Immunomethylomic profiles of long-term head and neck squamous cell carcinoma survivors on immune checkpoint inhibitors.

Aim: This study addresses the challenge of predicting the response of head and neck squamous cell carcinoma (HNSCC) patients to immunotherapy. Methods: Using DNA methylation cytometry, we analyzed the immune profiles of six HNSCC patients who showed a positive response to immunotherapy over a year without disease progression. Results: There was an initial increase in CD8 T memory cells and natural killer cells during the first four cycles of immunotherapy, which then returned to baseline levels after a year. Baseline CD8 T cell levels were lower in HNSCC immunotherapy responders but became similar to those in healthy subjects after immunotherapy. Conclusion: These findings suggest that monitoring fluctuations in immune profiles could potentially identify biomarkers for immunotherapy response in HNSCC patients.

[Box: see text].

Major Psychiatric Disorders, Substance Use Behaviors, and Longevity.

Importance: Observational studies suggest that major psychiatric disorders and substance use behaviors reduce longevity, making it difficult to disentangle their relationships with aging-related outcomes. Objective: To evaluate the associations between the genetic liabilities for major psychiatric disorders, substance use behaviors (smoking and alcohol consumption), and longevity. Design, Settings, and Participants: This 2-sample mendelian randomization (MR) study assessed associations between psychiatric disorders, substance use behaviors, and longevity using single-variable and multivariable models. Multiomics analyses were performed elucidating transcriptomic underpinnings of the MR associations and identifying potential proteomic therapeutic targets. This study sourced summary-level genome-wide association study (GWAS) data, gene expression, and proteomic data from cohorts of European ancestry. Analyses were performed from May 2022 to November 2023. Exposures: Genetic susceptibility for major depression (n = 500 199), bipolar disorder (n = 413 466), schizophrenia (n = 127 906), problematic alcohol use (n = 435 563), weekly alcohol consumption (n = 666 978), and lifetime smoking index (n = 462 690). Main Outcomes and Measures: The main outcome encompassed aspects of health span, lifespan, and exceptional longevity. Additional outcomes were epigenetic age acceleration (EAA) clocks. Results: Findings from multivariable MR models simultaneously assessing psychiatric disorders and substance use behaviorsm suggest a negative association between smoking and longevity in cohorts of European ancestry (n = 709 709; 431 503 [60.8%] female; ß, -0.33; 95% CI, -0.38 to -0.28; P = 4.59 × 10-34) and with increased EAA (n = 34 449; 18 017 [52.3%] female; eg, PhenoAge: ß, 1.76; 95% CI, 0.72 to 2.79; P = 8.83 × 10-4). Transcriptomic imputation and colocalization identified 249 genes associated with smoking, including 36 novel genes not captured by the original smoking GWAS. Enriched pathways included chromatin remodeling and telomere assembly and maintenance. The transcriptome-wide signature of smoking was inversely associated with longevity, and estimates of individual smoking-associated genes, eg, XRCC3 and PRMT6, aligned with the smoking-longevity MR analyses, suggesting underlying transcriptomic mediators. Cis-instrument MR prioritized brain proteins associated with smoking behavior, including LY6H (ß, 0.02; 95% CI, 0.01 to 0.03; P = 2.37 × 10-6) and RIT2 (ß, 0.02; 95% CI, 0.01 to 0.03; P = 1.05 × 10-5), which had favorable adverse-effect profiles across 367 traits evaluated in phenome-wide MR. Conclusions: The findings suggest that the genetic liability of smoking, but not of psychiatric disorders, is associated with longevity. Transcriptomic associations offer insights into smoking-related pathways, and identified proteomic targets may inform therapeutic development for smoking cessation strategies.

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction.

We describe the use of bismuth(III) triflate as an efficient and environmentally friendly catalyst for the Nazarov reaction of aryl vinyl ketones, leading to the synthesis of 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones. By changing the temperature and reaction time, it was possible to modulate the reactivity, allowing the synthesis of two distinct product classes (3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells.

