The impact of adenotonsillectomy on healthcare utilization in children with obstructive sleep apnea: Experience of an integrated medical model.

BACKGROUND AND OBJECTIVES: Studies suggest that children with obstructive sleep apnea (OSA) have increased healthcare utilization patterns in comparison to matched controls. However, the effect of adenotonsillectomy (AT) on utilization patterns in these children is poorly understood. Additionally, no previous studies have compared the effect of AT on healthcare utilization patterns across different OSA severity groups. The aim of this retrospective cohort study is to assess the effects of surgical treatment on the level of healthcare utilization among children with OSA at a large integrated multicenter healthcare system. METHODS: Retrospective analysis was performed of children aged 3-12 diagnosed with OSA via an attended polysomnogram (PSG) between December 2016 and February 2019. Demographic variables including age (at time of PSG), body mass index (BMI), race, and ethnicity were obtained. Variables for healthcare utilization were assessed for 12 months prior to PSG, and for 12 months after PSG (or after AT, delayed for the first 30 days after surgery to account for surgery-related visits). Healthcare utilization variables assessed included the total number of outpatient visits, inpatient, and emergency department (ED) visits, visits involving diagnostic codes associated with upper respiratory infection (URI), otitis media (OM), and allergic rhinitis (AR), prescription data involving intranasal steroids or leukotriene receptor antagonists (LTRA), and communication data such as secure message load and specialty referrals. Repeated measure linear difference-in-difference (D-I-D) models were used to assess the causal impact of AT on healthcare utilization outcomes. Sensitivity analyses were performed using modeling with a Poisson distribution and as an unadjusted model, with statistical significance set to p < 0.05. RESULTS: Analysis elicited 577 children identified with OSA. Of these, 336 (58.2 %) underwent observation while 241 (41.8 %) underwent AT. The mean age was 6.4 years, with a slight male predominance (60.5 %). Analysis of baseline healthcare utilization patterns revealed that the treatment group had a significantly higher number of baseline inpatient/ED visits and OM visits in comparison to the observation group, but no differences in regards to baseline outpatient visits, or in visits involving URI or AR. Analysis of the entire OSA cohort via D-I-D modelling showed a significantly larger reduction in outpatient visits, secure messages, specialty referrals, and the use of intranasal steroid and LTRA in the treatment group compared to the observation group. Stratification of children based on OSA severity showed that the significant differences in healthcare utilization attributed to surgical treatment were primarily driven by the severe OSA group. Children with severe OSA who underwent AT showed significant reductions in most variables including outpatient visits, inpatient/ED visits, and OM visits. Alternatively, the only significant reductions in healthcare utilization among children with mild OSA treated with AT were in AR visits, intranasal steroid use, and LTRA use. Pattern changes among children with moderate OSA compared similarly to those with mild OSA. CONCLUSION: To the authors' knowledge this study represents the largest available study assessing the impact of AT on healthcare utilization in children with OSA that also considers the effect of OSA severity on utilization patterns. AT appears to decrease healthcare utilization patterns, particularly in children with severe OSA. Alternatively, children with mild or moderate OSA treated with AT had only modest reductions in healthcare utilization patterns.

Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase 3 CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase 3 trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1:1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n= 103 without upfront PTR, n=101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (IQR 59-71). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% CI 16.0-22.2) compared to 20.1 months (95% CI 17.0-25.1) in the upfront PTR arm (p = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (p=0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSION: of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

Thumb Distal Phalanx Giant Enchondroma. A Case Presentation and Literature Review.

Background: Enchordoma of the distal phalange of the thumb is extremely rare. Case presentation: We report a case of 31-year-old man who presented with a pathological fracture of the left thumb. Imaging evaluation revealed a lytic lesion and surgical curettage with bone graft was performed after fracture healing. Histological examination confirmed the diagnosis of enchordoma. The postoperative period was uncomplicated without signs of recurrence. Conclusion:Lytic lesions in the thumb are uncommon occurrences and necessitate a comprehensive examination to determine their potential causes. Given the significant functional role of the thumb compared to other fingers, it is crucial to undergo radiological assessment and further investigation of these lytic lesions.

Synaptic Protein Loss in Extracellular Vesicles Reflects Brain and Retinal Atrophy in People With Multiple Sclerosis.

