Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis.

Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10-5) and MSK-IMPACT cohorts (p-value = 3.062 × 10-2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients.

RNA aggregates harness the danger response for potent cancer immunotherapy.

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.

Backup Frontal Drainage System for Urgent Tension Pneumocephalus Management After Chronic Subdural Hematoma Surgery: A Retrospective Cohort Study.

OBJECTIVE: To describe a simple variation of burr hole craniostomy for the management of chronic subdural hematoma (CSDH) that uses a frontal drainage system to facilitate timely decompression in the event of tension pneumocephalus and spares the need for additional surgery. METHODS: We conducted a retrospective analysis of 20 patients with CSDH who underwent burr hole craniostomy and 20 patients who underwent the same procedure alongside the placement of a 5 Fr neonatal feeding tube as a backup drainage for the anterior craniostomy. Depending on the situation, the secondary drain stayed for a maximum of 72 hours to be opened and used in emergency settings for drainage, aspiration, or as a 1-way valve with a water seal. RESULTS: The outcomes of 20 patients who underwent this procedure and 20 controls are described. One patient from each group presented tension pneumocephalus. One was promptly resolved by opening the backup drain under a water seal to evacuate pneumocephalus and the other patient had to undergo a reopening of the craniostomy. CONCLUSIONS: The described variation of burr hole craniostomy represents a low-cost and easy-to-implement technique that can be used for emergency decompression of tension pneumocephalus. It also has the potential to reduce reoperation rates and CSDH recurrence. Prospective controlled research is needed to validate this approach further.

Incarceration history and opioid use among adults living with HIV and chronic pain: a secondary analysis of a prospective cohort study.

BACKGROUND: Adults living with HIV have disproportionately high chronic pain, prescription opioid use, history of substance use, and incarceration. While incarceration can have long-lasting health impacts, prior studies have not examined whether distant (>1 year prior) incarceration is associated with opioid use for chronic pain, or with opioid misuse or opioid use disorder among people living with HIV and chronic pain. METHODS: We conducted a secondary analysis of a prospective cohort study of adults living with HIV and chronic pain. The independent variables were any distant incarceration and drug-related distant incarceration (both dichotomous). Dependent variables were current long-term opioid therapy, current opioid misuse, and current opioid use disorder. A series of multivariate logistic regression models were conducted, adjusting for covariates. RESULTS: In a cohort of 148 participants, neither distant incarceration nor drug-related incarceration history were associated with current long-term opioid therapy. Distant incarceration was associated with current opioid misuse (AOR 3.28; 95% CI: 1.41-7.61) and current opioid use disorder (AOR 4.40; 95% CI: 1.54-12.56). Drug-related incarceration history was also associated with current opioid misuse (AOR 4.31; 95% CI: 1.53-12.17) and current opioid use disorder (AOR 7.28; 95% CI: 2.06-25.71). CONCLUSIONS: The positive associations of distant incarceration with current opioid misuse and current opioid use disorder could indicate a persistent relationship between incarceration and substance use in people living with HIV and chronic pain. Additional research on opioid use among formerly incarcerated individuals in chronic pain treatment is needed.

Frailty in severe COVID-19 survivors after ICU admission. A prospective and multicenter study in Mexico.

OBJECTIVE: To analyze the presence of frailty in survivors of severe COVID-19 admitted in the Intensive Care Unit (ICU) and followed six months after discharge. DESIGN: An observational, prospective and multicenter, nation-wide study. SETTING: Eight adult ICU across eight academic acute care hospitals in Mexico. PATIENTS: All consecutive adult COVID-19 patients admitted in the ICU with acute respiratory failure between March 8, 2020 to February 28, 2021 were included. Frailty was defined according to the FRAIL scale, and was obtained at ICU admission and 6-month after hospital discharge. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: The primary endpoint was the frailty status 6-months after discharge. A regression model was used to evaluate the predictors during ICU stay associated with frailty. RESULTS: 196 ICU survivors were evaluated for basal frailty at ICU admission and were included in this analysis. After 6-months from discharge, 164 patients were evaluated for frailty: 40 patients (20.4%) were classified as non-frail, 67 patients (34.2%) as pre-frail and 57 patients (29.1%) as frail. After adjustment, the need of invasive mechanical ventilation was the only factor independently associated with frailty at 6 month follow-up (Odds Ratio [OR] 3.70, 95% confidence interval 1.40-9.81, P = .008). CONCLUSIONS: Deterioration of frailty was reported frequently among ICU survivors with severe COVID-19 at 6-months. The need of invasive mechanical ventilation in ICU survivors was the only predictor independently associated with frailty.

Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines.

Introduction: One of the primary obstacles faced by individuals with advanced colorectal cancer (CRC) is the potential development of acquired chemoresistance as the disease advances. Studies have indicated a direct association between elevated levels of miR-92a-3p and the progression, metastasis, and chemoresistance observed in CRC. We proposed that miR-92a-3p impairs FOLFOX (fluorouracil/oxaliplatin) chemotherapy response by upregulating the expression of chemoresistance biomarker genes through the activation of ß-catenin and epithelial-mesenchymal transition (EMT). These FOLFOX biomarker genes include the pyrimidine biosynthesis pathway genes dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and the genes encoding the DNA repair complexes subunits ERCC1 and ERCC2, and XRCC1. Methods: To assess this, we transfected SW480 and SW620 colon cancer cell lines with miR-92a-3p mimics and then quantified the expression of DPYD, TYMS, MTHFR, ERCC1, ERCC2, and XRCC1, the expression of EMT markers and transcription factors, and activation of ß-catenin. Results and discussion: Our results reveal that miR-92a-3p does not affect the expression of DPYD, TYMS, MTHFR, and ERCC1. Furthermore, even though miR-92a-3p affects ERCC2, XRCC1, E-cadherin, and ß-catenin mRNA levels, it has no influence on their protein expression. Conclusion: We found that miR-92a-3p does not upregulate the expression of proteins of DNA-repair pathways and other genes involved in FOLFOX chemotherapy resistance.

De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a novel syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 119 individuals with NDD. The vast majority of individuals (77.3%) have the same highly recurrent single base-pair insertion (n.64_65insT). We estimate that variants in this region explain 0.41% of individuals with NDD. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to its contiguous counterpart RNU4-1 and other U4 homologs, supporting RNU4-2's role as the primary U4 transcript in the brain. Overall, this work underscores the importance of non-coding genes in rare disorders. It will provide a diagnosis to thousands of individuals with NDD worldwide and pave the way for the development of effective treatments for these individuals.

Adverse Childhood Experiences and Sleep Disturbances Among Puerto Rican Young Adults.

Importance: Sleep quality is a known marker of overall health. Studies suggest that adverse childhood experiences (ACEs) are associated with sleep disturbances among children and adults. Objective: To examine the association of retrospective and prospective ACEs with sleep quality among a cohort of Puerto Rican young adults from 2 sociocultural contexts. Design, Setting, and Participants: This prospective cohort study used data from the Boricua Youth Study (BYS), a population-based study representing Puerto Rican children from the South Bronx, New York, and Puerto Rico conducted from August 2000 to August 2003. Participants who were 5 to 9 years of age at enrollment in the BYS and who participated in wave 4 of the BYS took part in the Health Assessment (HA) when they were 18 to 29 years of age, from April 2013 to August 2017. Of the eligible 982 participants, 813 (82.8%) participated in the HA. Statistical analysis was conducted from January 2023 to January 2024. Exposures: Prospective ACEs measured from parent and youth responses and retrospective ACEs measured among young adults using questions from the validated ACE questionnaire from the original ACEs study conducted by Kaiser Permanente and the Centers for Disease Control and Prevention and published in 1998. Analysis included 8 overlapping items from both questionnaires. Outcomes: Sleep quality was assessed in the HA with the Pittsburgh Sleep Quality Index. The summary score included 7 components of the Pittsburgh Sleep Quality Index. The hypothesis was formulated after data collection. Sleep quality information was gathered at the same time as retrospective ACEs in the HA. Results: Of the 813 participants, 438 (53.9%) lived in Puerto Rico as children, 411 (50.6%) identified as female, and the mean (SE) age of participants was 22.9 (0.07) years. After adjusting for sociodemographic factors, retrospective ACEs had a significant association with worse sleep outcomes (ß [SE] = 0.29 [0.07]; 95% CI, 0.15-0.44; P < .001). Prospective ACEs did not have a significant association with sleep quality, after adjusting for sociodemographic factors (ß [SE] = 0.05 [0.10]; 95% CI, -0.14 to 0.24; P = .59). Conclusions and Relevance: This study suggests that there is a significant association between retrospective ACEs and sleep quality among Puerto Rican young adults, after adjusting for sociodemographic factors. Prospective ACEs were not significantly associated with sleep disturbances, after adjusting for sociodemographic factors. Addressing ACEs reported in young adulthood may help reduce sleep disorders.

