross-Sectional Validation of Horos and CoreSlicer Software Programs for Body Composition Analysis in Abdominal Computed Tomography Scans in Colorectal Cancer Patients.

BACKGROUND: Body composition assessment using computed tomography (CT) scans may be hampered by software costs. To facilitate its implementation in resource-limited settings, two open-source segmentation programs (Horos and CoreSlicer) were transversally validated in colorectal cancer patients. METHODS: Contrast-enhanced abdominal CT scans were analyzed following the Alberta protocol. The Cross-Sectional Area (CSA) and intensities of skeletal muscle tissue (MT), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intramuscular adipose tissue (IMAT) were measured. The Skeletal Muscle Index (SMI) was calculated. Cutoff points were applied to the SMI, MT intensity, and VAT CSA to define muscle atrophy, myosteatosis, and abdominal obesity. The inter-software agreement was evaluated using different statistical tools. RESULTS: A total of 68 participants were measured. The MT CSA and SMI displayed no differences. The MT CSA agreement was excellent, and both programs provided equal muscle atrophy prevalences. CoreSlicer underestimated the MT intensity, with a non-significant myosteatosis prevalence increase (+5.88% and +8.82%) using two different operative definitions. CoreSlicer overestimated the CSA and intensity in both VAT and SAT, with a non-significant increase (+2.94%) in the abdominal obesity prevalence. CONCLUSIONS: Both software programs were feasible tools in the study group. The MT CSA showed great inter-software agreement and no muscle atrophy misdiagnosis. Segmentation differences in the MT intensity and VAT CSA caused limited diagnostic misclassification in the study sample.

Importance of local and systemic factors in preventing implant displacement in the mandibular body: a scoping review of existing literature.

BACKGROUND: The aim of this research was to analyse the current literature on displaced dental implants in the mandibular body, including local and systemic variables related to their cause, and to identify the most frequent location. METHODS: The study conducted a search of three databases (Pubmed, Scopus, and Web of Science) using specific index terms such as 'dental implant', 'displacement', 'dislocation', 'displaced', and 'mandible'. The analysis focused on the direction of displacement and the characteristics of the bone tissue (bone quality, density, and quantity) in cases where dental implants were displaced. RESULTS: A total of 371 articles were obtained. Thirteen of these articles were selected and read in full. To define bone quality, the Lekholm and Zarb classification, modified by Rosas et al., was used. The type II-B bone, which is characterized by thick cortical bone surrounding cancellous bone with extremely wide medullary spaces, presented the largest number of complications. Twenty-two cases were found in which the displacement direction was horizontal. Of these, four were displaced vestibularly, fourteen lingually, and four remained in the center. Additionally, 24 cases presented vertical displacement, with 12 displaced towards the inferior border of the mandible, 9 towards the middle or adjacent to the inferior dental nerve canal, and 3 above the inferior dental nerve canal. CONCLUSION: The accidental displacement of implants within the mandibular body is associated with various risk factors, including the characteristics of the bony trabeculum and the size of the medullary spaces. It is reasonable to suggest that only an adequate pre-surgical diagnostic evaluation, with the help of high-resolution tomographic images that allow a previous evaluation of these structures, will help to have better control over the other factors, thus minimizing the risk of displacement.

Antifungal Activity of Morinda citrifolia Methanolic Extract against Candida albicans: An In Vitro Study.

Aim: Natural medicine used as an alternative and/or complementary treatment to counteract diseases is of great importance in public health. Therefore, the purpose of the present study was to assess the in vitro antifungal activity of Morinda citrifolia methanolic extract of peel, pulp, and seed against Candida albicans. Materials and Methods: The present study was experimental in vitro and cross-sectional. Eight replicates were prepared in Sabouraud dextrose agar with five wells each, where 0.12% chlorhexidine, distilled water, and methanolic extract of seed, peel, and pulp of Morinda citrifolia fruit were placed at concentrations of 10,690, 8,270, and 6,430 mg/mL, respectively, to evaluate sensitivity according to Duraffourd's scale. In addition, the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined by dilution and agar seeding method. Statistical analysis was performed by analysis of variance (ANOVA) and Tukey's post hoc test, considering a significance level of P < 0.05. Results: The inhibition halos of Morinda citrifolia methanolic extract of seed, peel, and pulp against Candida albicans measured on average 15.94, 11.94, and 11.56 mm, respectively. The MIC of seed, peel, and pulp extract were 1366.25, 2067.5, and 1607.5 mg/mL respectively, whereas the MFC for seed, peel, and pulp extract were 2672.50, 2067.5, and 3215 mg/mL, respectively. Moreover, seed extract presented significantly higher antifungal activity than peel and pulp (P < 0.001). Conclusions: Morinda citrifolia methanolic extract of peel, pulp, and seed showed fungistatic and fungicidal effect against Candida albicans, being this very sensitive to seed extract with a MIC of 1366.25 mg/mL and a MFC of 2672.5 mg/mL, which allows recommending the development of effective pharmacological formulations for the control of candidiasis.

Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia.

BACKGROUND: Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations. The aim of this study was to describe the clinical, demographic, and molecular features of early syphilis cases in Cali, Colombia. METHODS AND FINDINGS: We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by polA quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest polA copy numbers (67 copies/µl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 polA copies/µl with PR of 62%. WB polA positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of TPA from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (i.e., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein's predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American TPA isolates. CONCLUSIONS: This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent TPA strains can inform vaccine development.

Ultrasound Cut-Off Values for Rectus Femoris for Detecting Sarcopenia in Patients with Nutritional Risk.

BACKGROUND: A nationwide, prospective, multicenter, cohort study (the Disease-Related caloric-protein malnutrition EChOgraphy (DRECO) study) was designed to assess the usefulness of ultrasound of the rectus femoris for detecting sarcopenia in hospitalized patients at risk of malnutrition and to define cut-off values of ultrasound measures. METHODS: Patients at risk of malnutrition according to the Malnutrition Universal Screening Tool (MUST) underwent handgrip dynamometry, bioelectrical impedance analysis (BIA), a Timed Up and Go (TUG) test, and rectus femoris ultrasound studies. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were used to define categories of sarcopenia (at risk, probable, confirmed, severe). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the optimal diagnostic sensitivity, specificity, and predictive values of cut-off points of the ultrasound measures for the detection of risk of sarcopenia and probable, confirmed, and severe sarcopenia. RESULTS: A total of 1000 subjects were included and 991 of them (58.9% men, mean age 58.5 years) were evaluated. Risk of sarcopenia was detected in 9.6% patients, probable sarcopenia in 14%, confirmed sarcopenia in 9.7%, and severe sarcopenia in 3.9%, with significant differences in the distribution of groups between men and women (p < 0.0001). The cross-sectional area (CSA) of the rectus femoris showed a significantly positive correlation with body cell mass of BIA and handgrip strength, and a significant negative correlation with TUG. Cut-off values were similar within each category of sarcopenia, ranging between 2.40 cm2 and 3.66 cm2 for CSA, 32.57 mm and 40.21 mm for the X-axis, and 7.85 mm and 10.4 mm for the Y-axis. In general, these cut-off values showed high sensitivities, particularly for the categories of confirmed and severe sarcopenia, with male patients also showing better sensitivities than women. CONCLUSIONS: Sarcopenia in hospitalized patients at risk of malnutrition was high. Cut-off values for the better sensitivities and specificities of ultrasound measures of the rectus femoris are established. The use of ultrasound of the rectus femoris could be used for the prediction of sarcopenia and be useful to integrate nutritional study into real clinical practice.

A Cross-Sectional Validation Study of Camry EH101 versus JAMAR Plus Handheld Dynamometers in Colorectal Cancer Patients and Their Correlations with Bioelectrical Impedance and Nutritional Status.

BACKGROUND: Reduced muscle strength (dynapenia) and mass (atrophy) are prognostic factors in oncology. Measuring maximal handgrip strength with dynamometers is feasible but limited by the cost of the reference device (JAMAR). METHODS: A cross-sectional study was conducted on colorectal cancer outpatients treated with chemotherapy or under active surveillance in our center from September 2022 to July 2023. Accuracy, reliability, and concordance were compared for two handheld dynamometers: the JAMAR Plus (the gold-standard device) and the Camry EH101 (a low-cost index device). A simultaneous nutritional diagnosis with GLIM criteria and bioelectrical impedance analysis (BIA) was carried out. RESULTS: A total of 134 participants were included. The median of maximal strength for the JAMAR Plus had a non-significant difference of 1.4 kg from the Camry EH101. The accuracy and reliability of the devices were high. Bland-Altman analysis showed a 0.8 kg bias and -4.1 to 5.6 kg limits of agreement (LoA); a 0.1 kg bias and -5.3 to 5.4 kg LoA in men; a 1.5 kg bias and -2.2 to 5.3 kg LoA in women. In total, 29.85% of the participants were malnourished. Prevalence of dynapenia increased from 3.67% with the JAMAR Plus to 5.14% with the Camry EH101. Both devices had a moderate and significant correlation with BIA-estimated muscle mass. CONCLUSIONS: The Camry EH101 was a cost-effective alternative to JAMAR Plus in our sample.

