Older age is associated with a distinct and marked reduction of functionality of both alloreactive CD4+ and CD8+ T cells.

Introduction: Older recipient age is associated with a significant decreased risk for rejection after kidney transplantation which is incompletely understood. Methods: In a longitudinal study, circulating alloreactive T cells were assessed of young (≤45 years) and older (≥55 years) stable kidney transplant recipients. Alloreactive T-cells were identified by CD137-expression and phenotype, cytokine producing and proliferative capacity, were evaluated using multiparameter flowcytometry. Results: The results show that before transplantation frequencies of alloreactive CD4+ and CD8+ T-cells in older KT-recipients are significantly higher and shifted towards an effector memory-phenotype. However, the frequency of polyfunctional (≥2 pro-inflammatory cytokines) CD4+ T-cells was significantly lower and less IL2 was produced. The frequency of polyfunctional alloreactive CD4+ T-cells and proliferation of alloreactive T-cells donor-specifically declined after transplantation reaching a nadir at 12 months after transplantation, irrespective of age. A striking difference was observed for the proliferative response of alloreactive CD8+ T-cells. This was not only lower in older compared to younger recipients but could also not be restored by exogenous IL2 or IL15 in the majority of older recipients while the response to polyclonal stimulation was unaffected. Conclusion: In conclusion, older age is associated with a distinct and marked reduction of functionality of both alloreactive CD4+ and CD8+ T-cells.

The role of point-of-care ultrasound to monitor response of fluid replacement therapy in pregnancy.

Fluid management in obstetrical care is crucial because of the complex physiological conditions of pregnancy, which complicate clinical manifestations and fluid balance management. This expert review examined the use of point-of-care ultrasound to evaluate and monitor the response to fluid therapy in pregnant patients. Pregnancy induces substantial physiological changes, including increased cardiac output and glomerular filtration rate, decreased systemic vascular resistance, and decreased plasma oncotic pressure. Conditions, such as preeclampsia, further complicate fluid management because of decreased intravascular volume and increased capillary permeability. Traditional methods for assessing fluid volume status, such as physical examination and invasive monitoring, are often unreliable or inappropriate. Point-of-care ultrasound provides a noninvasive, rapid, and reliable means to assess fluid responsiveness, which is essential for managing fluid therapy in pregnant patients. This review details the various point-of-care ultrasound modalities used to measure dynamic changes in fluid status, focusing on the evaluation of the inferior vena cava, lung ultrasound, and left ventricular outflow tract. Inferior vena cava ultrasound in spontaneously breathing patients determines diameter variability, predicts fluid responsiveness, and is feasible even late in pregnancy. Lung ultrasound is crucial for detecting early signs of pulmonary edema before clinical symptoms arise and is more accurate than traditional radiography. The left ventricular outflow tract velocity time integral assesses stroke volume response to fluid challenges, providing a quantifiable measure of cardiac function, which is particularly beneficial in critical care settings where rapid and accurate fluid management is essential. This expert review synthesizes current evidence and practice guidelines, suggesting the integration of point-of-care ultrasound as a fundamental aspect of fluid management in obstetrics. It calls for ongoing research to enhance techniques and validate their use in broader clinical settings, aiming to improve outcomes for pregnant patients and their babies by preventing complications associated with both under- and overresuscitation.

Mental health priorities and cultural-responsiveness of the Mental Health First Aid (MHFA) training for Asian immigrant populations in Greater Boston, Massachusetts.

