Group Coping Intervention in Patients With Chronic Graft-Versus-Host Disease: A Pilot Randomized Clinical Trial.

BACKGROUND: More than half the long-term survivors of allogeneic hematopoietic cell transplantation develop chronic graft-versus-host disease (GVHD), a debilitating inflammatory syndrome. Supportive interventions to assist survivors in coping with chronic GVHD are critically needed. PATIENTS AND METHODS: We conducted a pilot randomized clinical trial of a multidisciplinary group intervention (Horizons Program; n=39) versus minimally enhanced usual care (n=41) for patients with moderate or severe chronic GVHD. Horizons participants received 8 weekly sessions about GVHD and coping co-led by a transplant clinician and a behavioral health expert via a secure videoconferencing platform. Participants completed the following surveys before randomization, at 10 weeks, and at 18 weeks: Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) for quality of life (QoL), Lee Symptom Scale for symptom burden, and Hospital Anxiety and Depression Scale-Depression Symptoms (HADS) for mood. The primary endpoint was feasibility (≥50% enrollment, ≥80% attendance in half the sessions for the Horizons arm only, and ≥80% retention). We also explored preliminary efficacy of the Horizons intervention on changes in patient-reported outcomes with linear mixed effects models and estimates of effect size at 10 weeks. RESULTS: We enrolled and registered 80 (67.2%) of 119 eligible patients (mean age, 62 years; 48.8% female). Of the participants in the Horizons Program, 84.6% attended at least half the sessions. Of registered participants, 91.3% completed assessment follow-ups (Horizons, 35/39 [89.7%]; minimally enhanced usual care, 38/41 [92.7%]). Horizons participants reported improvements in QoL (b = 2.24; d=0.53), anxiety symptoms (b = -0.10; d=0.34), and depression symptoms (b = -0.71; d=0.44) compared with participants who received minimally enhanced usual care. CONCLUSIONS: Participation in a multidisciplinary group intervention study was feasible for patients with chronic GVHD, with promising signals for improving QoL and mood. A full-scale efficacy trial is needed to confirm effects on patient-reported outcomes.

The effect of concurrent cervical spine degenerative disease on the outcome of rotator cuff repair: a national database study.

BACKGROUND: Cervical spine degenerative disease (CSD) can cause shoulder pain, potentially confounding the management of patients with rotator cuff tears. This study aimed to investigate the relationships between CSD and rotator cuff repair (RCR). METHODS: A national administrative database (PearlDiver) was used to study 4 patient cohorts: (1) RCR only (RCRo), (2) RCR with concurrent CSD (RCRC), (3) RCR after a cervical spine procedure (RCRA), and (4) RCR before a cervical spine procedure (RCRB). The outcomes of RCR were compared using multivariable logistic regression, controlling for age, sex, and Elixhauser Comorbidity Index, as well as preoperative opioid utilization in the analysis of opioid use. RESULTS: Between 2010 and 2021, a total of 889,977 patients underwent RCR. Of these patients, 784,230 (88%) underwent RCRo whereas 105,747 (12%) underwent RCRC, of whom 21,585 (2.4%) underwent cervical spine procedures (RCRA in 9670 [1.1%] and RCRB in 11,915 [1.3%]). At 2 years after RCR, compared with RCRo patients, RCRC patients had an increased risk of surgical-site infection (adjusted odds ratio [aOR] = 1.25, P = .0004), deep vein thrombosis (aOR = 1.17, P = .0002), respiratory complications (aOR = 1.19, P = .0164), and ipsilateral shoulder reoperations (débridement [aOR = 1.66, P < .0001], manipulation under anesthesia or arthroscopic lysis of adhesions [aOR = 1.23, P < .0001], distal clavicle excision [aOR = 1.78, P < .0001], subacromial decompression [aOR = 1.72, P < .0001], biceps tenodesis [aOR = 1.76, P < .0001], incision and drainage [aOR = 1.34, P = .0020], synovectomy [aOR = 1.48, P = .0136], conversion to shoulder arthroplasty [aOR = 1.62, P < .0001], revision RCR [aOR = 1.77, P < .0001], and subsequent contralateral RCR [aOR = 1.71, P < .0001]). At 2 years, compared with RCRC patients who did not undergo cervical spine procedures, RCRC patients who underwent cervical spine procedures had an increased risk of incision and drainage (aOR = 1.50, P = .0255), conversion to arthroplasty (aOR = 1.40, P < .0001), and revision RCR (aOR = 1.11, P = .0374), as well as a lower risk of contralateral RCR (aOR = 0.89, P = .0469). The sequence of cervical spine procedures did not affect the risk of shoulder reoperations. At 1 year, the risk of opioid use after RCR was less for RCRA patients compared with RCRB patients (aOR = 1.71 [95% confidence interval, 1.61-1.80; P < .0001] vs. aOR = 2.01 [95% confidence interval, 1.92-2.12; P < .0001]). CONCLUSION: Concurrent CSD has significant detrimental effects on RCR outcomes. Patients with concurrent CSD undergoing cervical spine procedures have a greater risk of ipsilateral shoulder reoperations but a decreased risk of contralateral RCR. The risk of prolonged opioid use was lower if RCR followed a cervical spine procedure. Concurrent CSD must be considered and possibly treated to optimize the outcomes of RCR.