A Descriptive Study of Quality of Life Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND: Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life (QOL). Transoral robotic surgery (TORS) has an established role in the management of early OPSCC but adjuvant treatment is often indicated postoperatively due to the high incidence of nodal metastasis associated with advanced human papillomavirus (HPV)-related OPSCC. To overcome the need for adjuvant radiation therapy (RT), neoadjuvant chemotherapy followed by TORS and neck dissection (ND) is proposed. This study aimed to assess if QOL in HPV-associated OPSCC receiving neoadjuvant chemotherapy followed by TORS and ND returns to baseline within 12 months of completing treatment. METHODS: A 12 month longitudinal study was carried out at McGill University Health Centre in Montreal, Canada, among a convenience sample of patients with American Joint Committee on Cancer Seventh Edition stage III and IVa HPV-related OPSCC who were treated with neoadjuvant chemotherapy followed by TORS and ND. QOL data were obtained pretreatment and at 1, 3, 6, and 12 months following treatment completion using the European Organisation for Research and Treatment of Cancer Core and Head and Neck extension modules. Paired t tests and mixed models for repeated measures analysis were used to assess changes in QOL from baseline to 12 months postoperatively and over time, respectively. RESULTS: Nineteen of 23 patients (median age 58 years) who received the study treatment fulfilled the eligibility criteria. OPSCC subsites were palatine tonsil (n = 12) and base of tongue (n = 7). All 19 patients were treated per protocol and none required adjuvant RT as per pathology review and protocol requirements at a postoperative multidisciplinary team tumor board discussion. No significant differences were found when comparing 12 month QOL follow-up scores to pretreatment scores in measures that would likely be affected by RT [eg, swallowing (P = .7), social eating (P = .8), xerostomia (P = .9)]. CONCLUSION: In HPV-related OPSCC, neoadjuvant chemotherapy followed by TORS and ND as definitive treatment is associated with excellent QOL outcomes. Postoperative QOL scores returned to baseline by 3 months and were maintained for all measures, indicating a return to normal function.

Consenso sobre criterios y conjunto mínimo de datos para la derivación de pacientes candidatos a teleconsulta de nutrición enteral domiciliaria: proyecto TElENUT / Consensus on criteria and minimum data set for the referral of candidate patients for home enteral nutrition teleconsultation: TELENUT project

Introducción: la teleconsulta es una herramienta asistencial útil en el manejo multidisciplinar de pacientes con indicación de nutrición enteral domiciliaria (NED). El empleo de diferentes herramientas de teleconsulta de NED, como ocurre en el Sistema Andaluz de Salud (SAS), conlleva heterogeneidad en los procesos de derivación entre los servicios de Atención Primaria (AP) y hospitalaria en una misma región. Objetivos: consensuar perfiles de pacientes y conjunto de datos mínimos necesarios para garantizar una derivación adecuada a la teleconsulta de NED, independientemente de la herramienta existente. Estos aspectos consensuados en Andalucía pueden servir de referencia en otras regiones. Métodos: se siguieron tres pasos consecutivos: a) revisión no sistemática de la literatura indexada sobre la teleconsulta en nutrición clínica en España; b) encuesta para conocer la implementación y las necesidades no satisfechas de las herramientas de teleconsulta en los hospitales públicos andaluces; y c) reuniones de trabajo y consenso de 14 profesionales sanitarios de AP (n = 4) y endocrinología y nutrición clínica hospitalaria (n = 10). Resultados: se consensuaron tres formularios de derivación en los que se definieron tres perfiles de pacientes, con el correspondiente conjunto mínimo de datos necesario para solicitar la teleconsulta de NED. El equipo de AP debe proporcionar este conjunto mínimo de datos al especialista en nutrición clínica a través de una herramienta de teleconsulta, implementada en el SAS. Conclusiones: tres formularios consensuados entre profesionales sanitarios involucrados en el proceso de derivación sirven para estandarizar la solicitud de teleconsulta de NED entre equipos asistenciales en función de perfiles de pacientes.(AU)