BACKGROUND: Asians and Asian Americans have the lowest rate of mental health service utilization (25%) in the US compared to other racial/ethnic groups (39 - 52%), despite high rates of depression, anxiety, and suicidal ideation. The lack of culturally-responsive mental health trainings hinders access to mental health services for these populations. We assessed the mental health priorities of Asian communities in Greater Boston and evaluated cultural responsiveness of the Mental Health First Aid (MHFA), a first-responder training teaching participants skills to recognize signs of mental health and substance use challenges, and how to appropriately respond. METHODS: This is community-based participatory research with the Boston Chinatown Neighborhood Center (BCNC), Asian Women For Health (AWFH), and the Addressing Disparities in Asian Populations through Translational Research (ADAPT) Coalition. We conducted focus groups with community-based organization staff and community members to assess mental health priorities of Asian populations in Boston, MA. We then evaluated the utility and cultural-responsiveness of the English-language MHFA for Asian populations through pre- and post-training questionnaires and focus groups with community participants. Paired t-tests were used to evaluate questionnaire responses. Thematic analysis was used to analyze interviews. RESULTS: In total, ten staff and eight community members participated in focus groups, and 24 community members completed the MHFA and pre- and post-training questionnaires. Common mental health challenges in the Asian communities reported by participants were loneliness, high stigma around mental illnesses, academic pressure, and acculturation stress. Compared to pre-training, MHFA participants demonstrated lower personal mental health stigma (p < 0.001) and higher mental health literacy (p = 0.04) post-training. Participants also noted the lack of data statistics and case studies relevant to Asian populations in the training, and desired the training be offered in languages spoken by Asian ethnic subgroups (e.g., Chinese, Vietnamese). CONCLUSION: Cultural-responsiveness of the MHFA for Asian populations could be improved with the inclusion of data and case studies that capture common mental health challenges in the Asian communities and with translation of the MHFA to non-English languages predominant in Asian communities. Increasing the cultural relevance and language accessibility of the MHFA could facilitate wider adoption of these trainings across communities and help to reduce mental health stigma and gaps in literacy and service utilization.

Responsive Acrylamide-Based Hydrogels: Advances in Interpenetrating Polymer Structures.

Hydrogels, composed of hydrophilic homopolymer or copolymer networks, have structures similar to natural living tissues, making them ideal for applications in drug delivery, tissue engineering, and biosensors. Since Wichterle and Lim first synthesized hydrogels in 1960, extensive research has led to various types with unique features. Responsive hydrogels, which undergo reversible structural changes when exposed to stimuli like temperature, pH, or specific molecules, are particularly promising. Temperature-sensitive hydrogels, which mimic biological processes, are the most studied, with poly(N-isopropylacrylamide) (PNIPAm) being prominent due to its lower critical solution temperature of around 32 °C. Additionally, pH-responsive hydrogels, composed of polyelectrolytes, change their structure in response to pH variations. Despite their potential, conventional hydrogels often lack mechanical strength. The double-network (DN) hydrogel approach, introduced by Gong in 2003, significantly enhanced mechanical properties, leading to innovations like shape-deformable DN hydrogels, organic/inorganic composites, and flexible display devices. These advancements highlight the potential of hydrogels in diverse fields requiring precise and adaptable material performance. In this review, we focus on advancements in the field of responsive acrylamide-based hydrogels with IPN structures, emphasizing the recent research on DN hydrogels.

Psychometric properties of patient-reported outcomes Common Terminology Criteria for adverse events (PRO-CTCAE®) in breast cancer patients: The prospective observational multicenter VIP study.

Patients' self-reporting is increasingly considered essential to measure quality-of-life and treatment-related side-effects. However, if multiple patient-reported instruments are used, redundancy may represent an overload for patients. Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) are a tool allowing direct patients' reporting of side-effects. We tested psychometric properties of a selected list of PRO-CTCAE items, in a cohort of 303 breast cancer patients, using validated instruments for quality of life assessment as anchors. The analysis of convergent validity with HADS (Hospital Anxiety and Depression Scale) and EORTC BR-23 sub-scales, and the analysis of responsiveness with the PGIC (Patients Global Impression of Change) score supported that a selected list of PRO-CTCAE symptoms might represent a standardized, agile tool for both research and practice settings to reduce patient burden without missing relevant information on patient perceptions. Among patients using digital devices, those with a higher education levels required shorter time to fulfil questionnaires. In conclusion, a selected list of PRO-CTCAE items can be considered as a standardized, agile tool for capturing crucial domains of side-effects and quality of life in patients with breast cancer. The study is registered on clinicaltrials.gov (NCT04416672).

Measurement properties of the Spanish COPM in older adult rehabilitation inpatients.