Anticonvulsant and anxiolytic-like potential of the essential oil from the Ocimum basilicum Linn leaves and its major constituent estragole on adult zebrafish (Danio rerio).

The Ocimum species present active compounds with the potential to develop drugs for treating chronic disease conditions, such as anxiety and seizures. The present study aims to investigate the anticonvulsant and anxiolytic-like effect of the essential oil from O. basilicum Linn (OEFOb) leaves and its major constituent estragole (ES) in vivo on adult zebrafish (aZF) and in silico. The aZF were treated with OEFOb or ES or vehicle and submitted to the tests of toxicity, open-field, anxiety, and convulsion and validated the interactions of the estragole on the involvement of GABAergic and serotonergic receptors by molecular docking assay. The results showed that the oral administration of OEFOb and ES did not have a toxic effect on the aZF and showed anxiolytic-like effects with the involvement of GABAA, 5-HT1, 5-HT2A/2C and 5-HT3A/3B as well on anxiety induced by alcohol withdrawal. The OEFOb and ES showed anticonvulsant potential attenuating the seizures induced by pentylenetetrazole (PTZ) by modulation of the GABAA system. Both anxiolytic and anticonvulsant effects were corroborated by the potential of the interaction of ES by in silico assay. These study samples demonstrate the pharmacological evidence and potential for using these compounds to develop new anxiolytic and anticonvulsant drugs.

Design of a Lead-Like Cysteine-Targeting Covalent Library and the Identification of Hits to Cys55 of Bfl-1.

Covalent hit identification is a viable approach to identify chemical starting points against difficult-to-drug targets. While most researchers screen libraries of <2k electrophilic fragments, focusing on lead-like compounds can be advantageous in terms of finding hits with improved affinity and with a better chance of identifying cryptic pockets. However, due to the increased molecular complexity, larger numbers of compounds (>10k) are desirable to ensure adequate coverage of chemical space. Herein, the approach taken to build a library of 12k covalent lead-like compounds is reported, utilizing legacy compounds, robust library chemistry, and acquisitions. The lead-like covalent library was screened against the antiapoptotic protein Bfl-1, and six promising hits that displaced the BIM peptide from the PPI interface were identified. Intriguingly, X-ray crystallography of lead-like compound 8 showed that it binds to a previously unobserved conformation of the Bfl-1 protein and is an ideal starting point for the optimization of Bfl-1 inhibitors.

Predisposing risk factors for cleft lip and palate in an Amazonian population by focusing on nutritional factors: A case-control study.

BACKGROUND: Orofacial clefts (OFC) are the most common congenital malformation of the craniofacial skeleton. Attempts have been made to correlate the components of maternal diet as triggers for the development or prevention of OFC. OBJECTIVE: To analyze nutritional status as a predictive factor for the development of cleft lip and palate in an Amazonian population. METHODS: A total of 152 mothers within 3 months of delivery were interviewed for comparison: 51 mothers of children with nonsyndromic cleft lip and palate (CLP) (study group) and 101 mothers of children without OFC (control group). A food frequency questionnaire was used to assess maternal nutrition and to analyze the influence of macro- and micronutrients on the possible predisposition or protection for CLP. RESULTS: The study group showed higher percentage of lipid intake than did the control group (p = 0.01). Among the participants with no family history of OFC, the study group had a higher percentage of lipid intake (p = 0.002) and lower vegetable intake (p = 0.037). Maternal micronutrient intake among the participants with a positive family history was lower in the study group for vitamins B2 (p = 0.03), B5 (p = 0.036), E (p = 0.03), and folate (p = 0.022). CONCLUSIONS: Nutritional analysis indicated that higher maternal lipid intake increased the likelihood of having offsprings with nonsyndromic CLP. Moreover, families with a history of OFC and low maternal folate intake showed heightened risk of nonsyndromic CLP in their offsprings.

