Understanding variability: the role of meta-analysis of variance.

Meta-analyses traditionally compare the difference in means between groups for one or more outcomes of interest. However, they do not compare the spread of data (variability), which could mean that important effects and/or subgroups are missed. To address this, methods to compare variability meta-analytically have recently been developed, making it timely to review them and consider their strengths, weaknesses, and implementation. Using published data from trials in major depression, we demonstrate how the spread of data can impact both overall effect size and the frequency of extreme observations within studies, with potentially important implications for conclusions of meta-analyses, such as the clinical significance of findings. We then describe two methods for assessing group differences in variability meta-analytically: the variance ratio (VR) and coefficient of variation ratio (CVR). We consider the reporting and interpretation of these measures and how they differ from the assessment of heterogeneity between studies. We propose general benchmarks as a guideline for interpreting VR and CVR effects as small, medium, or large. Finally, we discuss some important limitations and practical considerations of VR and CVR and consider the value of integrating variability measures into meta-analyses.

Imaging Findings Associated with Failure of Conservative Management after Blunt Extraperitoneal Bladder Injury.

OBJECTIVES: To identify risk factors for failure of conservative management (CM) for uncomplicated extraperitoneal bladder injuries (EBI). METHODS: The trauma registry at a single Level 1 trauma center was queried for patients presenting with a blunt EBI between 2004 and 2022. Patients with CM and follow-up through at least one postoperative cystogram or catheter removal were included. A univariable analysis for associations with a composite outcome of either persistent leakage or delayed cystorrhaphy was completed. RESULTS: Eighty-four patients with an EBI underwent CM. Seventy-eight (93%) patients had an associated pelvic fracture and 17 of 84 (20%) underwent embolization for pelvic hemorrhage. Thirty-four (41%) patients also had delayed phase imaging, 17 (20%) of whom had extravasation from their bladder on delays. Six (7%) patients failed initial CM. There was no association between the composite outcome and pelvic fracture (p=0.35) or embolization (p=0.41). American Association for the Surgery of Trauma (AAST) grade 5 injuries (p=0.01) and the presence of extravasation on delayed-phase Computed Tomography (p=0.03) were associated with the composite outcome. CONCLUSIONS: Contrast extravasation on initial delayed-phase imaging despite urethral catheter drainage and AAST injury grade were associated with failed CM after EBI. This may reflect injuries that mechanistically yield incomplete antegrade drainage with CM.

Tumor lysate particle only vaccine (TLPO) vs. Tumor lysate particle-loaded, dendritic cell vaccine (TLPLDC) to prevent recurrence in resected stage III/IV melanoma patients: Results of a phase I/IIa trial.

BACKGROUND: The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from dendritic cells (DC) loaded ex vivo with autologous tumor lysate (TL). TLPLDC has been shown to decrease recurrence in resected Stage III/IV melanoma patients in a Phase IIb trial. The TL particle only (TLPO) vaccine is produced by loading of yeast cell wall particles with autologous TL and direct injection allowing for in vivo DC loading. We have compared the TLPO and TLPLDC vaccines in an embedded Phase I/IIa trial of a larger Phase IIb trial of the TLPLDC vaccine. METHODS: Patients rendered clinically disease-free after surgery were randomized 2:1 to receive the TLPO or TLPLDC vaccine and followed for recurrence and death. Patients had scheduled intradermal inoculations at 0, 1, 2, 6, 12, and 18 months after enrollment. Kaplan-Meier and log-rank analysis were used to compare disease-free survival (DFS) and overall survival (OS) in an intention-to-treat (ITT) analysis. RESULTS: Sixty-three patients were randomized, 43 TLPO and 20 TLPLDC. Patients randomized to the TLPO arm were more likely to be female (37.2% vs. 10.0 %, p = 0.026), but otherwise no significant clinicopathological differences were identified. No differences in related adverse events (AE) were found between treatment arms. At a median follow-up of 20.5 months, the DFS (60.8% vs. 58.7 %, p = 0.714) and OS (94.6% vs. 93.8 %, p = 0.966) were equivalent between the TLPO and TLPLDC groups, respectively. No statistical differences were found in subgroup analyses between vaccine types, which accounted for receipt of immunotherapy and the use of G-CSF pre-blood draw. CONCLUSIONS: In a randomized, double-blind Phase I/IIa trial, there were no differences in DFS or OS in resected Stage III/IV melanoma patients receiving adjuvant TLPO versus TLPLDC vaccines. Given manufacturing advantages, further efficacy testing of TLPO is warranted in a Phase III trial.

