Hypoxia-Preconditioned BMSC-Derived Exosomes Induce Mitophagy via the BNIP3-ANAX2 Axis to Alleviate Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence-related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich extracellular vesicles to NPCs, thereby alleviating aging-associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane-bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2-TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia-induced BMSC exosomes deliver BNIP3-rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

Emergent bilingual children during the silent period: A scoping review of their communication strategies and classroom environments.

This scoping review aimed to investigate the communication strategies utilized by children who acquire a minority language (L1) and subsequently learn a community language (L2) during what is commonly referred to as the "silent period." Electronic database searches were conducted using keywords such as "silent period" and "bilingual children," resulting in the inclusion of 40 studies in the review. The findings revealed that emergent bilingual children utilize various communication strategies, including nonverbal communication, private speech, and their L1, to communicate within classroom environments. The findings shed light on the adaptability of emergent bilingual children during early stage of L2 acquisition. Furthermore, our review provides information about the classroom contexts such as teacher support and peer interactions where children develop their L2 skills. From a clinical perspective, recognizing these strategies and classroom contexts could significantly enhance the screening process for emergent bilingual children.

Surgeon Performance as a Predictor for Patient-Reported Outcomes After Arthroscopic Partial Meniscectomy.

Background: Surgeon performance has been investigated as a factor affecting patient outcomes after orthopaedic procedures to improve transparency between patients and providers. Purpose/Hypothesis: The purpose of this study was to identify whether surgeon performance influenced patient-reported outcomes (PROMs) 1 year after arthroscopic partial meniscectomy (APM). It was hypothesized that there would be no significant difference in PROMs between patients who underwent APM from various surgeons. Study Design: Case-control study; Level of evidence, 3. Methods: A prospective cohort of 794 patients who underwent APM between 2018 and 2019 were included in the analysis. A total of 34 surgeons from a large multicenter health care center were included. Three multivariable models were built to determine whether the surgeon-among demographic and meniscal pathology factors-was a significant variable for predicting the Knee injury and Osteoarthritis Outcome Score (KOOS)-Pain subscale, the Patient Acceptable Symptom State (PASS), and a 10-point improvement in the KOOS-Pain at 1 year after APM. Likelihood ratio (LR) tests were used to determine the significance of the surgeon variable in the models. Results: The 794 patients were identified from the multicenter hospital system. The baseline KOOS-Pain score was a significant predictor of outcome in the 1-year KOOS-Pain model (odds ratio [OR], 2.1 [95% CI, 1.77-2.48]; P < .001), the KOOS-Pain 10-point improvement model (OR, 0.57 [95% CI, 0.44-0.73), and the 1-year PASS model (OR, 1.42 [95% CI, 1.15-1.76]; P = .002) among articular cartilage pathology (bipolar medial cartilage) and patient-factor variables, including body mass index, Veterans RAND 12-Item Health Survey-Mental Component Score, and Area Deprivation Index. The individual surgeon significantly impacted outcomes in the 1-year KOOS-Pain mixed model in the LR test (P = .004). Conclusion: Patient factors and characteristics are better predictors for patient outcomes 1 year after APM than surgeon characteristics, specifically baseline KOOS-Pain, although an individual surgeon influenced the 1-Year KOOS-Pain mixed model in the LR test. This finding has key clinical implications; surgeons who wish to improve patient outcomes after APM should focus on improving patient selection rather than improving the surgical technique. Future research is needed to determine whether surgeon variability has an impact on longer-term patient outcomes.

Mitochondrial-Targeted Metal-Phenolic Nanoparticles to Attenuate Intervertebral Disc Degeneration: Alleviating Oxidative Stress and Mitochondrial Dysfunction.