Impacts of elevated temperature and vapour pressure deficit on leaf gas exchange and plant growth across six tropical rainforest tree species.

Elevated air temperature (Tair) and vapour pressure deficit (VPDair) significantly influence plant functioning, yet their relative impacts are difficult to disentangle. We examined the effects of elevated Tair (+6°C) and VPDair (+0.7 kPa) on the growth and physiology of six tropical tree species. Saplings were grown under well-watered conditions in climate-controlled glasshouses for 6 months under three treatments: (1) low Tair and low VPDair, (2) high Tair and low VPDair, and (3) high Tair and high VPDair. To assess acclimation, physiological parameters were measured at a set temperature. Warm-grown plants grown under elevated VPDair had significantly reduced stomatal conductance and increased instantaneous water use efficiency compared to plants grown under low VPDair. Photosynthetic biochemistry and thermal tolerance (Tcrit) were unaffected by VPDair, but elevated Tair caused Jmax25 to decrease and Tcrit to increase. Sapling biomass accumulation for all species responded positively to an increase in Tair, but elevated VPDair limited growth. This study shows that stomatal limitation caused by even moderate increases in VPDair can decrease productivity and growth rates in tropical species independently from Tair and has important implications for modelling the impacts of climate change on tropical forests.

Pediatric Facial Fractures: Demographics, Injury Patterns, and Associated Injuries in 3334 Patients.

Pediatric craniofacial fractures are fundamentally distinct from their adult counterparts because of unique injury patterns and effects on future growth. Understanding patterns and injury context informs management and risk mitigation. Previous studies include only inpatients, operative patients, or are specialty-specific. In contrast, our study presents a comprehensive assessment of all pediatric facial fracture patients seen at a single institution. Patients under 18 years old who were evaluated for facial fractures at a level I pediatric trauma center between 2006 and 2021 were reviewed. Subanalysis was performed for groups defined by age. Variables studied included demographics, etiology, fracture pattern, associated injuries, management, and outcomes. Three thousand thirty-four patients were included. Mean age at presentation was 11.5 to 4.9 years. The majority were Caucasian (82.6%) and male (68.4%). Sports were the leading cause of injury in older patients (42.2% of patients over 12 y), compared with activities of daily living in patients under 6 years (45.5%). Thirty-two percent of patients were hospitalized, 6.0% required ICU care, and 48.4% required surgery. Frequency of ICU admission decreased with age (P<0.001), whereas operative intervention increased with age (P<0.001). Zygomaticomaxillary complex (P=0.002) and nasal fractures (P<0.001) were common in older patients, whereas younger patients experienced more skull (P<0.001) and orbital fractures (P<0.001). The most associated injuries were soft tissue (55.7%) and neurologic (23.6%). This large-scale study provides updated characterization of craniofacial fractures in the pediatric population, providing a necessary framework for future studies on outcomes assessments and preventative care.

The incidence of subsequent hip arthroscopy after rectus-sparing periacetabular osteotomy.