Changes in participatory and societal outcomes during the waiting period for cochlear implantation - an observational study.

INTRODUCTION: Various factors, including an aging population and expanding eligibility criteria, may increase the demand for cochlear implants (CIs), potentially resulting in longer waiting times. In most Dutch CI centers, the time between referral and surgery exceeds 6 months. Clinical experience suggests that during the waiting period for cochlear implantation, hearing and communication difficulties increase. Simultaneously, there is an interest in outcomes more closely aligned with patient values and needs, which resulted in the SMILE (Societal Merit of Interventions on hearing Loss Evaluation) study. This paper presents results on observed changes in societal and participatory outcomes during waiting time in participants with a time to CI surgery exceeding 6 months. METHODS: SMILE is a prospective multi-center study including 232 individuals who were referred for unilateral CI. Continuous and nominal data from multiple questionnaires, sent immediately after referral and shortly before surgery, were analyzed by computing differences, Cohen's D, and odds ratios. RESULTS: Of the total 232 participants, 102 had a time between inclusion and surgery exceeding 6 months. Of these, 89 had (partially) filled out surveys at both time points. Of all the domain scores 55% did not show differences between timepoints. All Cohen's D estimates were relatively small, ranging from - 0.298 to 0.388 for those outcomes that showed noteworthy changes. CONCLUSION: Waiting time from referral to surgery, even though exceeding 6 months, was observed to not seriously affect non-clinically-prioritized patients in an adverse way. Future investigations should identify subgroups on tolerable waiting times regarding short- and long-term outcomes. TRIAL REGISTRATION: Trial registration number at ClinicalTrials.gov: NCT05525221, 25-8-2022.

USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.

Mammalian DNA replication relies on various DNA helicase and nuclease activities to ensure accurate genetic duplication, but how different helicase and nuclease activities are properly directed remains unclear. Here, we identify the ubiquitin-specific protease, USP50, as a chromatin-associated protein required to promote ongoing replication, fork restart, telomere maintenance, cellular survival following hydroxyurea or pyridostatin treatment, and suppression of DNA breaks near GC-rich sequences. We find that USP50 supports proper WRN-FEN1 localisation at or near stalled replication forks. Nascent DNA in cells lacking USP50 shows increased association of the DNA2 nuclease and RECQL4 and RECQL5 helicases and replication defects in cells lacking USP50, or FEN1 are driven by these proteins. Consequently, suppression of DNA2 or RECQL4/5 improves USP50-depleted cell resistance to agents inducing replicative stress and restores telomere stability. These data define an unexpected regulatory protein that promotes the balance of helicase and nuclease use at ongoing and stalled replication forks.

A randomized, placebo-controlled trial of purified anthocyanins on cognitive function in individuals at elevated risk for dementia: Analysis of inflammatory biomarkers toward personalized interventions.

