Narrative analysis in individuals with Parkinson's disease following intensive voice treatment: secondary outcome variables from a randomized controlled trial.

Communication is often impaired in individuals with Parkinson's disease (PD), typically secondary to sensorimotor deficits impacting voice and speech. Language may also be diminished in PD, particularly for production and comprehension of verbs. Evidence exists that verb processing is influenced by motor system modulation suggesting that verb deficits in PD are underpinned by similarities in the neural representations of actions that span motor and semantic systems. Conversely, subtle differences in cognition in PD may explain difficulty in processing of complex syntactic forms, which increases cognitive demand and is linked to verb use. Here we investigated whether optimizing motor system support for vocal function (improving loudness) affects change in lexical semantic, syntactic, or informativeness aspects of spoken discourse. Picture description narratives were compared for 20 Control participants and 39 with PD, 19 of whom underwent Lee Silverman Voice Treatment (LSVT LOUD®). Treated PD narratives were also contrasted with those of untreated PD and Control participants at Baseline and after treatment. Controls differed significantly from the 39 PD participants for verbs per utterance, but this difference was largely driven by untreated PD participants who produced few utterances but with verbs, inflating their verbs per utterance. Given intervention, there was a significant increase in vocal loudness but no significant changes in language performance. These data do not support the hypothesis that targeting this speech motor system results in improved language production. Instead, the data provide evidence of considerable variability in measures of language production across groups, particularly in verbs per utterance.

ACAD9 treatment with bezafibrate and nicotinamide riboside temporarily stabilizes cardiomyopathy and lactic acidosis.

Pathogenic ACAD9 variants cause complex I deficiency. Patients presenting in infancy unresponsive to riboflavin have high mortality. A six-month-old infant presented with riboflavin unresponsive lactic acidosis and life-threatening cardiomyopathy. Treatment with high dose bezafibrate and nicotinamide riboside resulted in marked clinical improvement including reduced lactate and NT-pro-brain type natriuretic peptide levels, with stabilized echocardiographic measures. After a long stable period, the child succumbed from cardiac failure with infection at 10.5 months. Therapy was well tolerated. Peak bezafibrate levels exceeded its EC50. The clinical improvement with this treatment illustrates its potential, but weak PPAR agonist activity of bezafibrate limited its efficacy.

Sex differences in the structure and function of the vasopressin system in the ventral pallidum are associated with the sex-specific regulation of social play behavior in juvenile rats.

Vasopressin (AVP) regulates various social behaviors, often in sex-specific ways, including social play behavior, a rewarding behavior displayed primarily by juveniles. Here, we examined whether and how AVP acting in the brain's reward system regulates social play behavior in juvenile rats. Specifically, we focused on AVP signaling in the ventral pallidum (VP), a brain region that is a part of the reward system. First, we examined the organization of the VP-AVP system in juvenile rats and found sex differences, with higher density of both AVP-immunoreactive fibers and AVP V1a receptor (V1aR) binding in males compared to females while females show a greater number of V1aR-expressing cells compared to males. We further found that, in both sexes, V1aR-expressing cells co-express a GABA marker to a much greater extent (approx. 10 times) than a marker for glutamate. Next, we examined the functional involvement of V1aR-expressing VP cells in social play behavior. We found that exposure to social play enhanced the proportion of activated V1aR-expressing VP cells in males only. Finally, we showed that infusion of a specific V1aR antagonist into the VP increased social play behaviors in juvenile male rats while decreasing these behaviors in juvenile female rats. Overall, these findings reveal structural and functional sex differences in the AVP-V1aR system in the VP that are associated with the sex-specific regulation of social play behavior.

Literature Review: Support for caregivers of children on the ketogenic diet for epilepsy and other neurologic disorders.