Aims: Periacetabular osteotomy (PAO) is the preferred treatment for symptomatic acetabular dysplasia in adolescents and young adults. There remains a lack of consensus regarding whether intra-articular procedures such as labral repair or improvement of femoral offset should be performed at the time of PAO or addressed subsequent to PAO if symptoms warrant. The purpose was to determine the rate of subsequent hip arthroscopy (HA) in a contemporary cohort of patients, who underwent PAO in isolation without any intra-articular procedures. Methods: From June 2012 to March 2022, 349 rectus-sparing PAOs were performed and followed for a minimum of one year (mean 6.2 years (1 to 11)). The mean age was 24 years (14 to 46) and 88.8% were female (n = 310). Patients were evaluated at final follow-up for patient-reported outcome measures (PROMs). Clinical records were reviewed for complications or subsequent surgery. Radiographs were reviewed for the following acetabular parameters: lateral centre-edge angle, anterior centre-edge angle, acetabular index, and the alpha-angle (AA). Patients were cross-referenced from the two largest hospital systems in our area to determine if subsequent HA was performed. Descriptive statistics were used to analyze risk factors for HA. Results: A total of 16 hips (15 patients; 4.6%) underwent subsequent HA with labral repair and femoral osteochondroplasty, the most common interventions. For those with a minimum of two years of follow-up, 5.3% (n = 14) underwent subsequent HA. No hips underwent total hip arthroplasty and one revision PAO was performed. Overall, 17 hips (4.9%) experienced a complication and 99 (26.9%) underwent hardware removal. All PROMs improved significantly postoperatively. Radiologically, 80% of hips (n = 279) reached the goal for acetabular correction (77% for acetbular index and 93% for LCEA), with no significant differences between those who underwent subsequent HA and those who did not. Conclusion: Rectus-sparing PAO is associated with a low rate of subsequent HA for intra-articular pathology at a mean of 6.2 years' follow-up (1 to 11). Acetabular correction alone may be sufficient as the primary intervention for the majority of patients with symptomatic acetabular dysplasia.

Molecular subtypes of high-grade serous ovarian cancer across racial groups and gene expression platforms.

BACKGROUND: High-grade serous carcinoma (HGSC) gene expression subtypes are associated with differential survival. We characterized HGSC gene expression in Black individuals and considered whether gene expression differences by self-identified race may contribute to poorer HGSC survival among Black versus White individuals. METHODS: We included newly generated RNA-Seq data from Black and White individuals, and array-based genotyping data from four existing studies of White and Japanese individuals. We used K-means clustering, a method with no predefined number of clusters or dataset-specific features, to assign subtypes. Cluster- and dataset-specific gene expression patterns were summarized by moderated t-scores. We compared cluster-specific gene expression patterns across datasets by calculating the correlation between the summarized vectors of moderated t-scores. Following mapping to The Cancer Genome Atlas (TCGA)-derived HGSC subtypes, we used Cox proportional hazards models to estimate subtype-specific survival by dataset. RESULTS: Cluster-specific gene expression was similar across gene expression platforms and racial groups. Comparing the Black population to the White and Japanese populations, the immunoreactive subtype was more common (39% versus 23%-28%) and the differentiated subtype less common (7% versus 22%-31%). Patterns of subtype-specific survival were similar between the Black and White populations with RNA-Seq data; compared to mesenchymal cases, the risk of death was similar for proliferative and differentiated cases and suggestively lower for immunoreactive cases (Black population HR=0.79 [0.55, 1.13], White population HR=0.86 [0.62, 1.19]). CONCLUSIONS: While the prevalence of HGSC subtypes varied by race, subtype-specific survival was similar. IMPACT: HGSC subtypes can be consistently assigned across platforms and self-identified racial groups.

Total Intravenous Anesthesia with Propofol Reduces Discharge Times Compared with Inhaled General Anesthesia in Shoulder Arthroscopy: A Randomized Controlled Trial.