Impact of Social Determinants of Health on Adolescent Idiopathic Scoliosis Curve Severity.

INTRODUCTION: Social determinants of health have been shown to influence the health and outcomes of pediatric patients. Adolescent idiopathic scoliosis (AIS) may be particularly sensitive to such factors as early diagnosis and treatment can obviate the need for surgical intervention. The purpose of this study was to analyze the effect that social determinants of health have on the severity of AIS at presentation and at the time of surgery. METHODS: A retrospective review was conducted for consecutive patients who underwent posterior spinal fusion for AIS from 2020 to 2022. Demographic data was collected, while insurance status (private vs. public) and childhood opportunity index (COI) categories (LOW vs. HIGH) were used as a proxy for socioeconomic status. Curve magnitude at the initial presentation and at the latest preoperative visit were recorded with a threshold of 25 to 40 degrees considered within the bracing range. Univariate and multivariate analysis was done to compare differences between subgroups as appropriate. RESULTS: A total of 180 patients with mean initial and preoperative major curve angles of 48 and 60 degrees were included. Statistically significant differences in race and insurance types were appreciated, with the LOW COI group having a higher proportion of underrepresented minority and publicly insured patients than the HIGH COI group ( P <0.001). Patients within the LOW COI group presented with an initial curve that was, on average, 6 degrees more severe than those within the HIGH group ( P =0.009) and a preoperative curve that was 4 degrees larger than those within the HIGH group ( P =0.015). Similarly, only 13% of patients within the LOW COI group presented with curves within the bracing threshold, compared with 31% in the HIGH COI group ( P =0.009). CONCLUSION: Socioeconomic status plays a significant role in the severity of AIS. Specifically, patients with lower COI tend to present with curve magnitudes beyond what is responsive to nonsurgical treatment, leading to larger curves at the time of surgery. Future work should focus on addressing social inequalities to optimize the treatment and outcomes of AIS patients. LEVEL OF EVIDENCE: Level III- Retrospective Comparative Study.

Classification and Treatment of Pediatric Capitellar Fractures.

BACKGROUND: Fractures of the capitellum are rare in children. The purpose of this study was to report fracture characteristics, treatment, and outcomes of pediatric capitellar fractures at a single children's hospital. We also aimed to update the classification of these fractures based on a large sample size by revising the Murthy (Boston) classification. METHODS: In a retrospective study at a single tertiary care children's hospital, fractures of the capitellum in patients below 18 years of age were queried and reviewed for demographics, injury characteristics, imaging, treatment, outcomes, and complications. Three surgeons reviewed all imaging to classify the fractures and assess interobserver and intraobserver reliability. RESULTS: Forty-four patients (25 male) with capitellar fractures with a mean age of 11.7±3.7 years were identified. Seven fractures did not belong to an existing type and were grouped into a new type IV capitellar fracture, defined as LCL avulsions with extension to the articular surface of the capitellum. We found good to excellent inter-rater and intrarater reliability for the new classification system. Our raters believed that cross-sectional imaging was essential to classifying fractures in 84% of the cases. Thirty-three of 44 patients underwent early surgical intervention, with favorable outcomes. Five patients presented late with substantial elbow contracture and malunion and were treated surgically with the excision of the fragment. CONCLUSIONS: The new classification of pediatric capitellar fractures is more comprehensive and offers good to excellent reliability. We found excellent outcomes in the majority of cases with early diagnosis and management, but substantial risk for complications with missed and delayed diagnosis. Malunion and subsequent loss of ROM were the most common presentations of a missed diagnosis, which can be surgically treated with favorable outcomes. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Ketorolac and bone healing: a review of the basic science and clinical literature.