As intervertebral disc degeneration (IVDD) proceeds, the dysfunctional mitochondria disrupt the viability of nucleus pulposus cells, initiating the degradation of the extracellular matrix. To date, there is a lack of effective therapies targeting the mitochondria of nucleus pulposus cells. Here, we synthesized polygallic acid-manganese (PGA-Mn) nanoparticles via self-assembly polymerization of gallic acid in an aqueous medium and introduced a mitochondrial targeting peptide (TP04) onto the nanoparticles using a Schiff base linkage, resulting in PGA-Mn-TP04 nanoparticles. With a size smaller than 50 nm, PGA-Mn-TP04 possesses pH-buffering capacity, avoiding lysosomal confinement and selectively accumulating within mitochondria through electrostatic interactions. The rapid electron exchange between manganese ions and gallic acid enhances the redox capability of PGA-Mn-TP04, effectively reducing mitochondrial damage caused by mitochondrial reactive oxygen species. Moreover, PGA-Mn-TP04 restores mitochondrial function by facilitating the fusion of mitochondria and minimizing their fission, thereby sustaining the vitality of nucleus pulposus cells. In the rat IVDD model, PGA-Mn-TP04 maintained intervertebral disc height and nucleus pulposus tissue hydration. It offers a nonoperative treatment approach for IVDD and other skeletal muscle diseases resulting from mitochondrial dysfunction, presenting an alternative to traditional surgical interventions.

Preoperative Synovial Tissue and Synovial Fluid Biomarkers as Predictors for Outcomes After Knee Arthroscopy and ACL Reconstruction: A Narrative Review.

Background: Biomarkers collected in synovial tissue and fluid have been identified as potential predictors of outcomes after arthroscopy. Purpose: To provide a narrative review of the current literature that assesses the associations between preoperative biomarkers in the synovial fluid or synovial tissue and patient outcomes after knee arthroscopy. Study Design: Narrative review. Methods: We searched the PubMed database with keywords, "biomarkers AND arthroscopy," "biomarkers AND anterior cruciate ligament reconstruction," and "biomarkers AND meniscectomy." To be included, studies must have collected synovial fluid or synovial tissue from patients before or during arthroscopic knee surgery and analyzed the relationship of biomarkers to postoperative patient outcomes. Biomarkers were classified into 4 main categories: metabolism of aggrecan in cartilage, metabolism of collagen in cartilage (type II collagen), noncollagenous proteins in the knee, and other. When biomarker levels and outcomes were expressed with continuous variables, we abstracted the Pearson or Spearman correlation coefficients as the effect measure. If the biomarker values were continuous and the outcomes binary, we abstracted the mean or median biomarker values in those with favorable versus unfavorable outcomes. We calculated effect sizes as the difference between means of both groups divided by the standard deviation from the mean in the group with better outcomes. Results: Eight studies were included in the review. Each study reported different patient outcomes. Biomarkers associated with metabolism of aggrecan, type II collagen metabolism, and noncollagenous proteins as well as inflammatory biomarkers had statistically significant associations with a range of patient outcomes after knee arthroscopy. Difference across studies in sample size and outcome measures precluded choosing a single biomarker that best predicted patient outcomes. Conclusion: The findings suggest that biomarkers associated with metabolism of aggrecan, type II collagen metabolism, noncollagenous proteins, as well as inflammatory biomarkers may help surgeons and their patients anticipate surgical outcomes.

Now it's your turn!: Eye blink rate in a Jenga task modulated by interaction of task wait times, effortful control, and internalizing behaviors.