BACKGROUND: Shoulder arthroscopy is commonly performed at ambulatory surgical centers (ASCs) with use of an interscalene block and inhaled general anesthesia (IGA). However, an alternative option known as total intravenous anesthesia with propofol (TIVA-P) has shown promising results in reducing recovery time for other surgeries. The objective of this study was to assess whether there is a clinically meaningful difference in post-anesthesia care unit phase-I (PACU-I) time following shoulder arthroscopy between patients receiving an interscalene block with IGA and those receiving an interscalene block with TIVA-P. METHODS: Patients who underwent shoulder arthroscopy performed by a single surgeon at the ASC of our institution between 2020 and 2023 were enrolled. Enrollment was conducted in blocks, with up to 3 planned interim analyses. After 2 blocks, enrollment was halted because the study arms demonstrated a significant difference in the primary outcome measure, PACU-I time. A total of 96 patients were randomized into the TIVA-P and IGA groups; after patient withdrawals, the groups comprised 42 and 40 patients, respectively. Patients underwent shoulder arthroscopy with use of the anesthesia method corresponding to their assigned group. Pain, satisfaction, antiemetic use, perioperative interventions, surgical time, PACU-II time, postoperative care time, and total time until discharge were recorded and were analyzed with use of chi-square and Mann-Whitney U tests with a significance cutoff of 0.0167 to account for the interim analyses. RESULTS: Across groups, 81.7% of patients were non-Hispanic White and 58.5% were male. Significant differences were observed between the TIVA-P and IGA groups with respect to median PACU-I time (0.0 minutes [interquartile range (IQR), 0.0 to 6.0 minutes] versus 25.5 minutes [IQR, 20.5 to 32.5 minutes]; p < 0.001) and median total time until discharge (135.5 minutes [IQR, 118.5 to 156.8 minutes] versus 148.5 minutes [IQR, 133.8 to 168.8 minutes]; p = 0.0104). The TIVA-P group had a 9.1% quicker discharge time, primarily as a result of bypassing PACU-I (66.7% of patients) and spending 25.5 fewer minutes there overall. The TIVA-P group also had a lower rate of antiemetic use than the IGA group (59.5% versus 92.5% of patients; p = 0.0013). No significant differences were detected between the TIVA-P and IGA groups in terms of median pain improvement (1.0 [IQR, 0.0 to 2.0] versus 1.0 [IQR, 0.0 to 2.0]; p = 0.6734), perioperative interventions (78.6% versus 77.5% of patients, p = 1.0000), or median patient satisfaction (4.0 [IQR, 4.0 to 4.0] versus 4.0 [IQR, 3.8 to 4.0]; p = 0.4148). CONCLUSIONS: TIVA-P showed potential to improve both PACU-I time and the total time until discharge while reducing antiemetic use without impacting pain or satisfaction. TIVA-P thus warrants consideration by orthopaedic surgeons for use in shoulder arthroscopy performed at ASCs. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Discharge to a Skilled Nursing Facility After Hip Fracture Results in Higher Rates of Periprosthetic Joint Infection.

BACKGROUND: Femoral neck fractures (FNFs) in elderly patients are associated with major morbidity and mortality. The influence of postoperative discharge location on recovery and outcomes after arthroplasty for hip fractures is not well understood. METHODS: A multisite retrospective cohort from 9 academic centers identified patients who had FNF treated with hemiarthroplasty or total hip arthroplasty between 2010 and 2019. Patients who had diagnoses of dementia, stroke, age > 80 years, or high energy fracture were excluded. Discharge location was identified, including home-based health services (HHS), inpatient rehabilitation (IPR), or a skilled nursing facility (SNF). Rates of reoperation, periprosthetic joint infection (PJI), and mortality were compared between cohorts. Multivariate logistic regressions were performed, adjusting for age, American Society of Anesthesiologists (ASA) score, body mass index, sex, and tobacco use. Statistical significance was defined as P < .05. RESULTS: A total of 672 patients (315 HHS, 144 IPR, and 213 SNF) were included in this study. The average follow-up was 30 months. The SNF cohort was significantly older (P < .0001) with higher ASA scores (P < .0001) than the HHS cohort. In a logistic regression model adjusting for age, ASA score, and body mass index, the SNF cohort had higher mortality rates than the HHS cohort (P = .0296) and were more likely to have PJI within 90 days (odds ratio = 4.55, 95% confidence interval = 1.40, 4.74) and within 1 year (odds ratio = 3.08, 95% confidence interval = 1.08, 8.78). Time to PJI was significantly shorter in the SNF cohort (SNF 38 versus HHS 231 days, P = .0155). No differences were seen in dislocation or reoperation rates between the SNF and HHS cohorts. No differences were seen in complication rates between the IPR and HHS cohorts. CONCLUSIONS: Discharge to a SNF after arthroplasty for FNF is associated with increased mortality and higher rates of PJI. Hip fracture care pathways that uniformly discharge patients to SNFs may need to be re-evaluated, and surgeons should consider discharge to home with HHS when possible.