Although the efficacy of ketorolac in pain management and the short duration of use align well with current clinical practice guidelines, few studies have specifically evaluated the impact of ketorolac on bony union after fracture or surgery. The purpose of this study was to review the current basic science and clinical literature on the use of ketorolac for pain management after fracture and surgery and the subsequent risk of delayed union or nonunion. Animal studies demonstrate a dose-dependent risk of delayed union in rodents treated with high doses of ketorolac for 4 weeks or greater; however, with treatment for 7 days or low doses, there is no evidence of risk of delayed union or nonunion. Current clinical evidence has also shown a dose-dependent increased risk of pseudoarthrosis and nonunion after post-operative ketorolac administration in orthopedic spine surgery. However, other orthopedic subspecialities have not demonstrated increased risk of delayed union or nonunion with the use of peri-operative ketorolac administration. While evidence exists that long-term ketorolac use may represent risks with regard to fracture healing, insufficient evidence currently exists to recommend against short-term ketorolac use that is limited to the peri-operative period. LEVEL OF EVIDENCE V: Narrative Review.

Unveiling Enhanced Electrostatic Repulsion in Silica Nanosphere Assembly: Formation Dynamics of Body-Centered-Cubic Colloidal Crystals.

We demonstrate the effective establishment of long-range electrostatic interactions among colloidal silica nanospheres through acid treatment, enabling their assembly into colloidal crystals at remarkably low concentrations. This novel method overcomes the conventional limitation in colloidal silica assembly by removing entrapped NH4+ ions and enhancing the electrical double layer (EDL) thickness, offering a time-efficient alternative to increase electrostatic interactions compared with methods like dialysis. The increased EDL thickness facilitates the assembly of SiO2 nanospheres into a body-centered-cubic lattice structure at low particle concentrations, allowing for broad spectrum tunability and high tolerance to particle size polydispersity. Further, we uncover a disorder-order transition during colloidal crystallization at low particle concentrations, with the optimal concentration for crystal formation governed by both thermodynamic and kinetic factors. This work not only provides insights into assembly mechanisms but also paves the way for the design and functionalization of colloidal silica-based photonic crystals in diverse applications.

Psychological mobile app for patients with acute myeloid leukemia: A pilot randomized clinical trial.

BACKGROUND: Patients with acute myeloid leukemia (AML) experience a substantial decline in quality of life (QoL) and mood during their hospitalization for intensive chemotherapy, yet few interventions have been developed to enhance patient-reported outcomes during treatment. METHODS: We conducted a pilot randomized trial (ClinicalTrials.gov identifier NCT03372291) of DREAMLAND, a psychological mobile application for patients with a new diagnosis of AML who are receiving intensive chemotherapy. Patients were randomly assigned to DREAMLAND or usual care. DREAMLAND included four required modules focused on: (1) supportive psychotherapy to help patients deal with the initial shock of diagnosis, (2) psychoeducation to manage illness expectations, (3) psychosocial skill-building to promote effective coping, and (4) self-care. The primary end point was feasibility, which was defined as ≥60% of eligible patients enrolling and 60% of those enrolled completing ≥60% of the required modules. We assessed patient QoL (the Functional Assessment of Cancer Therapy-Leukemia), psychological distress (the Hospital Anxiety and Depression Scale and the Patient Health Questionnaire-9), symptom burden (the Edmonton Symptom Assessment Scale), and self-efficacy (the Cancer Self-Efficacy Scale) at baseline and at day 20 after postchemotherapy. RESULTS: We enrolled 60 of 90 eligible patients (66.7%), and 62.1% completed ≥75% of the intervention modules. At day 20 after chemotherapy, patients who were randomized to DREAMLAND reported improved QoL scores (132.06 vs. 110.72; p =.001), lower anxiety symptoms (3.54 vs. 5.64; p = .010) and depression symptoms (Hospital Anxiety and Depression Scale: 4.76 vs. 6.29; p = .121; Patient Health Questionnaire-9: 4.62 vs. 8.35; p < .001), and improved symptom burden (24.89 vs. 40.60; p = .007) and self-efficacy (151.84 vs. 135.43; p = .004) compared with the usual care group. CONCLUSIONS: A psychological mobile application for patients with newly diagnosed AML is feasible to integrate during hospitalization for intensive chemotherapy and may improve QoL, mood, symptom burden, and self-efficacy.

Coping and Perception of Prognosis in Patients With Indolent Non-Hodgkin's Lymphoma.