Self-reported neighborhood stressors and sleep quality among Puerto Rican young adults.

OBJECTIVE: To examine the association between changes in self-reported neighborhood stressors and sleep quality and determine whether this varied by sociocultural context among Puerto Rican young adults. METHODS: Data come from the Boricua Youth Study Health Assessment, a sample of Puerto Rican young adults from San Juan, Puerto Rico, and South Bronx, New York (n = 818; mean age=22.9years). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Neighborhood social stressors (disorder, social cohesion, and safety) were parent-reported in childhood and self-reported in young adulthood and categorized into: low in childhood/young adulthood (reference group), high in childhood/low in young adulthood, low in childhood/high in young adulthood, and high in childhood/young adulthood. Sociocultural context was based on participant residence during childhood (San Juan vs. South Bronx). RESULTS: Adjusting for sociodemographic factors, living with high neighborhood stressors in both childhood and young adulthood (prevalence ratios=1.30, 95% CI: 1.01, 1.66) was associated with overall poor sleep (PSQI score >5). Among PSQI components, living with high neighborhood stressors in young adulthood only or in both time periods was associated with worse subjective sleep quality and daytime dysfunction. Additionally, there were various associations between the neighborhood stressor measures and PSQI components. Results did not differ by sociocultural context. CONCLUSION: Findings suggest that living with high levels of neighborhood stressors during childhood and young adulthood may have a cumulative adverse impact on sleep quality in young adulthood.

Epidemiological and clinical description of patients with oropharyngeal cancer treated in a public oncology referral hospital in Chile.

Introduction: The incidence of squamous carcinoma of the oropharynx (OPSCC) has presented an increase worldwide, a fact that occurs along with a phenomenon of epidemiological transition, whose pathogenesis is linked to human papilloma virus (HPV) in a significant part of the cases. Published evidence at the Latin American level is scarce. The present study aims to evaluate the epidemiological and clinical characteristics of patients with oropharyngeal cancer treated in a public oncology reference centre in Chile. Methodology: A cross-sectional study was carried out. Patients with histological confirmation of OPSCC aged 18 years or older, referred to the National Cancer Institute of Chile between 2012 and 2023 were included. The association with HPV was determined by immunohistochemistry for p16. Results: 178 patients were analysed, most of them in locoregionally advanced stages involving the palatine tonsil. Seventy-seven percent were male, with a median age of 60 years. Sixty-seven percent of patients were positive for p16, with a progressive increase to 85% in the last 2 years of the study. The p16(+) patients were younger and had fewer classical risk factors. Primary treatment was radiotherapy in 94% of patients. Conclusion: The epidemiological profile of patients with OPSCC treated in a Chilean public oncology referral centre reflects the epidemiological transition observed in developed countries. This change justifies the need to adapt health policies and conduct research that considers the characteristics of this new epidemiological profile.

Comparison of Contemporary Risk Scores in All Groups of Pulmonary Hypertension: A Pulmonary Vascular Research Institute GoDeep Meta-Registry Analysis.

BACKGROUND: Pulmonary hypertension (PH) is a heterogeneous disease with a poor prognosis. Accurate risk stratification is essential for guiding treatment decisions in pulmonary arterial hypertension (PAH). Although various risk models have been developed for PAH, their comparative prognostic potential requires further exploration. Additionally, the applicability of risk scores in PH groups beyond group 1 remains to be investigated. RESEARCH QUESTION: Are risk scores originally developed for PAH predictive in PH groups 1 through 4? STUDY DESIGN AND METHODS: We conducted a comprehensive analysis of outcomes among patients with incident PH enrolled in the multicenter worldwide Pulmonary Vascular Research Institute GoDeep meta-registry. Analyses were performed across PH groups 1 through 4 and further subgroups to evaluate the predictive value of PAH risk scores, including REVEAL Lite 2, REVEAL 2.0, ESC/ERS 2022, COMPERA 3-strata, and COMPERA 4-strata. RESULTS: Eight thousand five hundred sixty-five patients were included in the study, of whom 3,537 patients were assigned to group 1 PH, whereas 1,807 patients, 1,635 patients, and 1,586 patients were assigned to group 2 PH, group 3 PH, and group 4 PH, respectively. Pulmonary hemodynamics were impaired with median mean pulmonary arterial pressure of 42 mm Hg (33-52 mm Hg) and pulmonary vascular resistance of 7 WU (4-11 WU). All risk scores were prognostic in the entire PH population and in each of the PH groups 1 through 4. The REVEAL scores, when used as continuous prediction models, demonstrated the highest statistical prognostic power and granularity; the COMPERA 4-strata risk score provided subdifferentiation of the intermediate-risk group. Similar results were obtained when separately analyzing various subgroups (PH subgroups 1.1, 1.4.1, and 1.4.4; PH subgroups 3.1 and 3.2; group 2 with isolated postcapillary PH vs combined precapillary and postcapillary PH; patients of all groups with concomitant cardiac comorbidities; and severe [> 5 WU] vs nonsevere PH). INTERPRETATION: This comprehensive study with real-world data from 15 PH centers showed that PAH-designed risk scores possess predictive power in a large PH cohort, whether considered as common to the group or calculated separately for each PH group (1-4) and various subgroups.