Similar Efficacy and Lower Cost Associated With Ceftazidime Compared to Tobramycin Coupled With Vancomycin in Antibiotic Spacers in the Treatment of Periprosthetic Joint Infection.

BACKGROUND: Vancomycin and tobramycin have traditionally been used in antibiotic spacers. In 2020, our institution replaced tobramycin with ceftazidime. We hypothesized that the use of ceftazidime/vancomycin (CV) in antibiotic spacers would not lead to an increase in treatment failure compared to tobramycin/vancomycin (TV). METHODS: From 2014 to 2022, we identified 243 patients who underwent a stage I revision for periprosthetic joint infection. The primary outcome was a recurrent infection requiring antibiotic spacer exchange. We were adequately powered to detect a 10% difference in recurrent infection. Patients who had a prior failed stage I or two-stage revision for infection, acute kidney injury prior to surgery, or end-stage renal disease were excluded. Given no other changes to our spacer constructs, we estimated cost differences attributable to the antibiotic change. Chi-square and t-tests were used to compare the two groups. Multivariable logistic regressions were utilized for the outcomes. RESULTS: The combination of TV was used in 127 patients; CV was used in 116 patients. Within one year of stage I, 9.8% of the TV group had a recurrence of infection versus 7.8% of the CV group (P = .60). By final follow-up, results were similar (12.6 versus 8.6%, respectively, P = .32). Adjusting for potential risk factors did not alter the results. Cost savings for ceftazidime versus tobramycin are estimated to be $68,550 per one hundred patients treated. CONCLUSIONS: Replacing tobramycin with ceftazidime in antibiotic spacers yielded similar periprosthetic joint infection eradication success at a lower cost. While larger studies are warranted to confirm these efficacy and cost-saving results, our data justifies the continued investigation and use of ceftazidime as an alternative to tobramycin in antibiotic spacers.

Dysplastic Hips That Are Too Late for Periacetabular Osteotomy Are Not Too Early for Total Hip Arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is often performed in symptomatic patients who have hip dysplasia and do not qualify for periacetabular osteotomy. The impact of osteoarthritis (OA) severity on postoperative outcomes in dysplasia patients who undergo THA is not well described. We hypothesized that dysplasia patients who have mild OA have slower initial recovery postoperatively but similar one-year patient-reported outcome measures (PROMs) compared to dysplasia patients who have severe OA. METHODS: We performed a retrospective review at a single academic institution over a 6-year period of patients who have dysplasia who underwent THA compared to patients who have primary OA who underwent THA. There were 263 patients who had dysplasia, compared to 1,225 THA patients who did not have dysplasia. Within the dysplasia cohort, we compared PROMs stratified by dysplasia and OA severity. The diagnosis of dysplasia was verified using the radiographic lateral center edge angle. A minimum one-year follow-up was required. The PROMs were collected through one year postoperatively. Logistic and linear regression models were used, adjusting for age, sex, body mass index, and Charlson comorbidity index. RESULTS: No significant differences were found in postoperative PROMs or revision rates (P = .58). When stratified by dysplasia severity, patients who had lower lateral center edge angle had more improvement in physical function scores from preoperative to 2 weeks (P < .01) and higher physical function scores at 2 weeks (P = .03). When stratified by OA severity, patients who had a worse Tönnis score had more improvement in physical function scores from preoperative to 2 weeks (P < .01). Recovery curves in dysplasia patients based on dysplasia and OA severity were not significantly different at 6 weeks, 1 year, and 2 years postoperative. CONCLUSIONS: Patients who had hip dysplasia and mild OA had similar recovery curves compared to those who had severe OA or who did not have dysplasia. We believe that THA is a reasonable surgical intervention for symptomatic dysplasia patients who have mild arthritis and do not qualify for periacetabular osteotomy.