OBJECTIVES: To assess whether the rate of change in synaptic proteins isolated from neuronally enriched extracellular vesicles (NEVs) is associated with brain and retinal atrophy in people with multiple sclerosis (MS). METHODS: People with MS were followed with serial blood draws, MRI (MRI), and optical coherence tomography (OCT) scans. NEVs were immunocaptured from plasma, and synaptopodin and synaptophysin proteins were measured using ELISA. Subject-specific rates of change in synaptic proteins, as well as brain and retinal atrophy, were determined and correlated. RESULTS: A total of 50 people with MS were included, 46 of whom had MRI and 45 had OCT serially. The rate of change in NEV synaptopodin was associated with whole brain (rho = 0.31; p = 0.04), cortical gray matter (rho = 0.34; p = 0.03), peripapillary retinal nerve fiber layer (rho = 0.37; p = 0.01), and ganglion cell/inner plexiform layer (rho = 0.41; p = 0.006) atrophy. The rate of change in NEV synaptophysin was also correlated with whole brain (rho = 0.31; p = 0.04) and cortical gray matter (rho = 0.31; p = 0.049) atrophy. DISCUSSION: NEV-derived synaptic proteins likely reflect neurodegeneration and may provide additional circulating biomarkers for disease progression in MS.

Validation of the international MOGAD panel proposed criteria: a single-centre US study.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder of the central nervous system. We aimed to evaluate the diagnostic performance of recently proposed MOGAD diagnostic criteria in a real-world patient cohort at a tertiary referral centre. METHODS: We identified all patients who were evaluated at Johns Hopkins and were MOG-IgG seropositive by cell-based assay. We retrospectively applied the proposed MOGAD diagnostic criteria. RESULTS: Among the 122 patients included in this study, 109 fulfilled the diagnostic criteria. Of 64 patients with clear positive MOG-IgG titre, 63 patients also satisfied the supporting clinical or MRI features. Of 58 patients with low positive or unknown MOG-IgG titre, 46 met criteria by fulfilment of the supporting features. The medical records were independently reviewed by two investigators with expertise in demyelinating disease, and patients were assigned empirical clinical diagnoses, with agreement with the application of the MOGAD diagnostic criteria in the majority of cases (90%). CONCLUSIONS: Our findings support the diagnostic utility of the proposed MOGAD diagnostic criteria. Patients with MOGAD met the supporting clinical or MRI features almost universally, which suggests that the criteria can be used to accurately differentiate MOGAD from mimics with low-titre MOG-IgG seropositivity.

Sagittal Balance Parameters and Proximal Junctional Kyphosis in Adolescent Idiopathic Scoliosis.

Background: To review and evaluate multiple preoperative and postoperative sagittal parameters and their association with the risk of developing proximal junctional kyphosis (PJK) in patients with adolescent idiopathic scoliosis (AIS) who undergo correction surgery. Methods: A systematic search was performed in December 2022 in PubMed, Embase and the Cochrane Library to retrieve all the studies relevant to our research. After the study selection and data extraction following PRISMA guidelines, RevMan 5.3 was used for statistical analysis. All the analyzed factors were evaluated by using odds ratios and weighted mean differences with 95% confidence intervals. Moreover, the meta-analysis of proportions via MedCalc was used for analyzing quantitative data from the studies. Results: A total of 22 studies were included in our meta-analysis. All the available values of sagittal parameters were evaluated. Among all the potential risk factors, higher preoperative thoracic kyphosis (Test for overall effect Z = 11.79, p < 0.00001), higher preoperative sagittal vertical axis (SVA) (test for overall effect Z = 11.19, p < 0.00001), greater thoracic kyphosis change post-op. compared to pre-op. (test for overall effect Z = 6.02, p < 0.00001), increased postoperative lumbar lordosis (test for overall effect Z = 3.65, p = 0.0003), higher post-op. SVA (test for overall effect Z = 24.93, p < 0.00001) and a larger pelvic incidence/lumbar lordosis (PI/LL) mismatch (test for overall effect Z = 20.50, p < 0.00001) were found to be the risk factors for PJK after AIS surgery. Moreover, a decreased rod contour angle (RCA) (test for overall effect Z = 3.79, p < 0.0002) and higher proximal junctional angle-rod contour angle (PJA-RCA) (test for overall effect Z = 39.18, p < 0.00001) play a significant role in the risk of developing PJK after AIS correction. Conclusions: Sagittal balance is of great importance when considering the surgical correction of AIS. Many factors in our meta-analysis were found to increase the incidence for PJK such as higher preoperative thoracic kyphosis and pre-op. SVA. Furthermore, increased thoracic kyphosis change, increased post-operative lumbar lordosis, SVA and PI/LL mismatch are also factors that influence the possibility of post-op. PJK. Lastly, RCA and PJA-RCA are two important factors that need attention during AIS, as over-contouring of the rod could lead to PJK in AIS patients.

Occlusal characteristics in modern humans with tooth agenesis.