Epilepsy affects millions of people and when medications are insufficient to maintain seizure control, individuals are diagnosed with refractory epilepsy (RE). Medical ketogenic diet therapy (KDT), a diet high in fat and low in carbohydrates and sufficient in protein, is a well-established treatment for RE. However, compliance is one of the main reasons for discontinuation of KDT and, with pediatric RE patients, the ability of informal caregivers, typically family members, to maintain diet adherence is vital for successful KDT treatment. The central role that informal caregivers play for effective KDT implementation is recognized, however, there is a need to elucidate the rationale and theoretical underpinnings of effective KDT caregiver support programs to inform best practices. Therefore, this systematic literature review aims to identify the existing fundamental understandings of KDT caregiver support to help build a foundation of theory-based knowledge to promote evidenced practice. After screening 137 publications, three studies that discussed potential underlying components of effective caregiver support were included in this review. These articles followed a similar approach as they 1) employed qualitative methods delving into caregiver needs, 2) findings highlighted the importance of support from family, friends, fellow caregivers and their child's medical team, and 3) the inclusion of caregiver support findings were a supplement to the main purpose of the manuscript. Research focused on KDT caregivers is in its infancy. There is a clear need for the systematic examination of support for KDT caregivers to build a foundation for effective support programs and to increase the access to quality support programming to foster KDT implementation, desirable patient outcomes, and caregiver well being. In this article we discuss opportunities to apply self-determination theory to the KDT caregiver support research and practice.

Comparing hospital vs. non-hospital-affiliated clinic adoption of abortion innovations and cash-pay availability during the COVID-19 pandemic: A secondary analysis of a United States nationwide survey.

OBJECTIVES: We examined differences between hospital-affiliated clinics and non-hospital-affiliated clinics (independent or Planned Parenthood clinics) regarding abortion service innovation and cash-pay availability in response to COVID-19. STUDY DESIGN: We analyzed data from all three phases of a longitudinal nationwide survey of abortion providers conducted by the Society of Family Planning. RESULTS: This study utilizes a convenience sample of 74 voluntarily participating clinics, representing 5% of clinics nationwide. Compared to non-hospital-affiliated clinics, hospital-affiliated clinics were more likely to initiate care innovations but were less likely to offer cash-pay during the pandemic. CONCLUSIONS: Both hospital-affiliated and non-hospital-affiliated clinics enacted patient-centered care innovations during the pandemic. Hospital-affiliated clinics were more likely to initiate innovative services, particularly surrounding telemedicine. Hospital-affiliated clinics can improve cash-pay availability to expand access to abortion care in times of national emergencies.

Routine Vaccination During Pregnancy Among People Living With HIV in the United States.

Importance: Pregnancy represents a window of opportunity for vaccination due to established maternal and fetal benefits of vaccination. Little is known about receipt of routinely recommended vaccines in pregnancy, specifically tetanus, diphtheria, plus acellular pertussis (Tdap) and influenza, among pregnant people living with HIV (PLHIV). Objective: To estimate prevalence of vaccination receipt among pregnant people with HIV (PLHIV) and identify demographic and clinical characteristics associated with vaccination. Design, Setting, and Participants: This multicenter cohort study included women participating in Women's Health Study (WHS) of the Surveillance Monitoring for ART Toxicities (SMARTT) Study of the Pediatric HIV/AIDS Cohort Study. The network has been enrolling pregnant PLHIV at 22 US sites since 2007. Participants for this study enrolled between December 2017 and July 2019. Data analysis was conducted from October 2021 to March 2022. Exposure: Data on vaccination in pregnancy were collected through medical record abstraction. Main Outcomes and Measures: Vaccination receipt was defined as Tdap vaccination received at less than 36 weeks' gestation and influenza vaccination at any gestational age, based on current guidelines. Log-binomial and modified Poisson regression models with generalized estimating equations were fit to identify factors associated with successful receipt of (1) Tdap, (2) influenza, and (3) both vaccinations. Results: A total of 310 pregnancies among 278 people participating in the WHS were included (mean [SD] age, 29.5 [6.1] years; 220 [71%] Black, 77 [25%] Hispanic, and 77 [25%] race and ethnicity other than Black; 64 [21%] with perinatally acquired HIV). Less than one-third of pregnancies were vaccinated as recommended (Tdap, 32.6% [95% CI, 27.4%-38.1%]; influenza, 31.6% [95% CI, 26.5%-37.1%]; both, 22.6% [95% CI, 18.0%-27.6%]). People living with perinatally acquired HIV, those who did not identify as Black, or those who were multiparous had adjusted risk ratios (aRRs) less than 1, while older PLHIV had aRRs greater than 1, but these differences did not reach statistical significance (perinatally acquired HIV: adjusted risk ratio [aRR], 0.46; 95% CI, 0.21-1.02; race other than Black: aRR, 0.53; 95% CI, 0.26-1.08; multiparous: aRR, 0.59; 95% CI, 0.35-1.00; age 24-29 years: aRR, 2.03; 95% CI, 0.92-4.48). Conclusions and Relevance: In this diverse, multicenter cohort of pregnant PLHIV, receipt of recommended vaccinations was low. Identifying and addressing barriers to vaccination receipt is urgently needed for pregnant people with HIV.

