Prospective validation of the nutrition screening tool for childhood cancer (SCAN).

BACKGROUND & AIMS: Different nutritional screening tools have been proposed in childhood cancer, but none has shown convincing predictive capacity so far. The "nutrition screening tool for childhood cancer (SCAN)" has been specifically designed for this population and provides an easy-to-use, promising approach to identify patients at risk of malnutrition. We aim to: 1. Validate the SCAN tool prospectively in identifying malnourished patients or those who required nutritional support 2. Validate the SCAN tool prospectively in predicting toxicities or outcome. 3. Compare performance of a pediatric screening tool (STRONGKIDS) with SCAN. METHODS: Children in our center with a new diagnosis of cancer from August 2018 to May 2019 were offered to participate in the study. Measurements (SCAN questionnaire, weight, height, body-mass index (BMI), and mid upper-arm circumference (MUAC)) were taken at diagnosis and at regular intervals throughout therapy. The last measurement was taken 6 months after finishing the intensive treatment phase. SCAN score at diagnosis was validated prospectively against variables of interest. RESULTS: A total of 49 patients were recruited. When considering malnutrition during therapy the SCAN tool showed a sensitivity of 37.5% and negative predictive value (NPV) of 81%. Patients who required nutritional support were identified with a sensitivity of 50% and NPV of 62%. The SCAN tool was not able to predict increased toxicities, risk of relapse or decreased survival. The pediatric screening tool STRONGKIDS was unable to discriminate nutritional risk and labeled all 49 patients (100%) as medium or high-risk. Applying SCAN periodically during therapy increased sensitivity for identifying malnutrition to 87.5%. CONCLUSIONS: In our study, applying the SCAN tool at diagnosis showed low sensitivity in identifying patients who go on to develop malnutrition during therapy. However, patients labeled as "not at risk" were unlikely to need nutritional support in the form of nasogastric tube or total parenteral nutrition. Using SCAN throughout therapy could be helpful in building awareness for malnutrition and successfully discriminates between patients who need further support and those who don't.

Effectiveness of Therapeutic Exercise for Children Undergoing Treatment for Cancer: A Systematic Review: Therapeutic Exercise Children Cancer.

PURPOSE: To evaluate the effectiveness of therapeutic physical exercise (TPE) interventions on the physical functioning, psychosocial well-being, and quality of life (QoL) of children undergoing treatment for cancer. METHOD: Systematic review: databases were searched in April 2023. Selection criteria: children (<18 years old) undergoing treatment for cancer or a malignant neoplasm, randomized controlled trial design, utilization of TPE, and including physical and psychosocial outcomes. Internal validity was measured with Physiotherapy Evidence Database scale. RESULTS: Seven randomized controlled trials were included. Most studies showed that strength, fatigue, and QoL improved after the intervention. Cardiorespiratory capacity through 6-minute walk test and physical activity levels were better in the experimental groups. No changes were noted in other variables. CONCLUSIONS: This review supports the importance of a TPE program during cancer treatment, with the aim of maintaining physical capacities and counteracting physical inactivity.

Complications and adverse events in lymphadenectomy of the inguinal area: worldwide expert consensus.

BACKGROUND: Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes. The aim of this study was to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events in lymphadenectomy of the inguinal area (CALI) group. METHODS: A modified 3-round Delphi consensus approach surveyed a worldwide group of experts in inguinal lymph node dissection for melanoma, penile and vulval cancer. The group of experts included general surgeons, urologists and oncologists (gynaecological and surgical). The survey assessed expert agreement on inguinal lymph node dissection perioperative complications. Panel interrater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α. RESULTS: Forty-seven experienced consultants were enrolled: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons and 4 (8.5%) gynaecology oncologists. Based on their expertise, 31 (66%), 10 (21.3%) and 22 (46.8%) of the participants treat penile cancer, vulval cancer and melanoma using inguinal lymph node dissection respectively; 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into five macrocategories. Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer and penile cancer. CONCLUSION: The complications and adverse events in lymphadenectomy of the inguinal area classification system has been developed as a tool to standardize the assessment and reporting of complications during inguinal lymph node dissection for the treatment of melanoma, vulval and penile cancer.

The Era of DAAs: Assessing the Patients' Characteristics, Clinical Impact, and Emergence of Comorbidities in HIV/HCV-Coinfected versus HIV-Infected Individuals.