BACKGROUND: Indolent non-Hodgkin's lymphomas (iNHL) are a heterogenous group of mostly incurable diseases with prolonged illness courses and prognostic uncertainty. Yet, studies evaluating coping and perception of prognosis are limited. METHODS: We conducted a cross-sectional study of adults newly diagnosed with iNHL in the past 3 months at a single academic center. We assessed quality of life (QOL: Functional Assessment of Cancer Therapy-General), psychological symptoms (Hospital Anxiety and Depression Scale), coping (Brief-COPE), and perception of prognosis (Prognosis Awareness Impact Scale). RESULTS: We enrolled 70.6% (48/68) of eligible patients. Patients had older age (mean = 66.9,sd = 10.5), were female (60.4%), predominantly identified as White (85.4%), and had at least received a college degree (75%). Chronic lymphocytic leukemia (39.6%) and follicular lymphoma (33.3%) were the most common diagnoses. Overall, 27.1% and 14.6% of patients reported clinically significant anxiety and PTSD symptoms, respectively. Patients highly utilized acceptance (56.2%), seeking emotional support (47.9%), and denial (47.9%) as coping strategies at diagnosis. While 66.7% of patients recalled their oncologist assessment of illness as incurable, only 35.4% reported that the illness is unlikely to be cured. Overall, 45.8% indicated that they were worried about prognosis and 31.2% reported perseverating on their prognosis. Higher emotional coping with prognosis was associated with fewer anxiety (B = -0.6, SE = 0.2, P < .001), depression (B = -0.3, SE = .1, P = .005), and PTSD (B = -1.3, SE = 0.4, P < .001) symptoms and better QOL (B = 1.7, SE = 0.4, P < .001). DISCUSSION: Patients with iNHL report substantial psychological distress, a diversity of coping strategies, and complex cognitive understanding of their prognosis. Interventions, which address prognostic uncertainty and promote positive emotional coping with prognosis, may ameliorate psychological distress in this population.

Does Skeletal Maturity Predict the Pattern of Tibial Tubercle Avulsion Fracture?

BACKGROUND: Proximal tibial physeal development and closure is thought to relate to tibial tubercle avulsion fracture (TTAF) patterns. Prior work has yet to formally evaluate the relationship between skeletal maturity and fracture pattern.  Using 2 knee radiograph-derived skeletal maturity assessments [growth remaining percentage (GRP) and epiphyseal union stage], we examined their association with TTAF injury patterns using the Ogden and Pandya fracture classifications. We hypothesized that different TTAF injuries would occur during unique periods of skeletal development. METHODS: Pediatric patients sustaining TTAFs treated at a single institution (2008-2022) were identified using diagnostic and procedural coding. Demographics and injury characteristics were collected. Radiographs were reviewed to assign epiphyseal union stage, Ogden and Pandya classifications and for measurements to calculate GRP. Univariate analyses examined the relationship between injury subgroups, patient demographics, and skeletal maturity assessments. RESULTS: Inclusion criteria identified 173 patients with a mean age of 14.76 (SD: 1.78) and 2.95% (SD: 4.46%) of growth remaining. The majority of injuries were classified Ogden III/Pandya C. Most (54.9%) were the result of the axial loading mechanism. Ogden groups showed no significant differences across all patient characteristics studied including age and GRP. With the exception of Pandya A fractures, we did not identify a direct relationship between GRP, age, and Pandya groups. Epiphyseal union stage differed for Pandya A and D groups. CONCLUSIONS: A predictable pattern in TTAF characteristics across skeletal (GRP), epiphyseal union, or chronologic age was not identified in this study. Distal apophyseal avulsions (Ogden I/II and Pandya A/D) occurred across a broad chronologic and skeletal age range. No differences were identified in epiphyseal or posterior extension (Ogden III/IV and Pandya B/C) injuries. Although differences in age and GRP were identified among Pandya As, this is thought to be due to the degree of skeletal immaturity that is a prerequisite for differentiation from Pandya Ds. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Risk of Dislocation and Revision Following Primary Total Hip Arthroplasty in Patients With Prior Lumbar Fusion With Spinopelvic Fixation.