Nurse-Initiated Protocol to Improve Timely Antibiotic Administration in Pediatric Open Fractures.

BACKGROUND: Early administration of antibiotics in the presence of open fractures is critical in reducing infections and later complications. Current guidelines recommend administering antibiotics within 60 min of patient arrival to the emergency department, yet trauma centers often struggle to meet this metric. OBJECTIVES: This study aims to evaluate the impact of a nurse-initiated evidence-based treatment protocol on the timeliness of antibiotic administration in pediatric patients with open fractures. METHODS: A retrospective pre-post study of patients who met the National Trauma Data Standard registry inclusion criteria for open fractures of long bones, amputations, or lawn mower injuries was performed at a Midwestern United States Level II pediatric trauma center. The time of patient arrival and time of antibiotic administration from preimplementation (2015-2020) to postimplementation (2021-2022) of the protocol were compared. Patients transferred in who received antibiotics at an outside facility were excluded. RESULTS: A total of N = 73 participants met the study inclusion criteria, of which n = 41 were in the preimplementation group and n = 32 were in the postimplementation group. Patients receiving antibiotics within 60 min of arrival increased from n = 24/41 (58.5%) preimplementation to n = 26/32 (84.4%) postimplementation (p< .05). CONCLUSIONS: Our study demonstrates that initiating evidence-based treatment orders from triage helped decrease the time from arrival to time of antibiotic administration in patients with open fractures. We sustained improvement for 24 months after the implementation of our intervention.

Imaging Assessment of Radiation Therapy-Related Normal Tissue Injury in Children: A PENTEC Visionary Statement.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium has made significant contributions to understanding and mitigating the adverse effects of childhood cancer therapy. This review addresses the role of diagnostic imaging in detecting, screening, and comprehending radiation therapy-related late effects in children, drawing insights from individual organ-specific PENTEC reports. We further explore how the development of imaging biomarkers for key organ systems, alongside technical advancements and translational imaging approaches, may enhance the systematic application of imaging evaluations in childhood cancer survivors. Moreover, the review critically examines knowledge gaps and identifies technical and practical limitations of existing imaging modalities in the pediatric population. Addressing these challenges may expand access to, minimize the risk of, and optimize the real-world application of, new imaging techniques. The PENTEC team envisions this document as a roadmap for the future development of imaging strategies in childhood cancer survivors, with the overarching goal of improving long-term health outcomes and quality of life for this vulnerable population.

A Review of Socioeconomic Disparities in Submucous Cleft Diagnosis and Outcomes.

Submucous cleft palate (SMCP) is a common congenital anomaly characterized by a diastasis of the levator veli palitini muscle. The subtlety of SMCP on physical examination can contribute to diagnostic delays. This study aims to analyze the factors contributing to delays in care and subsequent postoperative outcomes in patients with SMCP. All patients with surgical indications for SMCP who underwent palatoplasty at an urban academic children's hospital were included. Patient socioeconomic characteristics, medical history, and postoperative outcomes were collected. Patients were compared based on insurance type and government assistance utilization. Statistical analyses including independent t-test, Wilcoxon ranked sum test, χ2 analyses, Fisher's exact test, and stepwise logistic regression were performed. Among the 105 patients with SMCP, 69.5% (n=73) had public insurance and 30.5% (n=32) private. Patients with public insurance were diagnosed later (5.5±4.6 versus 2.6±2.4 years old; p<0.001) and underwent palatoplasty later (7.3±4.1 versus 4.4±3.4 years old; p<0.001) than those with private insurance. Patients receiving government assistance experienced higher rates of post-surgical persistent velopharyngeal insufficiency (74.5% versus 44.8%; p=0.006). The authors' results suggest a disparity in the recognition and treatment of surgical SMCP. Hence, financially vulnerable populations may experience an increased risk of inferior speech outcomes and subsequent therapies and procedures.