Associations in cell type-specific hydroxymethylation and transcriptional alterations of pediatric central nervous system tumors.

Although intratumoral heterogeneity has been established in pediatric central nervous system tumors, epigenomic alterations at the cell type level have largely remained unresolved. To identify cell type-specific alterations to cytosine modifications in pediatric central nervous system tumors, we utilize a multi-omic approach that integrated bulk DNA cytosine modification data (methylation and hydroxymethylation) with both bulk and single-cell RNA-sequencing data. We demonstrate a large reduction in the scope of significantly differentially modified cytosines in tumors when accounting for tumor cell type composition. In the progenitor-like cell types of tumors, we identify a preponderance differential Cytosine-phosphate-Guanine site hydroxymethylation rather than methylation. Genes with differential hydroxymethylation, like histone deacetylase 4 and insulin-like growth factor 1 receptor, are associated with cell type-specific changes in gene expression in tumors. Our results highlight the importance of epigenomic alterations in the progenitor-like cell types and its role in cell type-specific transcriptional regulation in pediatric central nervous system tumors.

Redefining treatment expectations: exploring mid- and long-term outcomes of venous sinus stenting in idiopathic intracranial hypertension.

BACKGROUND: Venous sinus stenting (VSS) is recognized as a safe and effective intervention for medically-refractory idiopathic intracranial hypertension (IIH). However, its long-term efficacy remains uncertain. METHODS: This retrospective review analyzed a single-center database of adult patients with severe, medically-refractory IIH, who underwent VSS and had minimum 3-month follow-up (FU). Patients were divided into three groups based on post-stenting symptom trajectories: group 1 (sustained improvement without relapse), group 2 (temporary improvement with relapse), and group 3 (no improvement). RESULTS: Of 178 patients undergoing VSS, the majority were female (94%), with a median opening pressure (OP) of 31 cm H2O and trans-stenosis gradient of 14 mm Hg. Of these, 153 (86%) received transverse sinus (TS) stenting, and 19 (11%) underwent concurrent TS and superior sagittal sinus stenting. At a mean FU of 166 days, 53 patients (30%) showed long-term improvement without relapse (group 1). Symptomatic recurrence was noted in 101 patients (57%; group 2) within a mean FU of 390 days. Despite recurrent headache and tinnitus, the average OP reduction was 9.6 cm H2O on repeat lumbar puncture, with 75% showing papilledema improvement or resolution post-VSS. Only 17% required further surgical intervention. CONCLUSIONS: The most common clinical outcome post-VSS in IIH patients is initial symptomatic improvement followed by symptom recurrence in about 60% at a mean of 274 days, despite a consistent intracranial pressure reduction. These findings can guide physicians in setting realistic expectations with patients regarding VSS outcomes.

Social media analysis of pain outcomes following targeted muscle reinnervation.

AIM: Targeted muscle reinnervation (TMR) was developed to improve myoelectric prosthesis control for amputees; however, it has become an area of interest in pain modulation. Evidences indicate that this procedure alleviates chronic pain in amputees. The primary objective of this study was to use social media analysis to understand patients' post-operative pain, satisfaction, and recovery time after TMR. METHODS: Data were collected from one Facebook group via posts and comments referencing TMR. Posts published between January 1, 2020, and March 24, 2023 were analyzed. Data collected included pain prior to surgery, pain in immediate post-op period, and change in pain after surgery. RESULTS: Forty-three individuals commented on their TMR experience. Among them, 31 had favorable surgical outcomes, 7 felt that the surgery worsened their pain or there was no significant change in their pain levels, and 5 commented during the initial post-operative period. Twenty-four patients described their pain in the immediate post-operative period and all patients said that the post-operative pain was worse than chronic pain. Among the 28 authors who commented on overall reduction in chronic pain, 24 reported that TMR reduced their pain, whereas 4 reported no change or worsened pain. CONCLUSIONS: The number of patients (24) who reported improvement in chronic pain aligns with the results in current literature suggesting that TMR is a viable treatment option for pain management. With the current medical management of similar conditions, up to 80% of patients remain unsatisfied with pain management. This analysis supports the evidence that TMR is an effective treatment for patients experiencing post-amputation pain.