BACKGROUND: The effect of spinopelvic fixation in addition to lumbar spinal fusion (LSF) on dislocation/instability and revision in patients undergoing primary total hip arthroplasty (THA) has not been reported previously. METHODS: The PearlDiver Research Program was used to identify patients aged 30 and above undergoing primary THA who received (1) THA only, (2) THA with prior single-level LSF, (3) THA with prior 2-5 level LSF, or (4) THA with prior LSF with spinopelvic fixation. The incidence of THA revision and dislocation/instability was compared through logistic regression and Chi-squared analysis. All regressions were controlled for age, gender, and Elixhauser Comorbidity Index (ECI). RESULTS: Between 2010 and 2018, 465,558 patients without history of LSF undergoing THA were examined and compared to 180 THA patients with prior spinopelvic fixation, 5,299 with prior single-level LSF, and 1,465 with prior 2-5 level LSF. At 2 years, 7.8% of THA patients with prior spinopelvic fixation, 4.7% of THA patients with prior 2-5 level LSF, 4.2% of THA patients with prior single-level LSF, and 2.2% of THA patients undergoing only THA had a dislocation event or instability (P < .0001). After controlling for length of fusion, pelvic fixation itself was associated with higher independent risk of revision (at 2 years: 2-5 level LSF + spinopelvic fixation: aHR = 3.15, 95% CI 1.77-5.61, P < .0001 vs 2-5 level LSF with no spinopelvic fixation: aOR = 1.39, 95% CI 1.10-1.76, P < .0001). CONCLUSION: At 2 years, spinopelvic fixation in THA patients were associated with a greater than 3.5-fold increase in hip dislocation risk compared to those without LSF, and an over 2-fold increase in THA revision risk compared to those with LSF without spinopelvic fixation. LEVEL OF EVIDENCE: III.

Relationship Between Longitudinal Coping Strategies and Outcomes in Patients With Acute Myeloid Leukemia.

BACKGROUND: Patients with acute myeloid leukemia (AML) face an abrupt life-threatening illness and experience immense physical and psychological symptoms. However, no data describe how patients with AML cope longitudinally with their illness or the relationship between longitudinal coping and outcomes. METHODS: We conducted a secondary analysis of longitudinal data from 160 patients with high-risk AML enrolled in a supportive care intervention trial to describe coping strategies longitudinally across the illness course. We used the Brief COPE questionnaire, the Hospital Anxiety and Depression Scale, the Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian Version, and the Functional Assessment of Cancer Therapy-Leukemia to measure coping strategies, psychological distress, and quality of life (QoL) at baseline and at weeks 2, 4, 12, and 24 after diagnosis. Electronic health records were used to assess healthcare utilization and end-of-life (EoL) outcomes, and multivariate analyses were used to assess the relationship between coping and outcomes. RESULTS: Longitudinal utilization of approach-oriented coping strategies was significantly associated with less distress (anxiety: ß, -0.18; P<.001; depression symptoms: ß, -0.42; P<.001; PTSD symptoms: ß, -0.60; P<.001) and better QoL (ß, 2.00; P<.001). Longitudinal utilization of avoidant coping strategies was significantly associated with greater distress (anxiety: ß, 0.64; depression symptoms: ß, 0.54; PTSD symptoms: ß, 2.13; P<.001 for all) and worse QoL (ß, -4.27; P<.001). Although the use of approach-oriented and avoidant coping strategies was not significantly associated with hospitalization, chemotherapy administration, or hospice use in the last 30 days of life, approach-oriented coping was associated with lower odds of ICU admissions (odds ratio, 0.92; P=.049). CONCLUSIONS: Longitudinal use of approach-oriented coping strategies was associated with less psychological distress, better QoL, and a lower likelihood of ICU admission, suggesting a possible target for supportive oncology interventions. Coping strategies did not impact EoL outcomes, and further research is needed to elucidate which patient factors impact EoL decision-making.

Reverse total shoulder arthroplasty in patients 80 years and older: a national database analysis of complications and mortality.