Objective: To determine whether HIV-infected individuals versus individuals with HIV/HCV coinfection, in the era of interferon-free therapies, exhibit an increased incidence of comorbidities and non-AIDS-related events. Methods: A retrospective analysis was conducted by collecting data from clinical records of Spanish patients at a tertiary hospital involving HIV/HCV-coinfected and HIV-infected patients, all with effectively controlled HIV. Coinfected patients underwent HCV clearance using direct-acting antivirals (DAAs) and had no history of interferon treatment. The incidences of hypertension, diabetes mellitus, cardiovascular disease, kidney disease, liver disease, non-AIDS cancer, and death were compared between the groups. Multivariate adjustments for all factors potentially impacting outcomes were used to assess the risk of clinical event onset. Propensity score (PS) analyses were also conducted to support the multivariate model results. Results: Data were available from 229 HIV/HCV-coinfected patients and 229 HIV-infected patients. Both cohorts were comparable in terms of age, gender distribution, follow-up, and HIV-related characteristics. Multivariate models and PS showed that previous exposure to HCV was not associated with the onset of any clinical events studied. Significant differences between HIV/HCV-coinfected and HIV-infected were not found for survival according to the log-rank test (p = 0.402). Conclusions: Successful HCV elimination using DAAs improved the outlook regarding comorbidities and survival across HIV/HCV-coinfected cohorts. Early HCV detection and DAA therapy could enhance clinical results. These findings provide an optimistic perspective for those living with HIV/HCV coinfection and underscore the importance of continuing efforts toward early detection and DAA treatment initiation.

Structural basis of homodimerization of the JNK scaffold protein JIP2 and its heterodimerization with JIP1.

The scaffold proteins JIP1 and JIP2 intervene in the c-Jun N-terminal kinase (JNK) pathway to mediate signaling specificity by coordinating the simultaneous assembly of multiple kinases. Using NMR, we demonstrate that JIP1 and JIP2 heterodimerize via their SH3 domains with the affinity of heterodimerization being comparable to homodimerization. We present the high-resolution crystal structure of the JIP2-SH3 homodimer and the JIP1-JIP2-SH3 heterodimeric complex. The JIP2-SH3 structure reveals how charge differences in residues at its dimer interface lead to formation of compensatory hydrogen bonds and salt bridges, distinguishing it from JIP1-SH3. In the JIP1-JIP2-SH3 complex, structural features of each homodimer are employed to stabilize the heterodimer. Building on these insights, we identify key residues crucial for stabilizing the dimer of both JIP1 and JIP2. Through targeted mutations in cellulo, we demonstrate a functional role for the dimerization of the JIP1 and JIP2 scaffold proteins in activation of the JNK signaling pathway.

[Self-care education during Cardiac Rehabilitation programs for patients with Heart Failure with preserved Ejection Fraction: a Delphi Study]. / Educación en autocuidado durante programas de rehabilitación cardiaca para pacientes con insuficiencia cardiaca con fracción de eyección preservada: estudio Delphi.

OBJECTIVES: To develop a decalogue of self-care competencies to manage educational intervention during Cardiac Rehabilitation (CR) programs in Heart Failure with preserved Ejection Fraction (HFpEF) patients through multidisciplinary consensus. DESIGN: 3-round e-Delphi study using an initial questionnaire of 23 competencies based on the main recommendations of the CR and self-care guidelines. SITE: It was framed under the ethics of a randomised clinical trial developed at the Regional Hospital of Malaga. The survey was designed and disseminated as an online questionnaire. PARTICIPANTS: The expert panel comprised two patients with HFpEF and 13 healthcare professionals from Internal Medicine (n=3), Cardiology (n=2), Physiotherapy (n=3), Nursing (n=3) and Occupational Therapy (n=2). METHOD: The analysis of results included the content validity index, the percentage of agreement, and the concordance using Fleiss Kappa and Krippendorff's alpha. RESULTS: After the third round, 20 self-care competencies were identified, grouped into 12 domains, with sufficient consensus for their inclusion in the decalogue. CONCLUSIONS: The decalogue of self-care competencies generated from the multidisciplinary consensus guides education in patients with HFpEF, systematically addressing educational content tailored to patients for clinical practice in CR programs.

Gut microbiome in endometriosis: a cohort study on 1000 individuals.