Closed-cycle noble gas recycling system for high-repetition rate high-harmonic generation.

We present a compact closed-loop recycling system for noble and inert gases. It has been developed for an extreme-ultraviolet (XUV) frequency comb based on high-harmonic generation at 100 MHz repetition rate. The system collects gas injected at several bars of backing pressure through a micrometer-sized nozzle into the laser-interaction region with a differential pumping system comprising turbomolecular pumps, and subsequently compresses the gas to a pressure of up to 200 bar. By drastically reducing the waste of expensive gases such as xenon and krypton, it enables the long operation times needed for spectroscopic measurements, as well as for continuous operation of the XUV frequency comb.

Promising Directions: A Systematic Review of Psychosocial and Behavioral Interventions with Cultural Incorporation for Advanced and Metastatic Cancer.

BACKGROUND: Improving quality of life (QOL) in advanced and metastatic cancer is a priority with increasing survivorship. This systematic review synthesizes psychosocial and behavioral interventions incorporating culture with the goal of examining their benefit for understudied and medically underserved populations with advanced and metastatic cancer. METHOD: Reports were systematically screened for (1) a focus on advanced and metastatic cancer survivors, (2) psychosocial or behavioral intervention intended to improve QOL, (3) evidence of incorporating the culture(s) of understudied/underserved populations, and (4) availability in English. Bias was evaluated using the JBI Critical Appraisal Checklist and the Methodological index for non-randomized studies. Qualitative synthesis and quantitative meta-analyses were completed. RESULTS: Eighty-six reports containing 5981 participants' data were examined. Qualitative synthesis of 23 studies identified four overarching themes relevant for incorporating culture in interventions. Meta-analysis of 19 RCTs and 4 quasi-experimental studies containing considerable heterogeneity indicated greater improvements in QOL (g = 0.84), eudaimonic well-being (g = 0.53), distress (g = -0.49), and anxiety (g = -0.37) for main intervention conditions compared to controls. Meta-analysis of 10 single-arm trials containing minimal to moderate heterogeneity found benefit for anxiety (g = -0.54), physical symptoms (g = -0.39), and depression (g = -0.38). CONCLUSION: Psychosocial and behavioral interventions with cultural incorporation appear beneficial for improving QOL-related outcomes in advanced and metastatic cancer. Studies incorporating culture in psychosocial or behavioral interventions offer noteworthy insight and suggestions for future efforts such as attending to deep cultural structure.

Overexpression of REST Represses the Epithelial-Mesenchymal Transition Process and Decreases the Aggressiveness of Prostate Cancer Cells.