AIMS: To analyse the measurement properties of the Spanish version of the COPM (Canadian Occupational Performance Measure) in older adult rehabilitation inpatients. METHOD: A sample of 172 users from 17 inpatient care facilities for older adults (47% nursing homes) participated in a quantitative prospective study. We examined validity by correlating the COPM with the Barthel Index (BI), the Lawton Instrumental Activities of Daily Living scale (IADL), the EuroQol-five domains-three level questionnaire (EQ-5D-3L), and the Client-Centred Rehabilitation Questionnaire (CCRQ) and by examining associations with demographic variables. Reliability was evaluated through test-retest and responsiveness through differences in change scores in two types of care facilities. RESULTS: Participants prioritised 637 occupational performance problems, mainly in the area of self-care (70.5%). The COPM scale scores were significantly correlated with BI, IADL, EQ-5D-3L (except the pain dimension), and CCRQ (except the family involvement and continuity dimensions). COPM scores did not show statistically significant differences concerning educational level. Regarding reliability, high test-retest correlations were obtained (>.80). Nursing home users showed less responsiveness to rehabilitation than other users (change score < 2 vs. > 2 points). CONCLUSION AND SIGNIFICANCE: The Spanish COPM provides satisfactory measurement properties as a client-centred instrument in older adult rehabilitation inpatient.

Synthesis of Dual-Responsive Amphiphilic Glycomacromolecules: Controlled Release of Glycan Ligands via pH and UV Stimuli.

This work presents a versatile strategy for the synthesis of dual stimuli-responsive amphiphilic glycomacromolecules with tailored release properties. Amphiphilic precision glycomacromolecules (APGs) derived from tailor-made building blocks using solid phase polymer synthesis form glycofunctionalized micelles, a versatile class of materials with applications in drug delivery, as antiinfection agents as well as simple cell mimetics. In this work, this concept is extended by integrating cleavable building blocks into APGs now allowing stimuli-responsive release of glycan ligands or destruction of the micelles. This study incorporates a newly designed acid-labile building block, 4-(4-(((((9H-fluoren-9-yl)methoxy)carbonyl)amino)methyl)-1,3-dioxolan-2-yl)benzoic acid (DBA), suitable also for other types of solid phase or amide chemistry, and an established UV-cleavable 2-nitrobenzyl linker (PL). The results demonstrate that both linkers can be cleaved independently and thus allow dual stimuli-responsive release from the APG micelles. By choosing the APG design e.g., placing the cleavable linkers between glycomacromolecular blocks presenting different types of carbohydrates, they can tune APG and micellar stability as well as the interaction and cluster formation with a carbohydrate-recognizing lectin. Such dual-responsive glycofunctionalized micelles have wide potential for use in drug delivery applications or for the development as anti-adhesion agents in antiviral and antibacterial treatments.

Unravelling the role of tumor microenvironment responsive nanobiomaterials in spatiotemporal controlled drug delivery for lung cancer therapy.

Design and development of efficient drug delivery technologies that impart site-specificity is the need of the hour for the effective treatment of lung cancer. The emergence of materials science and nanotechnology partially helped drug delivery scientists to achieve this objective. Various stimuli-responsive materials that undergo degradation at the pathological tumor microenvironment (TME) have been developed and explored for drug delivery applications using nanotechnological approaches. Nanoparticles (NPs), owing to their small size and high surface area to volume ratio, demonstrated enhanced cellular internalization, permeation, and retention at the tumor site. Such passive accumulation of stimuli-responsive materials helped to achieve spatiotemporally controlled and targeted drug delivery within the tumors. In this review, we discussed various stimuli-physical (interstitial pressure, temperature, and stiffness), chemical (pH, hypoxia, oxidative stress, and redox state), and biological (receptor expression, efflux transporters, immune cells, and their receptors or ligands)-that are characteristic to the TME. We mentioned an array of biomaterials-based nanoparticulate delivery systems that respond to these stimuli and control drug release at the TME. Further, we discussed nanoparticle-based combinatorial drug delivery strategies. Finally, we presented our perspectives on challenges related to scale-up, clinical translation, and regulatory approvals.

Transient secondary pseudo-hypoaldosteronism in infants with urinary tract infections: systematic literature review.