Introduction: teleconsultation is a useful healthcare tool in the multidisciplinary management of patients with indications of home enteral nutrition (HEN). The use of different teleconsultation platforms, as it happens in the Andalusian Health System (SAS), results in heterogeneous referral processes between Primary Care and hospital services in the same region. Objectives: to establish a consensus on patient profiles and the minimum data set necessary to guarantee an adequate referral to NED teleconsultation regardless of the existing platform. These agreed aspects in Andalusia can serve as a reference in other regions. Methods: three consecutive steps were followed: a) non-systematic review of the indexed literature on teleconsultation in clinical nutrition in Spain; b) survey to know the implementation and unmet needs of teleconsultation platforms in Andalusian public hospitals; and c) working meetings and consensus of 14 health professionals of Primary Care (n = 4) and endocrinology and hospital clinical nutrition (n = 10). Results: three referral forms were agreed in which three patient profiles were defined, with the corresponding minimum set of data necessary to request NED teleconsultation. The Primary Care team should provide this set of data to the clinical nutrition specialist via a teleconsultation platform, implemented in the SAS. Conclusions: three agreed forms between healthcare professionals involved in the referral process serve to standardize the request for teleconsultation of NED between healthcare teams based on patient profiles.(AU)

Percutaneous Gastrostomies: Associated Complications in PUSH vs. PULL Techniques over 12 Years in a Referral Centre.

Objectives: To compare complications associated with percutaneous gastrostomies performed using PUSH and PULL techniques, whether endoscopic (PEG) or radiological (PRG), in a tertiary-level hospital. Methods: This was a prospective observational study. Adult patients who underwent percutaneous PULL or PUSH gastrostomy using PEG or PRG techniques at the Virgen del Rocio University Hospital and subsequently followed up in the Nutrition Unit between 2009-2020 were included. X2 tests or Fisher's test were used for the comparison of proportions when necessary. Univariate analysis was conducted to study risk factors for PRG-associated complications. Results: n = 423 (PULL = 181; PUSH = 242). The PULL technique was associated with a higher percentage of total complications (37.6% vs. 23.8%; p = 0.005), exudate (18.2% vs. 11.2%; p = 0.039), and irritation (3.3% vs. 0%; p = 0.006). In the total sample, there were 5 (1.1%) cases of peritonitis, 3 (0.7%) gastrocolic fistulas, and 1 (0.2%) death due to complications associated with gastrostomy. Gender, age, and different indications were not risk factors for a higher number of complications. The most common indications were neurological diseases (35.9%), head and neck cancer (29%), and amyotrophic lateral sclerosis (17.2%). Conclusions: The PULL technique was associated with more total complications than the PUSH technique, but both were shown to be safe techniques, as the majority of complications were minor.

Recombinant CD5 and CD6 Ectodomains Induce Antiparasitic and Immunomodulatory Effects in Secondary Cystic Echinococcosis.

Scavenger receptors participate in a wide range of biological functions after binding to multiple non-self or altered self-ligands. Among them, CD5 and CD6 are lymphocyte scavenger receptors known to interact with different microbial-associated molecular patterns, and the administration of the recombinant soluble ectodomains of human CD5 (rshCD5) and/or CD6 (rshCD6) has shown therapeutic/prophylactic potential in experimental models of fungal, bacterial and echinococcal infections. The latter is a zoonosis caused by the larval stage of the cestode parasite Echinococcus granulosus sensu lato, which in humans can induce secondary cystic echinococcosis (CE) after the spillage of protoscoleces contained within fertile cysts, either spontaneously or during surgical removal of primary hydatid cysts. Herein, we have analysed the mechanisms behind the significant protection observed in the mouse model of secondary CE following prophylactic administration of rshCD5 or rshCD6. Our results show that both molecules exhibit intrinsic antiparasitic activities in vitro, as well as immunomodulatory functions during early secondary CE, mainly through Th1/Th17 cytokine bias and promotion of peritoneal polyreactive antibodies. These data support the relevance of the parasite components bound by rshCD5 and rshCD6, as well as the potential of their prophylactic administration as a useful strategy to reduce secondary CE in patients.