Dopamine is a versatile neurotransmitter with implications in many domains, including anxiety and effortful control. Where high levels of effortful control are often regarded as adaptive, other work suggests that high levels of effortful control may be a risk factor for anxiety. Dopamine signaling may be key in understanding these relations. Eye blink rate is a non-invasive proxy metric of midbrain dopamine activity. However, much work with eye blink rate has been constrained to screen-based tasks which lack in ecological validity. We tested whether changes in eye blink rate during a naturalistic effortful control task differ as a function of parent-reported effortful control and internalizing behaviors. Children played a Jenga-like game with an experimenter, but for each trial the experimenter took an increasingly long time to take their turn. Blinks-per-second were computed during each wait period. Multilevel modeling examined the relation between duration of wait period, effortful control, and internalizing behaviors on eye blink rate. We found a significant 3-way interaction between effortful control, internalizing behaviors, and duration of the wait period. Probing this interaction revealed that for children with low reported internalizing behaviors (-1 SD) and high reported effortful control (+1 SD), eye blink rate significantly decreased as they waited longer to take their turn. These findings index task-related changes in midbrain dopamine activity in relation to naturalistic task demands, and that these changes may vary as a function of individual differences in effortful control and internalizing behaviors. We discuss possible top-down mechanisms that may underlie these differences.

Patients with advanced cancer and their spouses parenting minor children: The role of the relationship context in parenting concerns.

OBJECTIVE: Patients with advanced cancer who parent minor children report parenting concerns and increased psychological distress. This cross-sectional study seeks to understand parenting-related issues in patients and spousal caregivers from a relationship perspective. METHODS: Patients with a metastatic solid malignancy and their spouses independently completed cross-sectional assessments of psychological distress (Hospital Anxiety and Depression Scale), parenting concerns (Parenting Concern Questionnaire) and efficacy (Cancer-Related Parenting Self-Efficacy Scale), and relationship measures (DAS-7, Couples' Illness Communication Scale, and Family Relationship Index). RESULTS: Of the 51 patients (57% female, 49% NHW, mean age 42 years) and spouses (43% female, 43% NHW, mean age of 42 years), approximately 50% couples endorsed psychological distress and were at risk for family dysfunction. Spouses reported significantly higher levels of parenting-related concerns (t = -2.0, p < 0.05) and anxiety (t = -2.8, p < 0.001) than patients. Parenting concerns were significantly associated with illness communication (r = -0.56, p < 0.001) and family function (r = -0.38, p < 0.001). Although the expected interactions between parenting concerns and relationship variables (i.e., illness communication, dyadic adjustment, and family function) were significant for depressive symptoms at p < 0.05, the associations were not in the expected direction. Relationship function buffered against depressive symptoms for those with low rather than high parenting concerns. CONCLUSIONS: Not only patients but also spouses report cancer-related parenting concerns. The associations between parenting concerns and distress were stronger for spouses than patients. Dual caregiving appears to be a particularly stressful role. Because relationship function was associated with parenting concerns, we suggest that parent support programs that are couple-based and include both parenting-specific and relationship-specific content may be most effective in reducing distress for this vulnerable population.

Does intervertebral disc degeneration in adolescent idiopathic scoliosis correlate with patient-reported pain scores? A review of 968 cases.

PURPOSE: Report the rate and severity of degenerative disc disease (DDD) in non-surgical adolescent idiopathic scoliosis (AIS) patients and correlate these findings with patient-reported symptomatology scores. Additionally, to quantify the rate of concurrent pathological radiological findings in this group. METHODS: This was a retrospective chart review study at a single tertiary centre. AIS patients aged 10-16 who had received a whole spine MRI between September 2007 and January 2019 and who had not received surgical intervention to their spine were included. MRI scan reports were screened to extract those who had evidence of DDD. These were then reviewed by a blinded second reviewer who graded every disc using the Pfirrmann grading system. SRS-22 scores were extracted for patients when available. RESULTS: In total, 968 participants were included in the study. Of these, 93 (9.6%) had evidence of DDD, which was Pfirrmann grade ≥ 3 in 28 (2.9%). The most commonly affected level was L5/S1 (59.1% of DDD cases). A total of 55 patients (5.7%) had evidence of syringomyelia, 41 (3.4%) had evidence of spondylolisthesis (all L5/S1), 14 (1.4%) had bilateral L5 pars defects, and 5 (0.5%) had facet joint degeneration. Spondylolisthesis and bilateral pars defects were more common in patients with DDD identified on MRI scan (p < 0.001 and p = 0.04, respectively). Function (p = 0.048) and pain (p = 0.046) scores were worse in patients with DDD. CONCLUSION: We present a baseline for the rate and severity of DDD in the non-operative AIS cohort. This should assist in decision-making and counselling of patients prior to surgery. LEVEL OF EVIDENCE: III.