Infants with a congenital anomaly of the kidney and urinary tract sometimes present with hyponatremia, hyperkalemia, and metabolic acidosis due to under-responsiveness to aldosterone, hereafter referred to as secondary pseudo-hypoaldosteronism. The purpose of this report is to investigate pseudo-hypoaldosteronism in infant urinary tract infection. A systematic review was conducted following PRISMA guidelines after PROSPERO (CRD42022364210) registration. The National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar without limitations were used. Inclusion criteria involved pediatric cases with documented overt pseudo-hypoaldosteronism linked to urinary tract infection. Data extraction included demographics, clinical features, laboratory parameters, management, and course. Fifty-seven reports were selected, detailing 124 cases: 95 boys and 29 girls, 10 months or less of age (80% of cases were 4 months or less of age). The cases exhibited hyponatremia, hyperkalemia, acidosis, and activated renin-angiotensin II-aldosterone system. An impaired kidney function was found in approximately every third case. Management included antibiotics, fluids, and, occasionally, emergency treatment of hyperkalemia, hyponatremia, or acidosis. The recovery time averaged 1 week for electrolyte, acid-base imbalance, and kidney function. Notably, anomalies of the kidney and urinary tract were identified in 105 (85%) cases. CONCLUSIONS: This review expands the understanding of overt transient pseudo-hypoaldosteronism complicating urinary tract infection. Management involves antimicrobials, fluid replacement, and consideration of electrolyte imbalances. Raising awareness of this condition within pediatric hospitalists is desirable. WHAT IS KNOWN: • Infants affected by a congenital anomaly of the kidney and urinary tract may present with clinical and laboratory features resembling primary pseudo-hypoaldosteronism. • Identical features occasionally occur in infant urinary tract infection. WHAT IS NEW: • Most cases of secondary pseudo-hypoaldosteronism associated with a urinary tract infection are concurrently affected by a congenital anomaly of the kidney and urinary tract. • Treatment with antibiotics and parenteral fluids typically results in the normalization of sodium, potassium, bicarbonate, and creatinine within approximately 1 week.

Effects of acute stress on reward processing: A comprehensive meta-analysis of rodent and human studies.

Stressors can initiate a cascade of central and peripheral changes that modulate mesocorticolimbic dopaminergic circuits and, ultimately, behavioral response to rewards. Driven by the absence of conclusive evidence on this topic and the Research Domain Criteria framework, random-effects meta-analyses were adopted to quantify the effects of acute stressors on reward responsiveness, valuation, and learning in rodent and human subjects. In rodents, acute stress reduced reward responsiveness (g = -1.43) and valuation (g = -0.32), while amplifying reward learning (g = 1.17). In humans, acute stress had marginal effects on valuation (g = 0.25), without affecting responsiveness and learning. Moderation analyses suggest that acute stress neither has unitary effects on reward processing in rodents nor in humans and that the duration of the stressor and specificity of reward experience (i.e., food vs drugs) may produce qualitatively and quantitatively different behavioral endpoints. Subgroup analyses failed to reduce heterogeneity, which, together with the presence of publication bias, pose caution on the conclusions that can be drawn and point to the need of guidelines for the conduction of future studies in the field.

Assessing aspects of early social communication in non-speaking children with bilateral cerebral palsy.

PURPOSE: Research suggests that rates for autism may be higher in cerebral palsy than in the general population. For those with severe bilateral physical impairment (GMFCS level IV and V) and little or no speech, describing a profile of social communication skills has been difficult because there are currently no assessments for early social communication specifically tailored for these children. Our aim was to explore the assessment of aspects of joint attention and social reciprocity in this group of children with CP. METHODS: We compared the performance of children with bilateral CP on carefully designed assessments of joint attention and social responsiveness with groups of children with Down syndrome and autism. All three groups were matched for chronological age and mental age. RESULTS: Approximately 30% of the children with bilateral CP had early social communication scores similar to the autistic children. The remaining 70% of children with CP had a range of early social communication scores similar to the children with Down syndrome. CONCLUSION: It is possible to assess key early social communication skills in non-speaking children with bilateral motor disability. This could provide insights to help clinicians and caregivers as they discuss abilities and explore potential areas for intervention.

With carefully designed activities, which do not rely on motor skills or verbal exchanges, it was possible to assess joint attention and social responsiveness skills in a group of non-speaking children with bilateral motor disability.We were able to identify a subgroup of non-speaking children with severe motor disability (approximately 30% of our cohort) whose scores on our assessments were similar to a group of autistic children.The ability to describe key early social communication skills should provide insights to help clinicians and caregivers as they discuss abilities and explore potential areas for intervention.

Stroke volume variation induced by lung recruitment maneuver to predict fluid responsiveness in patients receiving mechanical ventilation: A systematic review and meta-analysis.