Physiologically based pharmacokinetics modeling and transporter proteomics to predict systemic and local liver and muscle disposition of statins.

Statins are used to reduce liver cholesterol levels but also carry a dose-related risk of skeletal muscle toxicity. Concentrations of statins in plasma are often used to assess efficacy and safety, but because statins are substrates of membrane transporters that are present in diverse tissues, local differences in intracellular tissue concentrations cannot be ruled out. Thus, plasma concentration may not be an adequate indicator of efficacy and toxicity. To bridge this gap, we used physiologically based pharmacokinetic (PBPK) modeling to predict intracellular concentrations of statins. Quantitative data on transporter clearance were scaled from in vitro to in vivo conditions by integrating targeted proteomics and transporter kinetics data. The developed PBPK models, informed by proteomics, suggested that organic anion-transporting polypeptide 2B1 (OATP2B1) and multidrug resistance-associated protein 1 (MRP1) play a pivotal role in the distribution of statins in muscle. Using these PBPK models, we were able to predict the impact of alterations in transporter function due to genotype or drug-drug interactions on statin systemic concentrations and exposure in liver and muscle. These results underscore the potential of proteomics-guided PBPK modeling to scale transporter clearance from in vitro data to real-world implications. It is important to evaluate the role of drug transporters when predicting tissue exposure associated with on- and off-target effects.

Effects of Blood flow Restriction and Load on Mean Propulsive Velocity and Subjective Perceived Exertion During Squat and Bench Press Exercises.

BACKGROUND: The aim of this study was to determine the influence of different percentages of blood flow restriction (BFR) and loads on mean propulsive velocity (MPV) and subjective perceived exertion during squat (SQ) and bench press (BP) exercises. HYPOTHESIS: Higher percentages of BFR will positively affect dependent variables, increasing MPV and reducing perceived exertion. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: Eight healthy young male athletes took part. Two sets of 6 repetitions at 70% 1-repetition maximum (1RM), 2 sets of 4 repetitions at 80% 1RM, and 2 sets of 2 repetitions at 90% 1RM were performed randomly; 5-minute recoveries were applied in all sets. The varying arterial occlusion pressure (AOP) applied randomly was 0% (Control [CON]), 80%, and 100%. RESULTS: No statistically significant differences in MPV were found during the BP exercise at any percentage of BFR at any percentage 1RM. During the SQ exercise, MPV results showed statistically significant increases of 5.46% (P = 0.04; ηp2 = 0.31) between CON and 100% AOP at 90% 1RM. The perceived exertion results for the BP exercise showed statistically significant reductions of -8.66% (P < 0.01; ηp2 = 0.06) between CON and 100% AOP at 90% 1RM. During the SQ exercise, the perceived exertion results showed significant reductions of -10.04% (P = 0.04; ηp2 = 0.40) between CON and 100% AOP at 80% 1RM; -5.47% (P = 0.02; ηp2 = 0.48) between CON and 80% AOP at 90% 1RM; and -11.83% (P < 0.01; ηp2 = 0.66) between CON and 100% AOP at 90% 1RM. CONCLUSION: BFR percentages ~100% AOP at 90% 1RM improved acutely MPV (only in SQ exercises) and reduced acutely perceived exertion (in both exercises). These findings are important to consider when prescribing resistance training for healthy male athletes.

Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure.

Optimization of the highly potent and selective, yet metabolically unstable and poorly soluble hRXFP1 agonist AZ7976 led to the identification of the clinical candidate, AZD5462. Assessment of RXFP1-dependent cell signaling demonstrated that AZD5462 activates a highly similar panel of downstream pathways as relaxin H2 but does not modulate relaxin H2-mediated cAMP second messenger responsiveness. The therapeutic potential of AZD5462 was assessed in a translatable cynomolgus monkey heart failure model. Following 8 weeks of treatment with AZD5462, robust improvements in functional cardiac parameters including LVEF were observed at weeks 9, 13, and 17 without changes in heart rate or mean arterial blood pressure. AZD5462 was well tolerated in both rat and cynomolgus monkey and has successfully completed phase I studies in healthy volunteers. In summary, AZD5462 is a small molecule pharmacological mimetic of relaxin H2 signaling at RXFP1 and holds promise as a potential therapeutic approach to treat heart failure patients.