Responsiveness of Subjective and Objective Measures of Pain and Function Following Operative Interventions for Musculoskeletal Conditions: A Narrative Review.

OBJECTIVE: Musculoskeletal (MSK) disorders affect ~50% of US adults and 75% of those over the age of 65, representing a sizable economic and disability burden. Outcome measures, both objective and subjective, help clinicians and investigators determine whether interventions to treat MSK conditions are effective. This narrative review qualitatively compared the responsiveness of different types of outcome measures, a key measurement characteristic that assesses an outcome measure's ability to detect change in patient status. METHODS: We evaluated elective orthopedic interventions as a model for assessing responsiveness because the great majority of patients improves following surgery. We searched for articles reporting responsiveness (quantified as effect size [ES]) of subjective and objective outcome measures after orthopedic surgery and included 16 articles reporting 17 interventions in this review. RESULTS: In 14 of 17 interventions, subjective function measures had an ES 10% greater than that of objective function measures. Two reported a difference in ES of <10%. The sole intervention that demonstrated higher ES of objective function used a composite measure. Sixteen interventions reported measures of subjective pain and/or mixed measures and subjective function. In nine interventions, subjective pain had a higher ES than subjective function by >10%, in three, subjective function had a higher ES than subjective pain by >10%, and in the remaining four, the difference between pain and function was <10%. CONCLUSION: These findings reinforce the clinical observation that subjective pain generally changes more than function following elective orthopedic surgery. They also suggest that subjective function measures are more responsive than objective function measures, and composite scores may be more responsive than individual performance tests.

Enhanced Mitochondrial Targeting and Inhibition of Pyroptosis with Multifunctional Metallopolyphenol Nanoparticles in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain, characterized by excessive reactive oxygen species generation and inflammation-induced pyroptosis. Unfortunately, there are currently no specific molecules or materials available to effectively delay IVDD. This study develops a multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on PG@Cu nanoparticles via a Schiff base bond, imparts multifunctionality to the metal polyphenol particles (PG@Cu-FP). PG@Cu-FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting of mitochondria to scavenge excess reactive oxygen species. The scavenging activity against reactive oxygen species originates from the polyphenol-based structures within the nanoparticles. Furthermore, Pyroptosis is effectively blocked by inhibiting Gasdermin mediated pore formation and membrane rupture. PG@Cu-FP successfully reduces the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome by inhibiting Gasdermin protein family (Gasdermin D, GSDMD) oligomerization, leading to reduced expression of Nod-like receptors. This multifaceted approach demonstrates higher efficiency in inhibiting Pyroptosis. Experimental results confirm that PG@Cu-FP preserves disc height, retains water content, and preserves tissue structure. These findings highlight the potential of PG@Cu-FP in improving IVDD and provide novel insights for future research in IVDD treatments.

New approach to testing treatments for osteoarthritis: FastOA.

Animal models of post traumatic osteoarthritis have shown many promising treatments for disease, but human trials have mostly failed to identify effective treatments. This viewpoint suggests that the frequent failure of drug and treatment development in osteoarthritis is due, in part, to the advanced stage of disease of patients in trials and suggests that mirroring the animal model approach might be more successful. It suggests a path forward by enriching trial enrollees with those likely to develop post traumatic OA quickly.

Predictors of Return to Activity at 2 Years After Anterior Cruciate Ligament Reconstruction Among Patients With High Preinjury Marx Activity Scores: A MOON Prospective Cohort Study.