BACKGROUND: Dementia poses a significant global health challenge. Anthocyanins neutralize free radicals, modulate signaling pathways, inhibit pro-inflammatory genes, and suppress cytokine production and may thus have positive cognitive effects in people at increased risk of dementia. We aim to investigate the effects of purified anthocyanins on cognitive function in people at increased risk of dementia according to their inflammation status based on blood-based inflammatory biomarkers. METHODS: This is a secondary analysis of a 24-week randomized, double-blind, placebo-controlled trial. Cluster analysis was performed to categorize two groups based on their individual inflammatory biomarker profile using multiplex sandwich ELISA for the quantitative measurement of cytokines. Descriptive statistics and longitudinal models assessed cognitive outcomes. The primary comparison was the group difference at week 24 based on a modified intention-to-treat analysis. RESULTS: Cluster analysis revealed two distinct inflammatory biomarker profiles. In Cluster 1 (high levels of inflammation biomarkers), anthocyanin treatment showed a statistically significant improvement on cognitive function compared to placebo at 24 weeks. No significant differences were observed in Cluster 2 (low levels of inflammation biomarkers). The demographic characteristics, cognitive scores, and biomarker distributions were similar between treatment groups at baseline. However, cluster 1 exhibited higher BMI, diabetes prevalence, medication usage, and lower HDL cholesterol levels. CONCLUSION: Individuals with elevated levels of inflammation markers benefited from anthocyanin treatment to enhance cognitive performance, whereas those with lower levels did not. The anti-inflammatory and antioxidant properties of anthocyanins make them a promising intervention, and future prospective trials in people with increased inflammation are warranted.

The number of fundamental constants from a spacetime-based perspective.

We revisit Duff, Okun, and Veneziano's divergent views on the number of fundamental constants and argue that the issue can be set to rest by having spacetime as the starting point. This procedure disentangles the resolution in what depends on the assumed spacetime (whether relativistic or not) from the theories built over it. By defining that the number of fundamental constants equals the minimal number of independent standards necessary to express all observables, as assumed by Duff, Okun, and Veneziano, it is shown that the same units fixed by the apparatuses used to construct the spacetimes are enough to express all observables of the physical laws defined over them. As a result, the number of fundamental constants equals one in relativistic spacetimes.

Decorin, an exercise-induced secretory protein, is associated with improved prognosis in breast cancer patients but does not mediate anti-tumorigenic tissue crosstalk in mice.

BACKGROUND: Regular exercise can reduce incidence and progression of breast cancer, but the mechanisms for such effects are not fully understood. METHODS: We used a variety of rodent and human experimental model systems to determine whether exercise training can reduce tumor burden in breast cancer and to identify mechanism associated with any exercise training effects on tumor burden. RESULTS: We show that voluntary wheel running slows tumor development in the mammary specific polyomavirus middle T antigen overexpression (MMTV-PyMT) mouse model of breast cancer but only when mice are not housed alone. We identify the proteoglycan decorin as a contraction-induced secretory factor that systemically increases in patients with breast cancer immediately following exercise. Moreover, high expression of decorin in tumors is associated with improved prognosis in patients, while treatment of breast cancer cells in vitro with decorin reduces cell proliferation. Notwithstanding, when we overexpressed decorin in murine muscle or injected recombinant decorin systemically into mouse models of breast cancer, elevated plasma decorin concentrations did not result in higher tumor decorin levels and tumor burden was not improved. CONCLUSION: Exercise training is anti-tumorigenic in a mouse model of luminal breast cancer, but the effect is abrogated by social isolation. The proteoglycan decorin is an exercise-induced secretory protein, and tumor decorin levels are positively associated with improved prognosis in patients. The hypothesis that elevated plasma decorin is a mechanism by which exercise training improves breast cancer progression in humans is not, however, supported by our pre-clinical data since elevated circulating decorin did not increase tumor decorin levels in these models.

Monotherapy or combination therapy in PsA: current aspects.

Psoriatic arthritis (PsA) is an immune-mediated inflammatory disease with heterogeneity regarding its clinical features, mainly affecting the skin and the musculoskeletal system; additionally, extra-musculoskeletal manifestations and comorbidities are common, adding complexity to its treatment. In the last decades, a plethora of therapeutic options have been available, including conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs), biological DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), and many recommendations have been published regarding the proper use of them in patients with PsA. In rheumatoid arthritis, the combination of conventional with bDMARDs or tsDMARDs is a common and recommended practice, whereas in PsA there is scarce data about the benefit of this combination. This review summarizes all the available data from randomized clinical trials, observational studies, and registries about the value of this therapeutic strategy.