STUDY OBJECTIVE: The aim of this study was to evaluate the accuracy of lung recruitment maneuver induced stroke volume variation (ΔSVLRM) in predicting fluid responsiveness in mechanically ventilated adult patients by systematic review and meta-analysis. METHODS: A comprehensive electronic search of relevant literature was conducted in PubMed, Web of Science, Cochrane Library, Ovid Medline, Embase and Chinese databases (including China National Knowledge Infrastructure, Wanfang and VIP databases). Review Manager 5.4, Meta-DiSc 1.4 and STATA 16.0 were selected for data analysis, and QUADAS-2 tool was used for quality assessment. Data from selected studies were pooled to obtain sensitivity, specificity, diagnostic likelihood ratio (DLR) of positive and negative, diagnostic odds ratio (DOR), and summary receiver operating characteristic curve. RESULTS: A total of 6 studies with 256 patients were enrolled through March 2024. The risk of bias and applicability concerns for each included study were low, and there was no significant publication bias. There was moderate to substantial heterogeneity for the non-threshold effect, but not for the threshold effect. The combined sensitivity and specificity were 0.84 (95% CI, 0.77-0.90) and 0.79 (95% CI, 0.70-0.86), respectively. The DOR and the area under the curve (AUC) were 22.15 (95%CI, 7.62-64.34) and 0.90 (95% CI, 0.87-0.92), respectively. The positive and negative predictive values of DLR were 4.53 (95% CI, 2.50-8.18) and 0.19 (95% CI, 0.11-0.35), respectively. Fagan's nomogram showed that with a pre-test probability of 52%, the post-test probability reached 83% and 17% for the positive and negative tests, respectively. CONCLUSIONS: Based on the currently available evidence, ΔSVLRM has a good diagnostic value for predicting the fluid responsiveness in adult patients undergoing mechanical ventilation. Given the heterogeneity and limitations of the published data, further studies with large sample sizes and different clinical settings are needed to confirm the diagnostic value of ΔSVLRM in predicting fluid responsiveness. PROSPERO registration number: CRD42023490598.

Bioinformatics analysis of an immunotherapy responsiveness-related gene signature in predicting lung adenocarcinoma prognosis.

Background: Immune therapy has become first-line treatment option for patients with lung cancer, but some patients respond poorly to immune therapy, especially among patients with lung adenocarcinoma (LUAD). Novel tools are needed to screen potential responders to immune therapy in LUAD patients, to better predict the prognosis and guide clinical decision-making. Although many efforts have been made to predict the responsiveness of LUAD patients, the results were limited. During the era of immunotherapy, this study attempts to construct a novel prognostic model for LUAD by utilizing differentially expressed genes (DEGs) among patients with differential immune therapy responses. Methods: Transcriptome data of 598 patients with LUAD were downloaded from The Cancer Genome Atlas (TCGA) database, which included 539 tumor samples and 59 normal control samples, with a mean follow-up time of 29.69 months (63.1% of patients remained alive by the end of follow-up). Other data sources including three datasets from the Gene Expression Omnibus (GEO) database were analyzed, and the DEGs between immunotherapy responders and nonresponders were identified and screened. Univariate Cox regression analysis was applied with the TCGA cohort as the training set and GSE72094 cohort as the validation set, and least absolute shrinkage and selection operator (LASSO) Cox regression were applied in the prognostic-related genes which fulfilled the filter criteria to establish a prognostic formula, which was then tested with time-dependent receiver operating characteristic (ROC) analysis. Enriched pathways of the prognostic-related genes were analyzed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and tumor immune microenvironment (TIME), tumor mutational burden, and drug sensitivity tests were completed with appropriate packages in R (The R Foundation of Statistical Computing). Finally, a nomogram incorporating the prognostic formula was established. Results: A total of 1,636 DEGs were identified, 1,163 prognostic-related DEGs were extracted, and 34 DEGs were selected and incorporated into the immunotherapy responsiveness-related risk score (IRRS) formula. The IRRS formula had good performance in predicting the overall prognoses in patients with LUAD and had excellent performance in prognosis prediction in all LUAD subgroups. Moreover, the IRRS formula could predict anticancer drug sensitivity and immunotherapy responsiveness in patients with LUAD. Mechanistically, immune microenvironments varied profoundly between the two IRRS groups; the most significantly varied pathway between the high-IRRS and low-IRRS groups was ribonucleoprotein complex biogenesis, which correlated closely with the TP53 and TTN mutation burdens. In addition, we established a nomogram incorporating the IRRS, age, sex, clinical stage, T-stage, N-stage, and M-stage as predictors that could predict the prognoses of 1-year, 3-year, and 5-year survival in patients with LUAD, with an area under curve (AUC) of 0.718, 0.702, and 0.68, respectively. Conclusions: The model we established in the present study could predict the prognosis of LUAD patients, help to identify patients with good responses to anticancer drugs and immunotherapy, and serve as a valuable tool to guide clinical decision-making.