BACKGROUND: Although reverse total shoulder arthroplasty (RSA) is considered a safe surgical option in elderly patients, large-scale analyses of complications and mortality after RSA in patients 80 years and older are scarce. The goals of the current study were to identify revision, complication, and early mortality rates after RSA in patients 80 years and older and compare these to younger patients. METHODS: The PearlDiver Database, which contains services rendered to Medicare, Medicaid, and commercial insurance patients, was queried for patients undergoing RSA using International Classification of Diseases, Ninth/Tenth Revision (ICD-9/ICD-10) procedure codes. Patients were separated into 2 groups based on their age: 80 years and older and <80 years of age. The incidence of revision arthroplasty, medical, and surgical complications after RSA were extracted. Multivariate regression was used to compare revision arthroplasty and complication rates between groups. Statistical significance was set at P <.05. RESULTS: A total of 29,430 cases of RSA were included, with 486 cases in patients 80 years and older (median age, 80 years; age range, 2 years). Patients 80 years and older had 1- and 2-year revision rates of 3.9% and 5.1%, compared with the younger cohort at 3.0% and 3.1%, respectively. In patients 80 years and older, there were higher rates of deep venous thrombosis (DVT) (odds ratio [OR] 2.87, 95% CI 1.5-4.97), urinary tract infection (OR 1.42, 95% CI 1.01-1.94), acute renal failure (OR 2.18, 95% CI 1.44-3.17), and pneumonia (OR 1.75, 95% CI 1.09-2.68) within 90 days postoperatively. Ninety-day surgical complications were similar between the cohorts; however, younger patients experienced higher rates of dislocation, stiffness, periprosthetic fracture, and implant complications 1 year postoperatively. Patients 80 years and older had a significantly higher 90-day mortality rate at 2.7% compared with 1.5% in younger patients (P = .002). CONCLUSIONS: RSA is a generally safe procedure even in patients 80 years and older, with low complication and revision rates. Patients 80 years and older had higher early mortality and medical complication rates, including DVT, renal failure, and pneumonia than patients <80 years of age. However, patients 80 years and older had lower rates of dislocation, periprosthetic fracture, and implant-related complication at 1 year postoperatively.

Preoperative Patient Education and Smaller Prescription Quantity Reduce Opioid Use After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis: Results of a Prospective Study.

BACKGROUND: Most opioids prescribed postoperatively are unused. Leftover opioids are a major source of nonmedical opioid use among adolescents. Postoperative opioid use has also been associated with prescription quantity. Our purpose was to evaluate the effect of preoperative patient education and implementation of evidence-based prescribing guidelines on opioid use and pain level after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). METHODS: AIS patients aged 10 to 17 years undergoing PSF were prospectively enrolled [postintervention cohort (POST-INT)]. Previous data on 77 patients showed median consumption of 29 doses of oxycodone after PSF [preintervention cohort (PRE-INT)]. All eligible patients during the study period were discharged with 30 doses of oxycodone and standard nonopioid analgesics. Only study participants received education on postoperative pain control. Demographics, radiographic/surgical data, pain level, and patient-reported outcomes were collected. Requests for opioid refills were documented. RESULTS: Forty-nine patients were enrolled. POST-INT was divided into low (L, ≤8 doses), average (AVE, 9-25), and high (H, >25) opioid use groups. Demographics, radiographic/surgical data, pain level, and patient-reported outcomes were similar between the groups. However, there was a difference in days of oxycodone use, doses consumed in the first week, and leftover doses ( P <0.001). Comparison to the PRE-INT L (≤16 doses), AVE (17 to 42), and high (H, >42) use groups showed that POST-INT L and AVE consumed less oxycodone (L: P =0.002; AVE: P <0.001). Also, the overall POST-INT cohort had fewer mean days of oxycodone use (5.6 vs. 8.9, P <0.001) and doses used in the first week (14 vs. 23, P <0.001) compared with the PRE-INT cohort. Subanalysis showed fewer study participants requested and received an opioid refill [3/49 patients (6%)] compared with eligible patients who declined to participate, withdrew, or missed enrollment [8/35 patients (23%)] ( P =0.045). CONCLUSIONS: Preoperative patient education and smaller prescription quantity successfully reduced opioid use while maintaining excellent pain control after PSF for AIS. Setting expectations regarding postoperative pain management is critical, as nonstudy participants were significantly more likely to request an opioid refill. LEVEL OF EVIDENCE: Level II-therapeutic.

Quadruped Gait and Regulation of Apoptotic Factors in Tibiofemoral Joints following Intra-Articular rhPRG4 Injection in Prg4 Null Mice.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4-PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene Prg4 served as a model that recapitulates the destructive arthrosis that involves biofouling of cartilage by serum proteins in lieu of Prg4. This study hypothesized that Prg4-deficient mice would demonstrate a quadruped gait change and decreased markers of mitochondrial dyscrasia, following intra-articular injection of both hindlimbs with recombinant human PRG4 (rhPRG4). Prg4-/- (N = 44) mice of both sexes were injected with rhPRG4 and gait alterations were studied at post-injection day 3 and 6, before joints were harvested for immunohistochemistry for caspase-3 activation. Increased stance and propulsion was shown at 3 days post-injection in male mice. There were significantly fewer caspase-3-positive chondrocytes in tibiofemoral cartilage from rhPRG4-injected mice. The mitochondrial gene Mt-tn, and myosin heavy (Myh7) and light chains (Myl2 and Myl3), known to play a cytoskeletal stabilizing role, were significantly upregulated in both sexes (RNA-Seq) following IA rhPRG4. Chondrocyte mitochondrial dyscrasias attributable to the arthrosis in CACP may be mitigated by IA rhPRG4. In a supporting in vitro crystal microbalance experiment, molecular fouling by albumin did not block the surface activity of rhPRG4.