BACKGROUND: Endometriosis, defined as the presence of endometrial-like tissue outside of the uterus, is one of the most prevalent gynecological disorders. Although different theories have been proposed, its pathogenesis is not clear. Novel studies indicate that the gut microbiome may be involved in the etiology of endometriosis; nevertheless, the connection between microbes, their dysbiosis, and the development of endometriosis is understudied. This case-control study analyzed the gut microbiome in women with and without endometriosis to identify microbial targets involved in the disease. METHODS: A subsample of 1000 women from the Estonian Microbiome cohort, including 136 women with endometriosis and 864 control women, was analyzed. Microbial composition was determined by shotgun metagenomics and microbial functional pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Partitioning Around Medoids (PAM) algorithm was performed to cluster the microbial profile of the Estonian population. The alpha- and beta-diversity and differential abundance analyses were performed to assess the gut microbiome (species and KEGG orthologies (KO)) in both groups. Metagenomic reads were mapped to estrobolome-related enzymes' sequences to study potential microbiome-estrogen metabolism axis alterations in endometriosis. RESULTS: Diversity analyses did not detect significant differences between women with and without endometriosis (alpha-diversity: all p-values > 0.05; beta-diversity: PERMANOVA, both R 2 < 0.0007, p-values > 0.05). No differential species or pathways were detected after multiple testing adjustment (all FDR p-values > 0.05). Sensitivity analysis excluding women at menopause (> 50 years) confirmed our results. Estrobolome-associated enzymes' sequence reads were not significantly different between groups (all FDR p-values > 0.05). CONCLUSIONS: Our findings do not provide enough evidence to support the existence of a gut microbiome-dependent mechanism directly implicated in the pathogenesis of endometriosis. To the best of our knowledge, this is the largest metagenome study on endometriosis conducted to date.

Confounding Factors in Targeted Degradation of Short-Lived Proteins.

Targeted protein degradation has recently emerged as a novel option in drug discovery. Natural protein half-life is expected to affect the efficacy of degrading agents, but to what extent it influences target protein degradation has not been systematically explored. Using simple mathematical modeling of protein degradation, we find that the natural half-life of a target protein has a dramatic effect on the level of protein degradation induced by a degrader agent which can pose significant hurdles to screening efforts. Moreover, we show that upon screening for degraders of short-lived proteins, agents that stall protein synthesis, such as GSPT1 degraders and generally cytotoxic compounds, deceptively appear as protein-degrading agents. This is exemplified by the disappearance of short-lived proteins such as MCL1 and MDM2 upon GSPT1 degradation and upon treatment with cytotoxic agents such as doxorubicin. These findings have implications for target selection as well as for the type of control experiments required to conclude that a novel agent works as a bona fide targeted protein degrader.

A Rare Case of Biloma after Ascending Cholangitis and Endoscopic Retrograde Cholangiopancreatography.

Introduction: Biloma is an uncommon form of liver abscess composed of bile usually associated with procedures of the biliary tree and gallbladder. Cholangitis can be acute or chronic, can result in partial or complete obstruction of the flow of bile. The infection of the bile is so common, that positive blood cultures are highly characteristic. In the case of a suppurative cholangitis with signs of sepsis treatment alone with antibiotics is usually not sufficient to achieve medical remission. Multiple hepatic abscesses are often present, and the mortality approaches 100% unless prompt endoscopic or surgical relief of the obstruction and drainage of infected bile are carried out. Endoscopic retrograde cholangiopancreatography ERCP with endoscopic sphincterotomy is the preferred initial procedure for both establishing a definitive diagnosis and providing effective therapy. Case description: We present the case of a 69-year-old female patient with complex chronic comorbidities who presented with acute cholangitis initially managed with endoscopically inserted stent and later complicated by sepsis and biloma formation. The bile was drained, and it showed an infection with Candida spp. requiring antifungal therapy. Conclusions: The failure to perform sphincterotomy in patients with suppurative cholangitis can contribute to the backflow of bile and worse outcomes. LEARNING POINTS: Biloma formation is a rare complication of biliary duct procedures and diseases such as cholangitis. A prompt identification of signs of complications in patients with disease of the biliary ducts is key in preventing clinical deterioration.Sphincterotomy is vital in the management of ascending cholangitis, as it prevents backflow of bile into the intrahepatic biliary system.The presence of multiple comorbidities in complex cases can become an obstacle to optimal management and drainage of septic bile.

Follow-Up Study of 17-ß Estradiol, Prolactin and Progesterone with the Kinetics and Prevalence of T. gondii Infection in Pregnant Women.