Changes of pulse wave transit time after haemodynamic manoeuvres in healthy adults: a prospective randomised observational trial (PWTT volunteer study).

Background: Pulse wave transit time (PWTT) shows promise for monitoring intravascular fluid status intraoperatively. Presently, it is unknown how PWTT mirrors haemodynamic variables representing preload, inotropy, or afterload. Methods: PWTT was measured continuously in 24 adult volunteers. Stroke volume was assessed by transthoracic echocardiography. Volunteers underwent four randomly assigned manoeuvres: 'Stand-up' (decrease in preload), passive leg raise (increase in preload), a 'step-test' (adrenergic stimulation), and a 'Valsalva manoeuvre' (increase in intrathoracic pressure). Haemodynamic measurements were performed before and 1 and 5 min after completion of each manoeuvre. Correlations between PWTT and stroke volume were analysed using the Pearson correlation coefficient. Results: 'Stand-up' caused an immediate increase in PWTT (mean change +55.9 ms, P-value <0.0001, 95% confidence interval 46.0-65.7) along with an increase in mean arterial pressure and heart rate and a drop in stroke volume (P-values <0.0001). Passive leg raise caused an immediate drop in PWTT (mean change -15.4 ms, P-value=0.0024, 95% confidence interval -25.2 to -5.5) along with a decrease in mean arterial pressure (P-value=0.0052) and an increase in stroke volume (P-value=0.001). After 1 min, a 'step-test' caused no significant change in PWTT measurements (P-value=0.5716) but an increase in mean arterial pressure and heart rate (P-values <0.0001), without changes in stroke volume (P-value=0.1770). After 5 min, however, PWTT had increased significantly (P-value <0.0001). Measurements after the Valsalva manoeuvre caused heterogeneous results. Conclusion: Noninvasive assessment of PWTT shows promise to register immediate preload changes in healthy adults. The clinical usefulness of PWTT may be hampered by late changes because of reasons different from fluid shifts. Clinical trial registration: German clinical trial register (DRKS, ID: DRKS00031978, https://www.drks.de/DRKS00031978).

Reliability, Measurement Error, and Responsiveness of the Voice Handicap Index: A Systematic Review and Meta-analysis.

OBJECTIVE: To analyze the reliability, measurement error, and responsiveness of the Voice Handicap Index (VHI) for measuring voice handicap in individuals with voice disorders. METHODS: This systematic review followed the recommendations of the COnsensus-based Standards for the Selection of Health Measurement INstruments. Studies that validated the VHI, analyzed the measurement properties of reliability, measurement error, or responsiveness, and had dysphonic individuals as the study population were included. The following electronic databases were searched: Cochrane Library, EMBASE, LILACS, PubMed, Scopus, and Web of Science. The manual search was carried out on gray literature in the Biblioteca Digital Brasileira de Teses e Dissertações and ProQuest Dissertation & Theses, in addition to mapping citations and consulting an expert in the field. Evidence selection, data extraction, risk of bias analysis, certainty of evidence, and good psychometric measurements were performed by two blinded and independent reviewers. A meta-analysis was performed using Fisher's transformed r-to-z correlation coefficient and standardized mean difference. Heterogeneity was calculated using Tau² and I² statistical tests in JAMOVI 2.3.2 software. RESULTS: Eighty studies were included in the meta-analysis. When assessing the risk of bias, most studies were classified as inadequate during the reliability and measurement error stages. In the responsiveness stage, they were classified as doubtful in the sensitivity and specificity sub-boxes and good in the comparison sub-box with a gold standard instrument. For psychometric properties, most studies were classified as indeterminate in terms of both reliability and responsiveness. In test-retest reliability and responsiveness, the average outcome differed significantly from zero, indicating agreement between the test and retest moments and a significant reduction in the VHI score after intervention. Considering certainty of the evidence, the level of evidence was very low in both the reliability and responsiveness stages. The analyzed studies did not evaluate observational errors, and hence, they were not considered in this review. CONCLUSION: The VHI proved to be reliable and responsive in measuring voice handicap. However, it should be used with caution, as there is heterogeneity, a risk of bias, and no adherence to the analysis of observational error.