BACKGROUND: Predictors of return to activity after anterior cruciate ligament reconstruction (ACLR) among patients with relatively high preinjury activity levels remain poorly understood. PURPOSE/HYPOTHESIS: The purpose of this study was to identify predictors of return to preinjury levels of activity after ACLR, defined as achieving a Marx activity score within 2 points of the preinjury value, among patients with Marx activity scores of 12 to 16 who had been prospectively enrolled in the Multicenter Orthopaedic Outcomes Network (MOON) cohort. We hypothesized that age, sex, preinjury activity level, meniscal injuries and/or procedures, and concurrent articular cartilage injuries would predict return to preinjury activity levels at 2 years after ACLR. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: All unilateral ACLR procedures from 2002 to 2008 performed in patients enrolled in the MOON, with preinjury Marx activity scores ranging from 12 to 16, were evaluated with a specific focus on return to preinjury activity levels at 2 years postoperatively. Return to activity was defined as a Marx activity score within 2 points of the preinjury value. The proportion of patients able to return to preinjury activity levels was calculated, and multivariable modeling was performed to identify risk factors for patients' inability to return to preinjury activity levels. RESULTS: A total of 1188 patients were included in the final analysis. The median preinjury Marx activity score was 16 (interquartile range, 12-16). Overall, 466 patients (39.2%) were able to return to preinjury levels of activity, and 722 patients (60.8%) were not able to return to preinjury levels of activity. Female sex, smoking at the time of ACLR, fewer years of education, lower 36-Item Short Form Health Survey Mental Component Summary scores, and higher preinjury Marx activity scores were predictive of patients' inability to return to preinjury activity levels. Graft type, revision ACLR, the presence of medial and/or lateral meniscal injuries, a history of meniscal surgery, the presence of articular cartilage injuries, a history of articular cartilage treatment, and the presence of high-grade knee laxity were not predictive of a patient's ability to return to preinjury activity level. CONCLUSION: At 2 years after ACLR, most patients with high preinjury Marx activity scores did not return to their preinjury level of activity. The higher the preinjury Marx activity score that a patient reported at the time of enrollment, the less likely he/she was able to return to preinjury activity level. Smoking and lower mental health at the time of ACLR were the only modifiable risk factors in this cohort that predicted an inability to return to preinjury activity levels. Continued effort and investigation are required to maximize functional recovery after ACLR in patients with high preinjury levels of activity.

Radiographic Changes Five Years After Treatment of Meniscal Tear and Osteoarthritic Changes.

OBJECTIVE: Meniscal tear in persons aged ≥45 years is typically managed with physical therapy (PT), and arthroscopic partial meniscectomy (APM) is offered to those who do not respond. Prior studies suggest APM may be associated with greater progression of radiographic changes. METHODS: We assessed changes between baseline and 60 months in the Kellgren-Lawrence (KL) grade and OARSI radiographic score (including subscores for joint space narrowing and osteophytes) in subjects aged 45-85 years enrolled into a seven-center randomized trial comparing outcomes of APM with PT for meniscal tear, osteoarthritis changes, and knee pain. The primary analysis classified subjects according to treatment received. To balance APM and PT groups, we developed a propensity score and used inverse probability weighting (IPW). We imputed a 60-month change in the OARSI score for subjects who underwent total knee replacement (TKR). In a sensitivity analysis, we classified subjects by randomization group. RESULTS: We analyzed data from 142 subjects (100 APM, 42 PT). The mean ± SD weighted baseline OARSI radiographic score was 3.8 ± 3.5 in the APM group and 4.0 ± 4.9 in the PT group. OARSI scores increased by a mean of 4.1 (95% confidence interval [95% CI] 3.5-4.7) in the APM group and 2.4 (95% CI 1.7-3.2) in the PT group (P < 0.001) due to changes in the osteophyte component. We did not observe statistically significant differences in the KL grade. Sensitivity analyses yielded similar findings to the primary analysis. CONCLUSION: Subjects treated with APM had greater progression in the OARSI score because of osteophyte progression but not in the KL grade. The clinical implications of these findings require investigation.