Use of b/tsDMARDs in PsA: with or without csDMARDs Over the last years, many different b/ts DMARDs have been porven to be efficacious in psoriatic arthritis (PsA). Although in rheumatoid arthritis, it is established that most of these drugs work better in combination with conventional synthetic DMARDs (e.g methotrexate), this seems to be slightly different in PsA. Herein, we review the current literature about the combination therapy versus monotherapy of b/ts DMARDs in PsA. We present the results of this narrative review in a structured (per drug category) way, so that it is easier for the reader to find relevant information. There is no doubt that the currently available treatment options in PsA have changed the course of the disease and improved the functional status of the patients. However, as there is still a substantial proportion of patients who do not achieve remission or low disease activity, the need to find effective therapeutic regimens or follow different strategies is growing. In this direction, the combination of a conventional synthetic with biological or targeted synthetic DMARD does not seem to be more effective than the monotherapy of the latter. This seems to be more pronounced in the newer drug categories (anti-IL-17, anti-IL23 and JAKi) compared to the TNFi, where the co-administration of a csDMARD improves their survival.

Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

Dissecting the oncogenic mechanisms of POT1 cancer mutations through deep scanning mutagenesis.

Mutations in the shelterin protein POT1 are associated with diverse cancers, but their role in cancer progression remains unclear. To resolve this, we performed deep scanning mutagenesis in POT1 locally haploid human stem cells to assess the impact of POT1 variants on cellular viability and cancer-associated telomeric phenotypes. Though POT1 is essential, frame-shift mutants are rescued by chemical ATR inhibition, indicating that POT1 is not required for telomere replication or lagging strand synthesis. In contrast, a substantial fraction of clinically-validated pathogenic mutations support normal cellular proliferation, but still drive ATR-dependent telomeric DNA damage signaling and ATR-independent telomere elongation. Moreover, this class of cancer-associated POT1 variants elongates telomeres more rapidly than POT1 frame-shifts, indicating they actively drive oncogenesis and are not simple loss-of-function mutations.

The electronic artificial urinary sphincter: ongoing innovation of a classic device-a narrative review.

Background and Objective: While the modern artificial urinary sphincter (AUS) has benefited from incremental innovation, which has improved both device efficacy and complication rates, the foundational technology in use in Boston Scientific's AMS800 can be traced back to the fundamental hydraulic tenets of the AS721. Research and development in adaptive technology and electronic integration stand to further improve AUS outcomes. Methods: The Medline online retrieval system was queried using the MeSH terms "artificial urinary sphincter", "electronic", "complications", "history", and "development" in various combinations. Publications were reviewed if applicable, and their reference lists were used to collect additional articles as needed. Final article inclusion was based on senior author discretion. Key Content and Findings: The AMS800 AUS is the gold standard for male stress incontinence implants. A 2015 consensus conference set out the goals for sphincter device development in the coming decades. A future ideal sphincter would adjust cuff pressure dynamically as well as function with minimal manipulation, or even via electronic control. Multiple new devices are in various states of development. During the next decade, artificial urinary sphincter technology is likely to include multiple Food and Drug Administration (FDA)-approved devices with varying features aimed at satisfying the 2015 consensus conference goal for an "ideal" AUS. Conclusions: The future of stress incontinence therapy lies in both continued innovation for the AUS, as well as advances in regenerative medicine. Electronic and adaptive developments in AUS technology will increase device safety, efficacy, and longevity while improving the user and caregiver experience. For some, regenerative medicine may even make AUS technology obsolete.

Assessing the reporting quality of pediatric neuro-oncology protocols, abstracts, and trials: Adherence to the SPIRIT and CONSORT statements.