Optimization of Biocompatibility for a Hydrophilic Biological Molecule Encapsulation System.

Despite considerable advances in recent years, challenges in delivery and storage of biological drugs persist and may delay or prohibit their clinical application. Though nanoparticle-based approaches for small molecule drug encapsulation are mature, encapsulation of proteins remains problematic due to destabilization of the protein. Reverse micelles composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) in low-viscosity alkanes have been shown to preserve the structure and stability of a wide range of biological macromolecules. Here, we present a first step on developing this system as a future platform for storage and delivery of biological drugs by replacing the non-biocompatible alkane solvent with solvents currently used in small molecule delivery systems. Using a novel screening approach, we performed a comprehensive evaluation of the 10MAG/LDAO system using two preparation methods across seven biocompatible solvents with analysis of toxicity and encapsulation efficiency for each solvent. By using an inexpensive hydrophilic small molecule to test a wide range of conditions, we identify optimal solvent properties for further development. We validate the predictions from this screen with preliminary protein encapsulation tests. The insight provided lays the foundation for further development of this system toward long-term room-temperature storage of biologics or toward water-in-oil-in-water biologic delivery systems.

Flower orientation influences floral temperature, pollinator visits and plant fitness.

Effective insect pollination requires appropriate responses to internal and external environmental cues in both the plant and the pollinator. Helianthus annuus, a highly outcrossing species, is marked for its uniform eastward orientation of mature pseudanthia, or capitula. Here we investigate how this orientation affects floral microclimate and the consequent effects on plant and pollinator interactions and reproductive fitness. We artificially manipulated sunflower capitulum orientation and temperature in both field and controlled conditions and assessed flower physiology, pollinator visits, seed traits and siring success. East-facing capitula were found to have earlier style elongation, pollen presentation and pollinator visits compared with capitula manipulated to face west. East-facing capitula also sired more offspring than west-facing capitula and under some conditions produced heavier and better-filled seeds. Local ambient temperature change on the capitulum was found to be a key factor regulating the timing of style elongation, pollen emergence and pollinator visits. These results indicate that eastward capitulum orientation helps to control daily rhythms in floral temperature, with direct consequences on the timing of style elongation and pollen emergence, pollinator visitation, and plant fitness.

Increased Medical and Implant-Related Complications in Total Hip Arthroplasty Patients With Underlying Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been associated with impaired bone metabolism. The purpose of this study is to investigate rates of readmission, respiratory complications, implant-related complications, and revision after total hip arthroplasty (THA) in patients with and without underlying COPD. METHODS: The PearlDiver Mariners database was used to divide patients undergoing primary THA (CPT-27130) into two cohorts: 1) THA with COPD (including asthma) or 2) THA without COPD. The incidence of 30-day readmission, COPD exacerbation, pneumonia, other respiratory complications as well as dislocations, mechanical loosening, and joint prosthetic infection was calculated through logistic regression. The risk of THA revision was also assessed through Cox-proportional hazards regression. All regression controlled for age, gender, and medical comorbidities found to be associated with COPD. RESULTS: Between 2010 and 2018, 97,784 THA patients with COPD and 338,243 THA patient without COPD were studied. THA patients with COPD had higher risk of 30-day readmission (aOR = 1.17, 95% CI 1.11-1.23, P < .0001). There was higher risk of 30-day pneumonia (aOR = 2.07, 95% CI 1.76-2.44, P < .0001). THA patients with COPD also faced higher risk of 30-day dislocations (aOR = 1.31, 95% CI 1.19-1.45, P < .0001), joint prosthetic infections (aOR = 1.25, 95% CI 1.14-1.37, P < .0001), and periprosthetic fracture (aOR = 1.19, 95% CI 1.07-1.32, P = .0015). Regarding revisions, 3.3% of THA patients with COPD underwent THA revision at 1 year, a higher risk than THA patients without COPD (aOR = 1.11, 95% CI 1.06-1.16, P < .0001). CONCLUSION: Patients undergoing THA with underlying COPD face a higher rate of comorbidities, respiratory complications, implant complications, and revision surgeries, than patients without COPD. LEVEL OF EVIDENCE: III.