The RE-1 silencing transcription factor (REST) is a repressor factor related to neuroendocrine prostate cancer (PCa) (NEPC), a poor prognostic stage mainly associated with castration-resistant PCa (CRPC). NEPC is associated with cell transdifferentiation and the epithelial-mesenchymal transition (EMT) in cells undergoing androgen deprivation therapy (ADT) and enzalutamide (ENZ). The effect of REST overexpression in the 22rv1 cell line (xenograft-derived prostate cancer) on EMT, migration, invasion, and the viability for ENZ was evaluated. EMT genes, Twist and Zeb1, and the androgen receptor (AR) were evaluated through an RT-qPCR and Western blot in nuclear and cytosolic fractions of REST-overexpressing 22rv1 cells (22rv1-REST). The migratory and invasive capacities of 22rv1-REST cells were evaluated via Transwell® assays with and without Matrigel, respectively, and their viability for enzalutamide via MTT assays. The 22rv1-REST cells showed decreased nuclear levels of Twist, Zeb1, and AR, and a decreased migration and invasion and a lower viability for ENZ compared to the control. Results were expressed as the mean + SD of three independent experiments (Mann-Whitney U test, Kruskal-Wallis, Tukey test). REST behaves like a tumor suppressor, decreasing the aggressiveness of 22rv1 cells, probably through the repression of EMT and the neuroendocrine phenotype. Furthermore, REST could represent a response marker to ENZ in PCa patients.

Targeted Glycoproteomics Analysis Using MRM/PRM Approaches.

MS-target analyses are frequently utilized to analyze and validate structural changes of biomolecules across diverse fields of study such as proteomics, glycoproteomics, glycomics, lipidomics, and metabolomics. Targeted studies are commonly conducted using multiple reaction monitoring (MRM) and parallel reaction monitoring (PRM) techniques. A reliable glycoproteomics analysis in intricate biological matrices is possible with these techniques, which streamline the analytical workflow, lower background interference, and enhance selectivity and specificity.

Partial Cranial Reconstruction Using Titanium Mesh after Craniectomy: An Antiadhesive and Protective Barrier with Improved Aesthetic Outcomes.

OBJECTIVE: Describe a new, safe, technique that uses titanium mesh to partially cover skull defects immediately after decompressive craniectomy (DC). METHODS: This study is a retrospective review of 8 patients who underwent DC and placement of a titanium mesh. The mesh partially covered the defect and was placed between the temporalis muscle and the dura graft. The muscle was sutured to the mesh. All patients underwent cranioplasty at a later time. The study recorded and analyzed demographic information, time between surgeries, extra-axial fluid collections, postoperative infections, need for reoperation, cortical hemorrhages, and functional and aesthetic outcomes. RESULTS: After craniectomy, all patients underwent cranioplasty within an average of 112.5 days (30-240 days). One patient reported temporalis muscle atrophy, which was the only complication observed. During the cranioplasties, no adhesions were found between temporalis muscle, titanium mesh, and underlying dura. None of the patients showed complications in the follow-up computerized tomography scans. All patients had favorable aesthetic and functional results. CONCLUSIONS: Placing a titanium mesh as an extra step during DC could have antiadhesive and protective properties, facilitating subsequent cranioplasty by preventing adhesions and providing a clear surgical plane between the temporalis muscle and intracranial tissues. This technique also helps preserve the temporalis muscle and enhances functional and aesthetic outcomes postcranioplasty. Therefore, it represents a safe alternative to other synthetic anti-adhesive materials. Further studies are necessary to draw definitive conclusions and elucidate long-term outcomes, however, the results obtained hold great promise for the safety and efficacy of this technique.

Using PAH-SYMPACT to assess quality of life in patients with pulmonary hypertension associated with chronic lung disease.

Chronic lung disease (CLD) is the second leading cause of pulmonary hypertension (PH) and is associated with significant morbidity and mortality. Although PH associated with CLD (PH-CLD) leads to impaired health-related quality of life (HRQOL), there are no validated tools to assess HRQOL in PH-CLD. The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT) is an HRQOL instrument aimed at assessing the symptoms and impact of PH on overall function and well-being. We performed a single-center prospective cohort study using PAH-SYMPACT scores to compare symptoms, exercise capacity and HRQOL in patients with PAH and PH-CLD. One hundred and twenty-five patients (99 patients with idiopathic/heritable PAH and 26 with PH-CLD) completed the PAH-SYMPACT questionnaire which consists of 22 questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive/emotional (CE) impact. Higher scores indicate worse HRQOL. We compared patients with PAH and PH-CLD using a Wilcoxon rank sum or chi-squared test as appropriate. Multivariate linear regression analysis was used to assess the relationship between PH classification and SYMPACT scores. Compared to PAH, patients with PH-CLD were older, more likely to use oxygen and had worse functional class and exercise capacity. While there was no significant difference between the two groups in CP, CV, or CE domain scores, patients with PH-CLD had significantly worse PI scores by univariate (1.79 vs. 1.13, p < 0.001) and multivariate analysis (1.61 vs. 1.17, p = 0.02) and overall worse SYMPACT scores (1.19 vs. 0.91, p = 0.03). In conclusion, patients with PH-CLD have worse HRQOL as assessed by the PAH-SYMPACT questionnaire versus patients with PAH. Although PAH-SYMPACT has not been validated in PH-CLD, the results of this study can guide clinicians in understanding the symptoms and impact of PH-CLD relative to PAH.