How Pol α-primase is targeted to replisomes to prime eukaryotic DNA replication.

During eukaryotic DNA replication, Pol α-primase generates primers at replication origins to start leading-strand synthesis and every few hundred nucleotides during discontinuous lagging-strand replication. How Pol α-primase is targeted to replication forks to prime DNA synthesis is not fully understood. Here, by determining cryoelectron microscopy (cryo-EM) structures of budding yeast and human replisomes containing Pol α-primase, we reveal a conserved mechanism for the coordination of priming by the replisome. Pol α-primase binds directly to the leading edge of the CMG (CDC45-MCM-GINS) replicative helicase via a complex interaction network. The non-catalytic PRIM2/Pri2 subunit forms two interfaces with CMG that are critical for in vitro DNA replication and yeast cell growth. These interactions position the primase catalytic subunit PRIM1/Pri1 directly above the exit channel for lagging-strand template single-stranded DNA (ssDNA), revealing why priming occurs efficiently only on the lagging-strand template and elucidating a mechanism for Pol α-primase to overcome competition from RPA to initiate primer synthesis.

Supportive Care for Dual Caregivers who Care for Their Partner With Cancer and Their Young Children.

PURPOSE: Advanced cancer patients and their spouses who parent minor children report parenting concerns and increased psychological distress. This single-arm trial examined the feasibility and initial evidence for efficacy of a novel parent support program. METHODS: Patients with a metastatic solid malignancy and their spouses completed self-reported assessments of psychological distress (HADS), parenting concerns (PCQ) and efficacy (CaPSE) at baseline. Both patients and spouses jointly attended the first two sessions addressing illness communication and family routines. Spouses individually attended two additional sessions focusing on caregiver support and death preparedness. All four sessions were delivered via videoconference by a licensed psychological counselor. Dyads completed program evaluations and were reassessed six and 12 weeks postintervention. RESULTS: With a consent rate of 61%, 10 patients (50% female; 90% non-Hispanic White; mean age = 42 years) and their spouses (50% female; 70% non-Hispanic White; mean age = 42 years) completed the assessments. All patients and 90% of spouses attended all intervention sessions and evaluated the program favorably. Paired t-tests revealed significant improvements in patients' parenting concerns at the six weeks (P = 0.003) and parenting efficacy at the six weeks (P = 0.03) and 12 weeks (P = 0.03) follow-ups. For spouses, we found significant improvements in parenting efficacy (P < 0.001) and depressive symptoms (P = 0.04) at six weeks and parenting concerns at both six weeks (P = 0.006) and 12 weeks (P = 0.001) follow-ups. CONCLUSIONS: The initial testing of our parenting intervention yielded promising results regarding feasibility and an initial signal of intervention efficacy. Thus, a randomized controlled trial for further testing is warranted.

Living With an Advanced Cancer While Parenting Minor Children: A Needs Assessment Study.

BACKGROUND: Evidence-based interventions addressing the needs of couples co-parenting young children while facing an advanced cancer diagnosis are lacking. Thus, this study seeks to identify parenting-related intervention needs and delivery preferences of advanced cancer patients and their spouses/co-parents. METHODS: Twenty-one couples completed quantitative measures of cancer-related parenting concerns, relationship and family functioning, and service needs along with individual semi-structured interviews. RESULTS: Patients (mean age=44 years, 48% female, 91% White) and spouses (mean age=45 years, 52% female, 91% White) reported family distress (62% of couples) and marital distress (29% of couples). Parenting concerns were generally high with patients revealing concerns particularly regarding the practical impact of the cancer on the child(ren). Spouses rated concerns about the co-parent significantly higher (P<.001) than patients. Parenting concerns were inversely associated with relationship (P<.001 for patients; P=.03 for spouses) and family functioning (P<.001 for patients). Themes identified through qualitative interviews include needs related to maintenance of family routines and traditions, childcare, transportation, meals, home maintenance, and finances. Couples who endorsed marital distress also indicated a need for conflict resolution skills. All patients and 89% of spouses would like to receive parenting-related education/services; up to 50% of couples preferred targeted, self-led readings without therapist support; and up to 50% desired counseling sessions indicating a preference towards dyadic and video conferenced intervention delivery. CONCLUSIONS: The delivery of optimal supportive care involves a family-focused perspective such as screening for parenting status and referrals to social work services to address the need of tangible resources and manage parenting-related distress.