The Windshield Wiper Sign Is an Instability-Related Osteochondral Defect of the Anterolateral Femoral Head.

PURPOSE: To investigate a radiographic sign believed to be indicative of hip instability and acetabular suction seal disruption in the native hip, coined the "windshield wiper" (WSW) sign. METHODS: A retrospective review was performed for patients who underwent periacetabular osteotomy (PAO) with the senior author between March 2021 and September 2023. A WSW sign was identified on plain films as a concave or flat osteochondral defect on the anterolateral femoral head extending medial to the head-neck junction with resultant loss of femoral head sphericity in the native hip. Every patient underwent a standardized series of radiographs, as well as computed tomography and magnetic resonance imaging. All patients underwent arthroscopy before PAO to address intra-articular pathology and other indicated procedures. The osteochondral defect and resultant suction seal disruption were verified during arthroscopy. These patients were then compared with a control group of arthroscopically treated hips without hip instability. RESULTS: Of 250 patients reviewed, a total of 19 hips in 17 patients (prevalence of 7.6%) demonstrated radiographic evidence of the WSW sign. All patients with a WSW sign presented with symptomatic clinical hip instability requiring a PAO. The mean patient age was 31.2 years, with a mean lateral center-edge angle (LCEA) of 14.3°. There were 13 hips (68.4%) with dysplasia, 4 (21.1%) with borderline dysplasia, and 2 (10.5%) with a normal LCEA. All patients with a WSW sign and LCEA ≥ 20° displayed significant femoral antetorsion abnormalities. All arthroscopic videos and images demonstrated a compromised suction seal. Of the 50 control group hips reviewed, the WSW sign was not identified. CONCLUSIONS: The WSW sign is an uncommon radiographic finding in patients with hip instability. When identified, it can be predictive of substantial instability, especially in cases which are otherwise considered borderline dysplasia or normal based on LCEA. LEVEL OF EVIDENCE: Level III, retrospective comparative case control study.

Activating point mutations in the MET kinase domain represent a unique molecular subset of lung cancer and other malignancies targetable with MET inhibitors.

Activating point mutations in the MET tyrosine kinase domain (TKD) are oncogenic in a subset of papillary renal cell carcinomas (PRCC). Here, using comprehensive genomic profiling among >600,000 patients, we identify activating MET TKD point mutations as putative oncogenic driver across diverse cancers, with a frequency of ~0.5%. The most common mutations in the MET TKD defined as oncogenic or likely oncogenic according to OncoKB resulted in amino acid substitutions at positions H1094, L1195, F1200, D1228, Y1230, M1250, and others. Preclinical modeling of these alterations confirmed their oncogenic potential, and also demonstrated differential patterns of sensitivity to type I and type II MET inhibitors. Two patients with metastatic lung adenocarcinoma harboring MET TKD mutations (H1094Y, F1200I) and no other known oncogenic drivers achieved confirmed partial responses to a type I MET inhibitor. Activating MET TKD mutations occur in multiple malignancies and may confer clinical sensitivity to currently available MET inhibitors.

Geographic Accessibility and Completion of Initial Low-Dose CT-Based Lung Cancer Screening in an Urban Safety-Net Population.