Changes in vascular function and correlation with cardiotoxicity in women with newly diagnosed breast cancer undergoing HER2-directed therapy with and without anthracycline/cyclophosphamide.

Aims: The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk. Methods and results: Single-centre, prospective cohort study of women with newly diagnosed stage 1-3 HER2-positive breast cancer undergoing HER2-Tx +/- AC. All participants underwent baseline and 3-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers [C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1ß)], and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of >10% to a value <53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperaemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs. 22%; P = 0.003). A decrease in CNP and log NRG-1ß levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs. 7.4%; P = 0.20 and NRG-1ß: 15% vs. 11%; P = 0.69) nor did GLS (35% vs. 37%; P = 0.89). Patients treated with AC had a significantly lower 3D LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3% (SD 3) vs. 63.8% (SD 4); P = 0.02). Reactive hyperaemia index and GLS were the only parameters correlating with LVEF change. Conclusion: Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.

Trajectories of Opioid Misuse and Opioid Use Disorder Among Adults With Chronic Pain and HIV: An Observational Study.

OBJECTIVES: In a longitudinal cohort of patients with HIV and chronic pain, we sought to (1) identify trajectories of opioid misuse and opioid use disorder (OUD) symptoms, and to (2) determine whether prescription opioid dose was associated with symptom trajectories. METHODS: We leveraged an existing 12-month longitudinal observational study, Project PIMENTO, of persons living with HIV and chronic pain who received care at a hospital system in the Bronx, New York. A quota sampling strategy was used to ensure variability of prescribed opioid use in the recruited sample. Research interviews occurred quarterly and assessed opioid behaviors and criteria for OUD. To describe symptom trajectories, we conducted 2 separate longitudinal latent class analyses to group participants into (1) opioid misuse and (2) OUD trajectories. Finally, we used multinomial logistic regression models to examine the relationship between baseline prescription opioid dose and symptom trajectories. RESULTS: Of 148 total participants, at baseline 63 (42.6%) had an active opioid prescription, 69 (46.6%) met the criteria for current opioid misuse, and 44 (29.7%) met the criteria for current OUD. We found 3 opioid misuse and 3 OUD symptom trajectories, none of which showed worsened symptoms over time. In addition, we found that higher prescription opioid dose at baseline was associated with a greater OUD symptom trajectory. CONCLUSIONS: Opioid misuse and OUD were common but stable or decreasing over time. Although these results are reassuring, our findings also support prior studies that high-dose opioid therapy is associated with greater OUD symptoms.

Complications of Right Heart Catheterization in Patients ≥70 Years of Age With Suspected Pulmonary Hypertension: Experience From a Tertiary Care Center.

Right heart catheterization (RHC) represents the gold standard diagnostic approach for pulmonary hypertension (PH). Historically, the complication rates of RHC are known to be low. The study aimed to evaluate the indications for performing RHC and the occurrence of adverse events related to the procedure in patients > over 70 years of age in a Mexican Tertiary Care Center. We conducted a retrospective single-center registry from July 2017 to July 2022. A total of 517 patients with suspected PH underwent RHC. The cohort included patients <70 (n = 427) and ≥70 years of age (n = 90). Adverse events were classified as major (eg, death, pneumothorax, and carotid artery puncture) and minor (eg, atrial arrhythmia, superior vena cava dissection, incidental arterial puncture, and local hematoma). Appropriate hemodynamic parameters were recorded. No report of major adverse events in the entire cohort. In the <70 years age group, 9 minor events, and 3 minor events were in the ≥70-year-old patients (P < 0.0001). There was a significant difference in the measurement of mean pulmonary artery pressure (mPAP) between the <70 years old vs ≥70 years old (P < 0.001); there was a significant difference in right atrial pressures: 4.71 ± 3.14 mmHg in the <70-year-old vs 4.07 ± 1.94 mmHg for the ≥ 70-year-old group (P = 0.014). Our findings suggest that RHC can be safely performed in patients aged ≥70 years using different vascular access routes without significant major complications.