Background: It is of vital importance to comprehensively and transparently report clinical trial activity. The SPIRIT 2013 and CONSORT 2010 statements exist to define items to be reported in clinical trial protocols and randomized controlled trials, respectively. The aim of this methodological review was to assess the reporting quality of pediatric neuro-oncology trial protocols and trial result articles. Methods: Published trial protocols and phase II/III trial result articles relating to pediatric brain tumors (published after the introduction of the SPIRIT 2013 statement), were identified through searches of 4 electronic bibliographic databases. The reporting quality of included trial protocols and result articles was assessed against the aforementioned statements. In addition, the CONSORT-A checklist was used to assess the abstracts of trial result articles. Percentage adherence was calculated for each article. Results: Nine trial protocols, 68 phase II trials, and 8 phase III trial result articles were included. Mean adherence of trial protocols to the SPIRIT statement was 76.8% (SD: 0.09). Mean adherence of trial abstracts to CONSORT-A was 67.4% (SD: 0.13) for phase II abstracts and 47.5% (SD: 0.09) for phase III abstracts. Adherence of trial result articles to CONSORT was 71.3% (SD: 0.10) for phase II trials and 70.3% (SD: 0.13) for phase III trials. Conclusions: The reporting quality of pediatric neuro-oncology trial protocols and trial result articles requires improvement, particularly in the areas of randomization and blinding. This is consistent with our previously published findings following similar assessment of reporting quality for adult neuro-oncology trial protocols and result articles.

On the Nature of the Last Common Ancestor: A Story from its Translation Machinery.

The Last Common Ancestor (LCA) is understood as a hypothetical population of organisms from which all extant living creatures are thought to have descended. Its biology and environment have been and continue to be the subject of discussions within the scientific community. Since the first bacterial genomes were obtained, multiple attempts to reconstruct the genetic content of the LCA have been made. In this review, we compare 10 of the most extensive reconstructions of the gene content possessed by the LCA as they relate to aspects of the translation machinery. Although each reconstruction has its own methodological biases and many disagree in the metabolic nature of the LCA all, to some extent, indicate that several components of the translation machinery are among the most conserved genetic elements. The datasets from each reconstruction clearly show that the LCA already had a largely complete translational system with a genetic code already in place and therefore was not a progenote. Among these features several ribosomal proteins, transcription factors like IF2, EF-G, and EF-Tu and both class I and class II aminoacyl tRNA synthetases were found in essentially all reconstructions. Due to the limitations of the various methodologies, some features such as the occurrence of rRNA posttranscriptional modified bases are not fully addressed. However, conserved as it is, non-universal ribosomal features found in various reconstructions indicate that LCA's translation machinery was still evolving, thereby acquiring the domain specific features in the process. Although progenotes from the pre-LCA likely no longer exist recent results obtained by unraveling the early history of the ribosome and other genetic processes can provide insight to the nature of the pre-LCA world.

Divergent sensory pathways of sneezing and coughing.

Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3-) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST+]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.

Surgical outcomes and risk factors for overall mortality in brain arteriovenous malformations patients: a retrospective analysis.

Background: Brain arteriovenous malformations (AVMs) are challenging vascular lesions. Extensive follow-up studies are necessary to refine the therapeutic algorithm, and to improve long-term survival in these patients. The aim of the study was to assess surgical outcomes, and to evaluate overall long-term mortality in patients treated for brain AVMs. Methods: This retrospective single-center study included 191 patients with brain AVMs, admitted between 2012 and 2022. Clinical and angiographical particularities have been analyzed, to identify factors that might influence early outcome and overall long-term mortality. Results: Out of 79 patients undergoing surgery, 51 had ruptured AVMs with total resection achieved in 68 cases (86.1%). Deep venous drainage was associated with incomplete resection. Female sex, admission modified Rankin Scale (mRS) > 2, and eloquent location were independent predictors of poor outcomes. Multiple venous drainage was associated with a higher risk of worsened early outcome. Eloquent brain region involvement, conservative treatment, increasing age, admission mRS > 2, and comorbidities significantly decrease survival in brain AVM patients. Patients treated with interventional treatments had significantly better survival than the conservatively managed ones, when adjusting for age and admission mRS. Conclusion: The study identified female sex, poor neurologic status on admission and eloquence as independent prognostic factors for a negative outcome after surgery. Patients who received interventional treatment had significantly better survival than patients managed conservatively. We recommend employing tailored, proactive management strategies as they significantly enhance long-term survival in brain AVM patients.