Risk Factors for Return to the Emergency Department and Readmission After Same-Day Discharge Total Joint Arthroplasty.

BACKGROUND: Same-day discharge (SDD) after total joint arthroplasty (TJA) is safe and cost effective. However, benefits may be offset by the potential cost of emergency department (ED) visits and readmissions. We identified risk factors for return to the ED and readmission in patients who underwent SDD and inpatient (IP) stays after TJA. METHODS: We performed a retrospective review of patients who underwent primary TJA at an academic institution over the course of one year. There were 1,708 consecutive TJAs (721 THA [total hip arthroplasty] and 987 TKA [total knee arthroplasty]) included. A SDD occurred after 1,199 (70%) TJAs, 523 THAs, and 676 TKAs. We compared the demographics and comorbidities of patients who have SDD or IP who stayed following TJA. We documented rates of return to the ED or readmission within 90 days of surgery. Cohorts were compared using the Student's t-test or Chi-square test. Significant findings were those with P value < .05. RESULTS: The SDD cohort had a significantly higher rate of young, non-White men who had a lower body mass index and fewer comorbidities than the IP cohort. Rates of return to ED and readmission were similar between SDD and IP cohorts after TJA and similar between THA and TKA. Factors that significantly influenced return to ED included a higher American Society of Anaesthesiologists score (SDD, IP), a higher Charlson Comorbidity Index score (SDD, IP), a lower body mass index (IP), and a psychological diagnosis (SDD, IP). Factors that significantly influenced readmission rates included a higher American Society of Anaesthesiologists score (SDD), older age (SDD), and psychological diagnosis (SDD, IP). CONCLUSIONS: Patients who discharged the same day after primary TJA have similar rates of return to the ED and readmission as those admitted as an IP. Patients who had a psychological diagnosis, and particularly a diagnosis of depression, are at higher risk for return to the ED and readmission after primary TJA, regardless of discharge the same-day or IP admission. Improved measures that attempt to further treat and optimize this patient population could reduce unnecessary postoperative ED visits.

In vivo evaluation of a polyester and fiberglass composite intramedullary nail for femoral osteosynthesis in calves.

The objective of this study was to test a composite of polyester resin and fiberglass in the form of an intramedullary nail for osteosynthesis of femoral fractures in calves. The methodology was established based on a previous study that used a bovine femur finite element model to simulate fractures, which were then stabilized by the same nails as proposed in this study. General anesthesia was induced in six calves followed by fracture creation via an oblique incision in the middle third of the femoral diaphysis, and osteosynthesis was immediately performed by retrograde insertion of the composite nail. Locking was achieved by drilling the bone and nail without using a jig and introducing two stainless steel screws proximal and two distal to the fracture line. Five of the six calves achieved complete fracture healing after 60 days. No signs of incompatibility or toxicity of the composite were observed. However, limitations were observed during the surgery, such as difficulty in drilling the nail and trimming the remainder portion of the nail that extended beyond the length of the bone. Small fragments produced by these maneuvers were considered irritating to soft tissues during the postoperative period. It was also found that small cracks in the nail tended to propagate in the form of longitudinal fractures. In conclusion, an intramedullary nail made of polyester resin and fiberglass (a low-cost and easy-to-acquire material) was considered biocompatible and capable of allowing bone healing of femoral fractures in young cattle. However, the development of solutions for the reported limitations is crucial prior to recommending the proposed composite for clinical use.