Tasa de resangrado vítreo posterior a vitrectomía o facovitrectomía en pacientes con retinopatía diabética proliferativa: estudio retrospectivo / Vitreous rebleeding rate after vitrectomy or phacovitrectomy in patients with proliferative diabetic retinopathy: A retrospective study

Antecedentes: La complicación más común tras la vitrectomía en pacientes es el resangrado en cavidad vítrea. Es importante detectar los distintos factores que pueden incrementar la tasa de resangrado vítreo en estos pacientes. Objetivo: Realizar una revisión retrospectiva de la tasa de resangrado de cavidad vítrea posterior a vitrectomía o facovitrectomía. Método: Estudio retrospectivo, descriptivo y comparativo de pacientes con diagnóstico de retinopatía diabética proliferativa con procedimiento de facovitrectomía o vitrectomía. Se obtuvieron datos de antecedentes personales patológicos, tipo de intervención quirúrgica y grado del cirujano que realizó el procedimiento. Resultados: Se revisaron 1.227 expedientes de pacientes diabéticos sometidos a vitrectomía o facovitrectomía. El 65% presentaron hipertensión arterial sistémica. La tasa de filtración glomerular promedio fue del 63,50 (±32,36) ml/min/1,73m2 y la de hemoglobina glucosilada (HbA1c) del 8% (4,6 al 15%). En la comparación de variables se obtuvo una diferencia significativa de la tasa de resangrado vítreo comparando la facovitrectomía con la vitrectomía (p=0,003), y al relacionar la vitrectomía con el resangrado, se obtuvo una razón de momios de 1,44. Conclusión: Los resultados obtenidos muestran una menor tasa de resangrado en los pacientes con retinopatía diabética proliferativa sometidos a facovitrectomía.(AU)

Background: The most common complication after vitrectomy is the rebleeding in vitreous cavity. It is important to detect the different factors that can increase the vitreous rebleeding rate in these patients. Objective: To carry out a retrospective review of the rate of vitreous rebleeding after vitrectomy or phacovitrectomy. Method: Retrospective, descriptive and comparative study of patients with a diagnosis of proliferative diabetic retinopathy with phacovitrectomy or vitrectomy procedure. Personal background data, type of surgical intervention and grade of the surgeon who carried out the procedure were obtained. Results: One thousand two hundred twenty-seven files of diabetic patients with vitrectomy or phacovitrectomy were reviewed. Sixty-five percent presented systemic arterial hypertension. The average glomerular filtration rate was 63.50 (±32.36)ml/min/1.73m2 and glycosylated hemoglobin (HBA1C) of 8% (4.6-15%). In the comparison of variables, a significant difference in the rate of vitreous rebleeding was obtained comparing phacovitrectomy with vitrectomy (P=.003), in the relationship between vitrectomy with vitreous rebleeding, an odds ratio of 1.44 was obtained. Conclusion: The results obtained show a lower rate of rebleeding in patients undergoing phacovitrectomy in patients with proliferative diabetic retinopathy.(AU)

Ultrasound Muscle Evaluation for Predicting the Prognosis of Patients with Head and Neck Cancer: A Large-Scale and Multicenter Prospective Study.