BACKGROUND: Recent modifications to low-dose CT (LDCT)-based lung cancer screening guidelines increase the number of eligible individuals, particularly among racial and ethnic minorities. Because these populations disproportionately live in metropolitan areas, we analyzed the association between travel time and initial LDCT completion within an integrated, urban safety-net health care system. METHODS: Using Esri's StreetMap Premium, OpenStreetMap, and the r5r package in R, we determined projected private vehicle and public transportation travel times between patient residence and the screening facility for LDCT ordered in March 2017 through December 2022 at Parkland Memorial Hospital in Dallas, Texas. We characterized associations between travel time and LDCT completion in univariable and multivariable analyses. We tested these associations in a simulation of 10,000 permutations of private vehicle and public transportation distribution. RESULTS: A total of 2,287 patients were included in the analysis, of whom 1,553 (68%) completed the initial ordered LDCT. Mean age was 63 years, and 73% were underrepresented minorities. Median travel time from patient residence to the LDCT screening facility was 17 minutes by private vehicle and 67 minutes by public transportation. There was a small difference in travel time to the LDCT screening facility by public transportation for patients who completed LDCT versus those who did not (67 vs 66 min, respectively; P=.04) but no difference in travel time by private vehicle for these patients (17 min for both; P=.67). In multivariable analysis, LDCT completion was not associated with projected travel time to the LDCT facility by private vehicle (odds ratio, 1.01; 95% CI, 0.82-1.25) or public transportation (odds ratio, 1.14; 95% CI, 0.89-1.44). Similar results were noted across travel-type permutations. Black individuals were 29% less likely to complete LDCT screening compared with White individuals. CONCLUSIONS: In an urban population comprising predominantly underrepresented minorities, projected travel time is not associated with initial LDCT completion in an integrated health care system. Other reasons for differences in LDCT completion warrant investigation.

The role of uncertainty in regulating associative change.

Rescorla (2000, 2001) interpreted his compound test results to show that both common and individual error terms regulate associative change such that the element of a conditioned compound with the greater prediction error undergoes greater associative change than the one with the smaller prediction error. However, it has recently been suggested that uncertainty, not prediction error, is the primary determinant of associative change in people (Spicer et al., 2020, 2022). The current experiments use the compound test in a continuous outcome allergist task to assess the role of uncertainty in associative change, using two different manipulations of uncertainty: outcome uncertainty (where participants are uncertain of the level of the outcome on a particular trial) and causal uncertainty (where participants are uncertain of the contribution of the cue to the level of the outcome). We replicate Rescorla's compound test results in the case of both associative gains (Experiment 1) and associative losses (Experiment 3) and then provide evidence for greater change to more uncertain cues in the case of associative gains (Experiments 2 and 4), but not associative losses (Experiments 3 and 5). We discuss the findings in terms of the notion of theory protection advanced by Spicer et al., and other ways of thinking about the compound test procedure, such as that proposed by Holmes et al. (2019). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Arthroscopic Femoral Head Allograft With Proximal Femoral/Periacetabular Osteotomies for Sequelae of Perthes: A Case Report.

CASE: We describe the unique case of a 20-year-old man with a history of Legg-Calve-Perthes disease, hip dysplasia, and osteochondral fragmentation of the medial femoral head. We performed arthroscopic femoroplasty and femoral head allografting, followed by a valgus-producing derotational femoral osteotomy (DFO) and periacetabular osteotomy (PAO). At 1-year follow-up, the patient achieved osseous union and complete femoral head healing with return to his active hobbies. CONCLUSION: We describe the successful utilization of arthroscopic allografting for medial femoral head osteochondral fragmentation. To our knowledge, this is the first report on femoral head arthroscopic allografting before DFO and PAO.

Rapid spectrophotometric detection for optimized production of landomycins and characterization of their therapeutic potential.

Microbial-derived natural products remain a major source of structurally diverse bioactive compounds and chemical scaffolds that have the potential as new therapeutics to target drug-resistant pathogens and cancers. In particular, genome mining has revealed the vast number of cryptic or low-yield biosynthetic gene clusters in the genus Streptomyces. However, low natural product yields-improvements to which have been hindered by the lack of high throughput methods-have slowed the discovery and development of many potential therapeutics. Here, we describe our efforts to improve yields of landomycins-angucycline family polyketides under investigation as cancer therapeutics-by a genetically modified Streptomyces cyanogenus 136. After simplifying the extraction process from S. cyanogenus cultures, we identified a wavelength at which the major landomycin products are absorbed in culture extracts, which we used to systematically explore culture medium compositions to improve total landomycin titers. Through correlational analysis, we simplified the culture optimization process by identifying an alternative wavelength at which culture supernatants absorb yet is representative of total landomycin titers. Using the subsequently improved sample throughput, we explored landomycin production during the culturing process to further increase landomycin yield and reduce culture time. Testing the antimicrobial activity of the isolated landomycins, we report broad inhibition of Gram-positive bacteria, inhibition of fungi by landomycinone, and broad landomycin resistance by Gram-negative bacteria that is likely mediated by the exclusion of landomycins by the bacterial membrane. Finally, the anticancer activity of the isolated landomycins against A549 lung carcinoma cells agrees with previous reports on other cell lines that glycan chain length correlates with activity. Given the prevalence of natural products produced by Streptomyces, as well as the light-absorbing moieties common to bioactive natural products and their metabolic precursors, our method is relevant to improving the yields of other natural products of interest.