The Corticosteroid Meniscectomy Trial of Extended-Release Triamcinolone Injection After Arthroscopic Partial Meniscectomy: Protocol for a Double-Blind Randomized Controlled Trial.

Background: Meniscal tear in older adults often accompanies knee osteoarthritis and is commonly treated with arthroscopic partial meniscectomy (APM) when patients have persistent pain after a trial of physical therapy. Cross-sectional evidence suggests that synovitis is associated with baseline pain in this patient population, but little is known about the relationship between synovitis and postoperative recovery or progression of knee osteoarthritis. Purpose/Hypothesis: Intra-articular extended-release triamcinolone may reduce inflammation and thereby improve outcomes and slow disease progression. This article presents the rationale behind the Corticosteroid Meniscectomy Trial (CoMeT) and describes its study design and implementation strategies. Study Design: Randomized controlled trial. Methods: CoMeT is a 2-arm, 3-center, randomized placebo-controlled trial designed to establish the clinical efficacy of extended-release triamcinolone administered via intra-articular injection immediately after APM. The primary outcome is change in Knee injury and Osteoarthritis Outcome Score Pain subscore at 3-month follow-up. Synovial biopsy, joint fluid aspirate, and urine and blood sample analyses will examine the associations between various objective measures of baseline inflammation and pre- and postoperative outcome measures and clinical responses to triamcinolone intervention. Quantitative 3-T magnetic resonance imaging will evaluate cartilage and meniscal composition and 3-dimensional bone shape to detect early joint degeneration. Results: We discuss methodologic innovations and challenges. Conclusion: To our knowledge, this is the first randomized double-blind clinical trial that will analyze the effect of extended-release triamcinolone acetonide on pain, magnetic resonance imaging measures of structural change and effusion/synovitis, soluble biomarkers, and synovial tissue transcriptomics after APM.

End-of-Life Care, Symptom Burden, and Quality of Life in Couples Facing Stage IV Lung Cancer: The Role of Patient and Spousal Psychospirituality and Discussions Around Fear of Death and Disease Progression.

Background: As patients live longer with stage IV nonsmall cell lung cancer, correlates of end-of-life (EOL) care and experience are increasingly relevant. Methods: We, therefore, prospectively examined associations among psychospirituality (Center for Epidemiologic Studies Depression Scale, Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being), discussions around fear of death and disease progression, and hospital-based EOL care in patients and caregivers. Patients additionally reported symptom burden (MD Anderson Symptom Inventory-Lung Cancer total) and quality of life (QOL) (quality-of-life at EOL). Results: Of the baseline patients (n = 75), 32% were alive at time of the analyses (mean = 4.6 years postbaseline). Deceased patients (n = 51) were middle aged (mean = 65.3 years) and non-Hispanic White (81%). Caregiver spiritual well-being (r = 0.34, p = 0.02) and depression (r = -0.31, p = 0.03) were associated with EOL care metrics. Patients who "held back" more of their fear of death or disease progression experienced greater symptom burden (r = 0.41, p < 0.001) and poorer QOL (r = -0.44, p < 0.001). Conclusion: For couples facing prolonged metastatic disease, psychospirituality is highly relevant to EOL care with potential sequelae of withholding one's fear regarding death or disease progression.