Head and neck cancer (HNC) is a prevalent and aggressive form of cancer with high mortality rates and significant implications for nutritional status. Accurate assessment of malnutrition in patients with HNC is crucial for optimizing treatment outcomes and improving survival rates. This study aimed to evaluate the use of ultrasound techniques for predicting nutritional status, malnutrition, and cancer outcomes in patients with HNC. A total of 494 patients with HNC were included in this cross-sectional observational study. Various tools and body composition measurements, including muscle mass and adipose tissue ultrasound evaluations, were implemented. Using regression models, we mainly found that high levels of RF-CSA (rectus femoris cross-sectional area) were associated with a decreased risk of malnutrition (as defined with GLIM criteria (OR = 0.81, 95% CI: 0.68-0.98); as defined with PG-SGA (OR = 0.78, 95% CI: 0.62-0.98)) and sarcopenia (OR = 0.64, 95% CI: 0.49-0.82) after being adjusted for age, sex, and BMI. To predict the importance of muscle mass ultrasound variables on the risk of mortality, a nomogram, a random forest, and decision tree models were conducted. RF-CSA was the most important variable under the random forest model. The obtained C-index for the nomogram was 0.704, and the Brier score was 16.8. With an RF-CSA < 2.7 (AUC of 0.653 (0.59-0.77)) as a split, the decision tree model classified up to 68% of patients as possessing a high probability of survival. According to the cut-off value of 2.7 cm2, patients with a low RF-CSA value lower than 2.7 cm2 had worse survival rates (p < 0.001). The findings of this study highlight the importance of implementing ultrasound tools, for accurate diagnoses and monitoring of malnutrition in patients with HNC. Adipose tissue ultrasound measurements were only weakly associated with malnutrition and not with sarcopenia, indicating that muscle mass is a more important indicator of overall health and nutritional status. These results have the potential to improve survival rates and quality of life by enabling early intervention and personalized nutritional management.

Two Adverse Early Life Events Induce Differential Changes in Brain CRH and Serotonin Systems in Rats along with Hyperphagia and Depression.

BACKGROUND: Different types of stress inflicted in early stages of life elevate the risk, among adult animals and humans, to develop disturbed emotional-associated behaviors, such as hyperphagia or depression. Early-life stressed (ELS) adults present hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis, which is a risk factor associated with mood disorders. However, the prevalence of hyperphagia (17%) and depression (50%) is variable among adults that experienced ELS, suggesting that the nature, intensity, and chronicity of the stress determines the specific behavioral alteration that those individuals develop. METHODS: We analyzed corticosterone serum levels, Crh, GR, Crhr1 genes expression in the hypothalamic paraventricular nucleus, amygdala, and hippocampus due to their regulatory role on HPA axis in adult rats that experienced maternal separation (MS) or limited nesting material (LNM) stress; as well as the serotonergic system activity in the same regions given its association with the corticotropin-releasing hormone (CRH) pathway functioning and with the hyperphagia and depression development. RESULTS: Alterations in dams' maternal care provoked an unresponsive or hyper-responsive HPA axis function to an acute stress in MS and LNM adults, respectively. The differential changes in amygdala and hippocampal CRH system seemed compensating alterations to the hypothalamic desensitized glucocorticoids receptor (GR) in MS or hypersensitive in LNM. However, both adult animals developed hyperphagia and depression-like behavior when subjected to the forced-swimming test, which helps to understand that both hypo and hypercortisolemic patients present those disorders. CONCLUSION: Different ELS types induce neuroendocrine, brain CRH and 5-hydroxytriptamine (5-HT) systems' alterations that may interact converging to develop similar maladaptive behaviors.

Concurrent Validity of the Ergotex Device for Measuring Low Back Posture.

Highlighting the crucial role of monitoring and quantifying lumbopelvic rhythm for spinal curvature, the Ergotex IMU, a portable, lightweight, cost-effective, and energy-efficient technology, has been specifically designed for the pelvic and lumbar area. This study investigates the concurrent validity of the Ergotex device in measuring sagittal pelvic tilt angle. We utilized an observational, repeated measures design with healthy adult males (mean age: 39.3 ± 7.6 y, body mass: 82.2 ± 13.0 kg, body height: 179 ± 8 cm), comparing Ergotex with a 3D optical tracking system. Participants performed pelvic tilt movements in anterior, neutral, and posterior conditions. Statistical analysis included paired samples t-tests, Bland-Altman plots, and regression analysis. The findings show minimal systematic error (0.08° overall) and high agreement between the Ergotex and optical tracking, with most data points falling within limits of agreement of Bland-Altman plots (around ±2°). Significant differences were observed only in the anterior condition (0.35°, p < 0.05), with trivial effect sizes (ES = 0.08), indicating that these differences may not be clinically meaningful. The high Pearson's correlation coefficients across conditions underscore a robust linear relationship between devices (r > 0.9 for all conditions). Regression analysis showed a standard error of estimate (SEE) of 1.1° with small effect (standardized SEE < 0.26 for all conditions), meaning that the expected average deviation from the true value is around 1°. These findings validate the Ergotex as an effective, portable, and cost-efficient tool for assessing sagittal pelvic tilt, with practical implications in clinical and sports settings where traditional methods might be impractical or costly.