Altered transcriptomic immune responses of maintenance hemodialysis patients to the COVID-19 mRNA vaccine.

Background: End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines. Methods: The immune response to the COVID-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and 7 d after the second dose (V2D7) using anti-spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified 6 mo after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response. Results: Transcriptomic analyses demonstrated differing time courses of immune responses, with prolonged myeloid cell activity in HD at 1 wk after the first vaccination dose. HD also demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p<0.05). Anti-spike IgG remained elevated above baseline at 6 mo in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development. Conclusions: Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance HD subjects comparable to healthy controls and identify transcriptomic and clinical predictors of anti-spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of ESRD. Funding: F30HD102093, F30HL151182, T32HL144909, R01HL138628. This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003.

Clinical Characteristics and Surgical Outcomes of Patients Undergoing Pars Plana Vitrectomy for Proliferative Diabetic Retinopathy.

OBJECTIVE: To evaluate clinical characteristics impacting surgical outcomes of patients undergoing pars plana vitrectomy (PPV) for complications of proliferative diabetic retinopathy (PDR). DESIGN: Retrospective consecutive observational case series of patients at a large county hospital in Dallas, Texas, from 2014 to 2019. SUBJECTS: Seven hundred thirty-two patients (933 eyes) undergoing PPV for PDR complications. METHODS: Collected data included demographics, surgical indication, adjuvant therapies, intraoperative course, complications, and best corrected visual acuity (BCVA). Patients with < 6 months of follow-up were excluded. Best corrected visual acuity was converted to logarithm of the minimum angle of resolution for analysis. Statistics performed included t test, analysis of variance, and multivariate analyses. MAIN OUTCOME MEASURES: Postoperative BCVA, primary anatomic success rate, and postoperative complications. RESULTS: Three hundred ninety-three patients were male (509 eyes; 54.5%) with an average age of 52 years. Postoperative BCVA at 6 months was significantly different among surgical indications: 0.79 versus 0.77 versus 1.20 (P < 0.0001) for vitreous hemorrhage (VH), vitreomacular interface abnormalities, and tractional retinal detachment (TRD), respectively. Adjuvant preoperative therapy with panretinal photocoagulation (PRP) versus no PRP (0.95 vs. 1.25; P < 0.001) and insulin versus no insulin (0.99 vs. 1.17; P < 0.01) were associated with improved vision. Iatrogenic breaks were associated with decreased postoperative vision (1.40 vs. 0.88; P < 0.001). The primary anatomic success rate for TRD was 85% (495 eyes). Combined TRD/RRD (tractional and rhegmatogenous retinal detachment) was associated with a lower success rate compared with macula-on/macula-off TRD, with odds ratios of 0.36, 0.46, and 0.53, respectively. Patients experiencing recurrent detachment postsurgery had worse preoperative visual acuity (VA) (1.93 vs. 1.63; P < 0.01) and were younger (47.6 vs. 50.0; P = 0.02). Postoperative complications occurred in 699 eyes (75%), with VH (498 eyes, 53%), cataract (465, 50%), and elevated intraocular pressure (149, 16%) being the most common. Two hundred thirty-six eyes (25%) required a second PPV operation. Endophthalmitis (1 eye; <1%) and choroidal detachment (5 eyes; <1%) were rare. CONCLUSIONS: In this retrospective series analyzing surgical outcomes among patients with complications from PDR, vitrectomy led to improved vision on average, with a meaningful proportion of patients receiving additional surgical intervention. Surgical indication, presenting VA, age, and adjuvant therapies appeared to impact outcomes. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A Single Institution 19 Year Comparison of Furlow and Straight Line Palatoplasty Techniques in Bilateral Cleft Lip and Palate.