Total Hip Arthroplasty After Hip Arthroscopy Has Increased Complications and Revision Risk.

BACKGROUND: There has been an increase in hip arthroscopy (HA) over the last decade. After HA, some patients may ultimately require a total hip arthroplasty (THA). However, there is a scarcity of research investigating the outcomes in patients undergoing THA with a history of ipsilateral HA. METHODS: The PearlDiver research program (www.pearldiverinc.com) was queried to capture all patients undergoing THA between 2015 and 2020. Propensity matching was performed to match patients undergoing THA with and without a history of ipsilateral THA. Rates of 30-day medical complications, 1-year surgical complications, and THA revision were compared using multivariate logistic regression. Kaplan-Meier analysis was conducted to estimate survival probabilities of each of the groups with patients undergoing THA . RESULTS: After propensity matching, cohorts of 1940 patients undergoing THA without prior HA and 1940 patients undergoing a THA with prior HA were isolated for analysis. The mean time from HA to THA was 1127 days (standard deviation 858). Patients with a history of ipsilateral HA had an increased risk for dislocation (odds ratio [OR] 1.56, P = .03) and overall decreased implant survival within 4 years of undergoing THA (OR 1.53; P = .05). Furthermore, our data demonstrate the timing of previous HA to be associated with the risk of complications, as illustrated by the increased risk for dislocation (OR 1.75, P = .03), aseptic loosening (OR 2.18, P = .03), and revision surgery at 2 (OR 1.92, P = .02) and 4 years (OR 2.05, P = .01) in patients undergoing THA within 1 year of HA compared twitho patients undergoing THA more than 1 year after HA or with no previous history of HA. CONCLUSION: Patients undergoing THA after HA are at an increased risk for surgical complications, as well as the need for revision surgery.

Geographic-Level Association of Contemporary Changes in Localized and Metastatic Prostate Cancer Incidence in the Era of Decreasing PSA Screening.

Decreased prostate-specific antigen screening since 2008 has generated much concern, including report of recent increase in metastatic prostate cancer incidence among older men. Although increased metastatic disease was temporally proceeded by decreased screening and decreased localized prostate cancer at diagnosis, it is unclear whether the 2 trends are geographically connected. We therefore used the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database to assess geographic-specific associations between changes in localized (2008-2011) and later changes in metastatic prostate cancer incidence (2012-2015). We examined trends from 200 health-care service areas (HSAs) within SEER 18 registries. While on average for each HSA, localized incidence decreased by 27.4 and metastatic incidence increased by 2.3 per 100 000 men per year, individual HSA-level changes in localized incidence did not correlate with later changes in metastatic disease. Decreased detection of localized disease may not fully explain the recent increase in metastatic disease at diagnosis.

Phenylalkylamines in calcium channels: computational analysis of experimental structures.

Experimental 3D structures of calcium channels with phenylalkylamines (PAAs) provide basis for further analysis of atomic mechanisms of these important cardiovascular drugs. In the crystal structure of the engineered calcium channel CavAb with Br-verapamil and in the cryo-EM structure of the Cav1.1 channel with verapamil, the ligands bind in the inner pore. However, there are significant differences between these structures. In the crystal structure the ligand ammonium group is much closer to the ion in the selectivity-filter region Site 3, which is most proximal to the inner pore, than in the cryo-EM structure. Here we used Monte Carlo energy minimizations to dock PAAs in calcium channels. Our computations suggest that in the crystal structure Site 3 is occupied by a water molecule rather than by a calcium ion. Analysis of the published electron density map does not rule out this possibility. In the cryo-EM structures the ammonium group of verapamil is shifted from the calcium ion in Site 3 either along the pore axis, towards the cytoplasm or away from the axis. Our unbiased docking reproduced these binding modes. However, in the cryo-EM structures detergent and lipid molecules interact with verapamil. When we removed these molecules, the nitrile group of verapamil bound to the calcium ion in Site 3. Models of Cav1.2 with different PAAs suggest similar binding modes and direct contacts of the ligands electronegative atoms with the calcium ion in Site 3. Such interactions explain paradoxes in structure-activity relationships of PAAs.