Primary hyperoxaluria: Long-term outcomes of isolated kidney versus simultaneous liver/kidney transplant.

OBJECTIVES: To compare long-term transplant outcomes (organ rejection and retransplant) of simultaneous liver/kidney transplant (SLK) versus isolated kidney transplant (IK) for patients with primary hyperoxaluria (PH). METHODS: The Rare Kidney Stone Consortium PH registry was queried to identify patients with PH who underwent SLK or IK from 1999 to 2021. Patient characteristics and long-term transplant outcomes were abstracted and analyzed. Statistical comparisons were performed with Kaplan-Meier plots and Cox proportional hazards models. RESULTS: We identified 250 patients with PH, of whom 35 received care at Mayo Clinic and underwent SLK or IK. Patients who underwent SLK as their index transplant had lower odds of kidney rejection than did those who underwent IK (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.08-0.99; p = .048). The immunoprotective effect of concomitant liver and kidney transplant appeared to enhance outcomes for patients with PH. Additionally, the odds of retransplant were significantly lower for patients who underwent SLK as their index transplant than for those who underwent IK (HR, 0.08; 95% CI, 0.02-0.42; p = .003). Of five patients who underwent IK and had maintained graft function for at least 5 years after transplant, three (60%) had documented vitamin B6 responsiveness. CONCLUSIONS: Patients with PH who underwent SLK had a lower risk of kidney rejection and retransplant than those who underwent IK. Accurate genetic assessment for vitamin B6 responsiveness may optimize IK allocation. Novel therapeutics, such as lumasiran, have been introduced as promising agents for the management of PH.

Responsiveness and minimal important change of specific and generic patient-reported outcome measures for back patients: the Norwegian Neck and Back Register.

PURPOSE: To evaluate responsiveness and minimal important change (MIC) of Oswestry Disability Index (ODI), pain during activity on a numeric rating scale (NRSa) and health related quality of life (EQ-5D) based on data from the Norwegian neck and back registry (NNRR). METHODS: A total of 1617 patients who responded to NNRR follow-up after both 6 and 12 months were included in this study. Responsiveness was calculated using standardized response mean and area under the receiver operating characteristic (ROC) curve. We calculated MIC with both an anchor-based and distribution-based method. RESULTS: The condition specific ODI had best responsiveness, the more generic NRSa and EQ-5D had lower responsiveness. We found that the MIC for ODI varied from 3.0 to 9.5, from 0.4 to 2.5 for NRSa while the EQ5D varied from 0.05 to 0.12 depending on the method for calculation. CONCLUSION: In a register based back pain population, the condition specific ODI was more responsive to change than the more generic tools NRSa and EQ5D. The variations in responsiveness and MIC estimates also indicate that they should be regarded as indicative, rather than fixed estimates.

Pushing Trap-Controlled Persistent Luminescence Materials toward Multi-Responsive Smart Platforms: Recent Advances, Mechanism, and Frontier Applications.

Smart stimuli-responsive persistent luminescence materials, combining the various advantages and frontier applications prospects, have gained booming progress in recent years. The trap-controlled property and energy storage capability to respond to external multi-stimulations through diverse luminescence pathways make them attractive in emerging multi-responsive smart platforms. This review aims at the recent advances in trap-controlled luminescence materials for advanced multi-stimuli-responsive smart platforms. The design principles, luminescence mechanisms, and representative stimulations, i.e., thermo-, photo-, mechano-, and X-rays responsiveness, are comprehensively summarized. Various emerging multi-responsive hybrid systems containing trap-controlled luminescence materials are highlighted. Specifically, temperature dependent trapping and de-trapping performance is discussed, from extreme-low temperature to ultra-high temperature conditions. Emerging applications and future perspectives are briefly presented. It is hoped that this review would provide new insights and guidelines for the rational design and performance manipulation of multi-responsive materials for advanced smart platforms.