Investigation of hydrochemical characteristic, water quality and associated health risks of metals and metalloids in water resources in the vicinity of Akamkpa quarry district, southeastern, Nigeria.

Quarrying of rock aggregates generates produced water that, if not handled properly will be a source of pollution for nearby water bodies, thus affecting the chemistry of the water. This study examined the chemistry, impact of quarrying activities on water resources and the health consequences/risks posed by ingestion of the water by humans in the Akamkpa quarry region in southeastern Nigeria. Thirty (30) water samples consisting of pond water, stream water, hand dug wells, and borehole samples were collected and analyzed for their physicochemical parameters using standard methods. The results obtained from the analyses indicated that the water was moderately acidic, fresh, and not salty, with many parameters below the recommended standards with Ca2+, and HCO3- being the dominant ions present in the water resources. Rock weathering processes including silicate weathering as illustrated by hydrochemical facies, cross plots, and Gibbs diagrams are the dominant mechanisms influencing the quality and major ions chemistry of the water resources with minor contributions from dissolution, anthropogenic activities, and ion exchange. Ca-Mg-SO4-Cl and Na-K-HCO3- are the most important water types. Although the water quality index shows that the water is suitable for human use and irrigation, the mean values of As, Cd, Pb, and Se are above the acceptable limits. Additionally, the calculated contamination factor revealed the water resources are moderate to highly contaminated by As, Cd, Cr, Mo, Pb, Sb, and Se, and are therefore unsuitable for consumption with regards to these parameters. However, the residual sodium carbonate and water hazard index (WHI) values showed that 38% to 90% of sites in the quarry area were unsuitable for cultivation, 10-30% were in the low to medium impact category, and 60% were classified as risky and are from high to very high impact category. A non-cancer study of inhabitants living in the vicinity of the quarry area indicated that 6.7% of the sites have values greater than one, indicating that it may endanger the health of the people. Therefore, constant monitoring of the water quality is recommended as long-term use of contaminated water can harm humans, plants, and soils.

Associations between Post-Intensive Care Syndrome Domains in Cardiac Arrest Survivors and Their Families One Month Post-Event.

Background: Post-intensive care syndrome (PICS) affects many critical care survivors and family members. Nevertheless, the relationship between PICS-relevant domains in cardiac arrest (CA) survivors and psychological distress in their family members (henceforth, PICS-F) remains underexplored. Methods: We enrolled consecutive CA patients admitted between 16 August 2021 and 28 June 2023 to an academic medical center, along with their close family members, in prospective studies. Survivors' PICS domains were: physical dependence (Physical Self-Maintenance Scale, PSMS), cognitive impairments (Modified Telephone Interview for Cognitive Status, TICS-M), and post-traumatic stress disorder (PTSS) symptoms (PTSD Checklist-PCL 5), as well as PICS-F (PCL-5 Total Score). Hierarchical multivariate linear regressions examined associations between PICS-F and survivors' PICS domains. Results: Of 74 dyads (n = 148), survivors had a mean (SD) age of 56 ± 16 years, with 61% being male and with a median hospital stay of 28 days. Family members (43% spouses) were slightly younger (52 ± 14 years), predominantly female (72%), and of minority race/ethnicity (62%). A high prevalence of PICS assessed 28.5 days (interquartile range 10-63) post-CA was observed in survivors (78% physical dependence, 54% cognitive impairment, 30% PTSS) and in family members (30% PTSS). Survivor PTSS was significantly associated with family member distress (ß = 0.3, p = 0.02), independent of physical dependence (ß = 0.0, p = 0.9), cognitive impairment (ß = -0.1, p = 0.5), family member characteristics, and duration of hospitalization. Conclusions: Both CA survivors and their family members showed substantial evidence of likely PICS. Survivor PTSS is notably associated with family member distress, highlighting the need for dyadic interventions to enhance psychosocial outcomes.