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. One-third of the world's population has come into contact with this parasite. In Mexico, the prevalence is between 15% and 50% in the general population and 34.9% in women with high-risk pregnancies. In pregnancy, the highest incidence of infection occurs in the third trimester and fetal damage is inversely proportional to gestational age. Maternal hormones play a fundamental role in the immune response. There are very few studies, with controversial results, on the levels of increased hormones and their relationship to the kinetics of T. gondii infections during pregnancy. The aim was to determine the serum levels of 17-ß estradiol, prolactin, and progesterone, and their association with anti-T. gondii antibodies' kinetics in pregnancy. Fifty-two pregnant patients were studied. A questionnaire with sociodemographic and clinical aspects was used. Afterward, 10 mL of venous blood was collected by venipuncture every trimester. The concentrations of 17-ß estradiol, progesterone, and prolactin were measured, using the ELISA method. In addition, anti-Toxoplasma IgG and IgM antibodies were also determined in the first, second, and third trimester. The prevalence of anti-Toxoplasma IgG antibodies was 26.92% in the first and second trimester and 32.7% in the third trimester. In seropositive women, 17-ß estradiol increased in the second and third trimesters of pregnancy. Progesterone increased significantly p < 0.039 in the third trimester in these women, while prolactin increased in the second trimester with a statistical significance of p < 0.021. In addition, 17-ß estradiol, progesterone, and prolactin are associated with T. gondii infection during pregnancy. New studies are necessary to clarify the specific mechanisms of immune response related to these hormones during pregnancy.

Characterization of a Trispecific PD-L1 Blocking Antibody That Exhibits EGFR-Conditional 4-1BB Agonist Activity.

Immune checkpoint blockade has changed the treatment paradigm for advanced solid tumors, but the overall response rates are still limited. The combination of checkpoint blockade with anti-4-1BB antibodies to stimulate tumor-infiltrating T cells has shown anti-tumor activity in human trials. However, the further clinical development of these antibodies has been hampered by significant off-tumor toxicities. Here, we generated an anti-4-1BB/EGFR/PD-L1 trispecific antibody consisting of a triple-targeting tandem trimerbody (TT) fused to an engineered silent Fc region. This antibody (IgTT-4E1-S) was designed to combine the blockade of the PD-L1/PD-1 axis with conditional 4-1BB costimulation specifically confined to the tumor microenvironment (TME). The antibody demonstrated simultaneous binding to purified EGFR, PD-L1, and 4-1BB in solution, effective blockade of the PD-L1/PD1 interaction, and potent 4-1BB-mediated costimulation, but only in the presence of EGFR-expressing cells. These results demonstrate the feasibility of IgTT-4E1-S specifically blocking the PD-L1/PD-1 axis and inducing EGFR-conditional 4-1BB agonist activity.

Body Awareness as a Protective Factor against Suicidal Orientations in College Students.

In this study, binary logistic regression and linear regression analyses were used to examine the relationship between interoceptive body awareness and suicidal orientation among Colombian university students. Additionally, the bootstrap technique was employed to resample and estimate the distribution of the data. The results support the idea that greater interoceptive awareness may protect against suicidal orientation by improving emotional regulation. An inverse relationship was found between interoceptive awareness and suicidal ideation. These findings align with previous literature emphasizing the importance of body awareness for emotional well-being. Further longitudinal research is needed to explore this relationship more deeply.

Optoelectronic Response to the Fluor Ion Bond on 4-(4,4,5,5-Tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde.

Boronate esters are a class of compounds containing a boron atom bonded to two oxygen atoms in an ester group, often being used as precursors in the synthesis of other materials. The characterization of the structure and properties of esters is usually carried out by UV-visible, infrared, and nuclear magnetic resonance (NMR) spectroscopic techniques. With the aim to better understand our experimental data, in this article, the density functional theory (DFT) is used to analyze the UV-visible and infrared spectra, as well as the isotropic shielding and chemical shifts of the hydrogen atoms 1H, carbon 13C and boron 11B in the compound 4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde. Furthermore, this study considers the change in its electronic and spectroscopic properties of this particular ester, when its boron atom is coordinated with a fluoride anion. The calculations were carried out using the LSDA and B3LYP functionals in Gaussian-16, and PBE in CASTEP. The results show that the B3LYP functional gives the best approximation to the experimental data. The formation of a coordinated covalent B-F bond highlights the remarkable sensitivity of the NMR chemical shifts of carbon, oxygen, and boron atoms and their surroundings. Furthermore, this bond also highlights the changes in the electron transitions bands n → π* and π → π* during the absorption and emission of a photon in the UV-vis, and in the stretching bands of the C=C bonds, and bending of BO2 in the infrared spectrum. This study not only contributes to the understanding of the properties of boronate esters but also provides important information on the interactions and responses optoelectronic of the compound when is bonded to a fluorine atom.