OBJECTIVE: This study aims to compare patients' speech correcting surgery and fistula rates between the Furlow and Straight Line (SLR) palatoplasty techniques when combined with greater palatine flaps for complete bilateral cleft lip and palate (BCLP) repair. DESIGN: This was a single-center IRB approved retrospective cohort study. SETTING: This study took place at an urban tertiary academic center. PATIENTS, PARTICIPANTS: All patients with BCLP anomalies that underwent repair between January 2003 and August 2022 were included. Patients with index operations at an outside institution or incomplete medical charting were excluded. INTERVENTIONS: A total of 1552 patients underwent palatoplasty during the study period. Of these, 192 (12.4%) met inclusion criteria with a diagnosis of BCLP. MAIN OUTCOME MEASURES: Primary outcomes of this study included rate of fistula and incidence of speech correcting surgery. Secondary outcomes included rate of surgical fistula repair. RESULTS: One hundred patients underwent SLR (52.1%) and 92 Furlow repair (47.9%). There was no significant difference in fistula rates between the SLR and Furlow repair cohorts (20.7% vs. 15.0%; p = 0.403). However, SLR was associated with lower rates of speech correcting surgery when compared to the Furlow repair (12.5% vs. 29.6%; p = 0.011). CONCLUSIONS: This study compares the effect of Furlow and SLR on speech outcomes and fistula rates in patients with BCLP. Our findings suggest that SLR resulted in an almost three times lower rate of velopharyngeal dysfunction requiring surgical intervention in patients with BCLP, while fistula rates remained similar.

Dynamic changes in perivascular space morphology predict signs of spaceflight-associated neuro-ocular syndrome in bed rest.

During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Association of Timely Comprehensive Genomic Profiling With Precision Oncology Treatment Use and Patient Outcomes in Advanced Non-Small-Cell Lung Cancer.

PURPOSE: Timely biomarker testing remains out of reach for many patients with advanced non-small-cell lung cancer (aNSCLC). Here, we studied the quality-of-care implications of closing the gap in timely receipt of comprehensive genomic profiling (CGP) to inform first-line (1L) decisions. METHODS: Using a real-world clinicogenomic database, we studied testing and 1L treatment patterns in aNSCLC after the approval of pembrolizumab in combination with pemetrexed and carboplatin (May 10, 2017). To estimate the association of timely CGP results with therapy selection and patient outcomes, we identified patients with no previous genomic testing beyond PD-L1 immunohistochemistry and dichotomized patients by whether CGP results were available before or after 1L therapy initiation. RESULTS: In total, 2,694 patients were included in the 1L therapy decision impact assessment. Timely CGP increased matched targeted therapy use by 14 percentage points (17% with CGP v 2.8% without) and precision immune checkpoint inhibitor (ICPI) use by 14 percentage points (18% with CGP v 3.9% without). Receipt of timely CGP resulted in an estimated 31 percentage point decrease in ICPI use among ALK/EGFR/RET/ROS1-positive patients at an expected per-patient reduction in ineffective ICPI therapy cost of $13,659.37 with timely CGP to inform 1L treatment selection. Patient benefit of CGP extended to real-world time to therapy discontinuation (median time to therapy discontinuation: 3.9 v 10 months [hazard ratio, HR, 0.54 [95% CI, 0.42 to 0.70]; P = 1.9E-06; adjusted hazard ratio [aHR], 0.50 [95% CI, 0.38 to 0.67]; P = 2.0E-06) in 1L driver-positive patients. This effect was not significant for real-world overall survival (median overall survival: 32 v 29 months [HR, 1.2 [95% CI, 0.84 to 1.67]; P = .33; aHR, 1.4 [95% CI, 0.92 to 1.99]; P = .12). CONCLUSION: Timely CGP is associated with the quality of patient care as measured by 1L matched targeted therapy use, time to therapy discontinuation, and avoidance of ineffective, costly ICPIs.