Autistic traits in youth with familial adenomatous polyposis: A Dutch-Canadian case-control study.

This study investigated the neurodevelopmental impact of pathogenic adenomatous polyposis coli (APC) gene variants in patients with familial adenomatous polyposis (FAP), a cancer predisposition syndrome. We hypothesized that certain pathogenic APC variants result in behavioral-cognitive challenges. We compared 66 FAP patients (cases) and 34 unaffected siblings (controls) to explore associations between APC variants and behavioral and cognitive challenges. Our findings indicate that FAP patients exhibited higher Social Responsiveness Scale (SRS) scores, suggesting a greater prevalence of autistic traits when compared to unaffected siblings (mean 53.8 vs. 47.4, Wilcoxon p = 0.018). The distribution of SRS scores in cases suggested a bimodal pattern, potentially linked to the location of the APC variant, with scores increasing from the 5' to 3' end of the gene (Pearson's r = 0.33, p = 0.022). While we observed a trend toward lower educational attainment in cases, this difference was not statistically significant. This study is the first to explore the connection between APC variant location and neurodevelopmental traits in FAP, expanding our understanding of the genotype-phenotype correlation. Our results emphasize the importance of clinical assessment for autistic traits in FAP patients, shedding light on the potential role of APC gene variants in these behavioral and cognitive challenges.

Demonstrating responsiveness of the pediatric cardiac quality of life inventory in children and adolescents undergoing arrhythmia ablation, heart transplantation, and valve surgery.

PURPOSE: Pediatric Cardiac Quality of Life Inventory (PCQLI) is a disease-specific pediatric cardiac health-related quality of life (HRQOL) instrument that is reliable, valid, and generalizable. We aim to demonstrate PCQLI responsiveness in children undergoing arrhythmia ablation, heart transplantation, and valve surgery before and after cardiac intervention. METHODS: Pediatric cardiac patients 8-18 years of age from 11 centers undergoing arrhythmia ablation, heart transplantation, or valve surgery were enrolled. Patient and parent-proxy PCQLI Total, Disease Impact and Psychosocial Impact subscale scores were assessed pre- and 3-12 months follow-up. Patient clinical status was assessed by a clinician post-procedure and dichotomized into markedly improved/improved and no change/worse/much worse. Paired t-tests examined change over time. RESULTS: We included 195 patient/parent-proxies: 12.6 ± 3.0 years of age; median follow-up time 6.7 (IQR = 5.3-8.2) months; procedural groups - 79 (41%) ablation, 28 (14%) heart transplantation, 88 (45%) valve surgery; clinical status - 164 (84%) markedly improved/improved, 31 (16%) no change/worse/much worse. PCQLI patient and parent-proxies Total scores increased (p ≤ 0.013) in each intervention group. All PCQLI scores were higher (p < 0.001) in the markedly improved/improved group and there were no clinically significant differences in the PCQLI scores in the no difference/worse/much worse group. CONCLUSION: The PCQLI is responsive in the pediatric cardiac population. Patients with improved clinical status and their parent-proxies reported increased HRQOL after the procedure. Patients with no improvement in clinical status and their parent-proxies reported no change in HRQOL. PCQLI may be used as a patient-reported outcome measure for longitudinal follow-up and interventional trials to assess HRQOL impact from patient and parent-proxy perspectives.

It is important to have quality of life (QOL) measures that are sensitive to change in QOL before and after procedures and to be sensitive to change over time. The Pediatric Cardiac Quality of Life Inventory (PCQLI) is a QOL measure specifically developed for children with cardiac disease. This study assessed the responsiveness of the PCQLI to detect change in QOL over time. QOL in Children and adolescents who were being treated for abnormal heart rhythms, heart transplantation, and aortic, pulmonary, or mitral valve surgery were assessed before and after their procedure. Children and adolescents with improved clinical status post-procedure, and their parents, reported better QOL after the procedure. Patients with no improvement from a cardiac standpoint and their parents reported no change in QOL after their procedure. The PCQLI may be used to assess QOL before and after cardiac procedures or medical treatment and follow QOL over time.