Characteristics and rates of infection by HIV in people receiving non-occupational post-exposure prophylaxis (nPEP) against HIV.

INTRODUCTION/OBJECTIVES: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters. METHODS: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment. RESULTS: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis. CONCLUSION: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.

Clinical Comparative Study of Shade Measurement Using Two Methods: Dental Guides and Spectrophotometry.

Tooth color is a determining factor in the fabrication of dental prostheses. The aim of the present study is to compare two measurement methods used in the field of dentistry: dental guides and spectrophotometry. A total of 2768 natural teeth were measured using the Vita Classical and Vita 3D-Master dental guides (Vita-Zahnfabrik, Bad Säckingen, Germany), as well as a Vita Easyshade Compact spectrophotometer (Vita-Zahnfabrik). The measurements were carried out by one operator under suitable illumination conditions at 5500 degrees Kelvin. The obtained results show that the measurements obtained with the Vita Classical dental guide classifies teeth into the A-B categories, while the spectrophotometer preferentially classifies teeth into the B-C categories. The correlation coefficients obtained with the dental guides ranged from -0.32 to -0.39 (p < 0.01), while those for the spectrophotometer ranged from -0.35 to -0.55 (p < 0.01). Therefore, we can conclude that the spectrophotometer is more reliable and reproducible in its measurements than the dental guides.

Mutual regulation of CD4+ T cells and intravascular fibrin in infections.

Innate myeloid cells especially neutrophils and their extracellular traps are known to promote intravascular coagulation and thrombosis formation in infections and various other conditions. Innate myeloid cell dependent fibrin formation can support systemic immunity while its dysregulation enhances the severity of infectious diseases. Less is known about the immune mechanisms preventing dysregulation of fibrin homeostasis in infection. During experimental systemic infections local fibrin deposits in the liver microcirculation cause rapid arrest of CD4+ T cells. Arrested T helper cells mostly represent Th17 cells that partially originate from the small intestine. Intravascular fibrin deposits activate mouse and human CD4+ T cells which can be mediated by direct fibrin - CD4+ T cell interactions. Activated CD4+ T cells suppress fibrin deposition and microvascular thrombosis by directly counteracting coagulation activation by neutrophils and classical monocytes. T cell activation, which is initially triggered by IL- 12p40- and MHC-II dependent mechanisms, enhances intravascular fibrinolysis via LFA-1. Moreover, CD4+ T cells disfavor the association of the fibrinolysis inhibitor TAFI with fibrin whereby fibrin deposition is increased by TAFI in the absence but not presence of T cells. In human infections thrombosis development is inversely related to microvascular levels of CD4+ T cells. Thus, fibrin promotes LFA-1 dependent T helper cell activation in infections which drives a negative feedback cycle that rapidly restricts intravascular fibrin and thrombosis development.

Facial trauma in the major league baseball.

OBJECTIVE: The objectives of this study were to identify and describe significant facial trauma present in Major League Baseball (MLB) that resulted in players missing games or being placed in the injury reserve list. STUDY DESIGN: This was a retrospective cohort study. The predictor variables were the player's age, height, weight, body mass index, position, team conference, and if played games took place in playoffs season. The outcome variables were injury location (upper, middle, and lower facial third) and type of injury (soft tissue, fracture). Chi-square and logistic regression were computed to determine associations between predictor and outcome variables. RESULTS: A total of 109 players missed games due to facial injuries, and a total of 115 injuries were identified. Of the 115 injuries, none occurred in the upper facial third, 96 (83%) were in the middle third, and 19 (17%) in the lower third. Most fractures occurred in fielders (45%), and most soft tissue injuries in basemen (40%). CONCLUSIONS: Significant facial trauma in the MLB has risen in recent years. The player's height, conference, and playoff season were the most associated factors. Most injuries occurred in the periorbital area. A recommendation for the use of protection goggles can be made to prevent them.