Non-syndromic permanent tooth agenesis affects a significant proportion of the population, especially if third molars are considered. Although tooth agenesis has been linked to a smaller craniofacial size, reduced facial convexity and a shorter skeletal face, the occlusal characteristics of individuals with tooth agenesis remain largely unexplored. Therefore, this study investigated potential associations between tooth agenesis and metric occlusal traits in 806 individuals (491 with 4.1 missing teeth per subject, including third molars, and 315 without any tooth agenesis). Dentoskeletal morphology was defined through anatomical landmarks on pre-treatment cephalometric radiographs. Multivariate regression models, adjusted for sex and age, showed that tooth agenesis was significantly associated with a reduced overjet, an increased interincisal angle, and shorter upper and lower dental arch lengths, but not with overbite. Moreover, apart from reduced tooth length and dentoalveolar effects, as the number of missing teeth increased the upper front teeth were progressively retruded according to the craniofacial complex and to the face. Thus, tooth agenesis has a substantial influence on dental and occlusal characteristics, as well as on the sagittal position and inclination of anterior teeth. These findings emphasize the necessity for personalized, multidisciplinary approaches in individuals with multiple agenesis to successfully meet treatment goals.

Ancient Loss of Catalytic Selenocysteine Spurred Convergent Adaptation in a Mammalian Oxidoreductase.

Selenocysteine, the 21st amino acid specified by the genetic code, is a rare selenium-containing residue found in the catalytic site of selenoprotein oxidoreductases. Selenocysteine is analogous to the common cysteine amino acid, but its selenium atom offers physical-chemical properties not provided by the corresponding sulfur atom in cysteine. Catalytic sites with selenocysteine in selenoproteins of vertebrates are under strong purifying selection, but one enzyme, glutathione peroxidase 6 (GPX6), independently exchanged selenocysteine for cysteine <100 million years ago in several mammalian lineages. We reconstructed and assayed these ancient enzymes before and after selenocysteine was lost and up to today and found them to have lost their classic ability to reduce hydroperoxides using glutathione. This loss of function, however, was accompanied by additional amino acid changes in the catalytic domain, with protein sites concertedly changing under positive selection across distant lineages abandoning selenocysteine in glutathione peroxidase 6. This demonstrates a narrow evolutionary range in maintaining fitness when sulfur in cysteine impairs the catalytic activity of this protein, with pleiotropy and epistasis likely driving the observed convergent evolution. We propose that the mutations shared across distinct lineages may trigger enzymatic properties beyond those in classic glutathione peroxidases, rather than simply recovering catalytic rate. These findings are an unusual example of adaptive convergence across mammalian selenoproteins, with the evolutionary signatures possibly representing the evolution of novel oxidoreductase functions.

Acute Optic Neuropathy in Older Adults: Differentiating Between MOGAD Optic Neuritis and Nonarteritic Anterior Ischemic Optic Neuropathy.

BACKGROUND AND OBJECTIVES: Myelin oligodendrocyte glycoprotein antibody-associated disease optic neuritis (MOGAD-ON) and nonarteritic anterior ischemic optic neuropathy (NAION) can cause acute optic neuropathy in older adults but have different managements. We aimed to determine differentiating factors between MOGAD-ON and NAION and the frequency of serum MOG-IgG false positivity among patients with NAION. METHODS: In this international, multicenter, case-control study at tertiary neuro-ophthalmology centers, patients with MOGAD presenting with unilateral optic neuritis as their first attack at age 45 years or older and age-matched and sex-matched patients with NAION were included. Comorbidities, clinical presentations, acute optic disc findings, optical coherence tomography (OCT) findings, and outcomes were compared between MOGAD-ON and NAION. Multivariate analysis was performed to find statistically significant predictors of MOGAD-ON. A separate review of consecutive NAION patients seen at Mayo Clinic, Rochester, from 2018 to 2022, was conducted to estimate the frequency of false-positive MOG-IgG in this population. RESULTS: Sixty-four patients with unilateral MOGAD-ON were compared with 64 patients with NAION. Among patients with MOGAD-ON, the median age at onset was 56 (interquartile range [IQR] 50-61) years, 70% were female, and 78% were White. Multivariate analysis showed that eye pain was strongly associated with MOGAD-ON (OR 32.905; 95% CI 2.299-473.181), while crowded optic disc (OR 0.033; 95% CI 0.002-0.492) and altitudinal visual field defect (OR 0.028; 95% CI 0.002-0.521) were strongly associated with NAION. On OCT, peripapillary retinal nerve fiber layer (pRNFL) thickness in unilateral MOGAD-ON was lower than in NAION (median 114 vs 201 µm, p < 0.001; median pRNFL thickening 25 vs 102 µm, p < 0.001). MOGAD-ON had more severe vision loss at nadir (median logMAR 1.0 vs 0.3, p < 0.001), but better recovery (median logMAR 0.1 vs 0.3, p = 0.002). In the cohort of consecutive NAION patients, 66/212 (31%) patients with NAION were tested for MOG-IgG and 8% (95% CI 1%-14%) of those had false-positive serum MOG-IgG at low titers. DISCUSSION: Acute unilateral optic neuropathy with optic disc edema in older adults can be caused by either MOGAD-ON or NAION. Detailed history, the degree of pRNFL swelling on OCT, and visual outcomes can help differentiate the entities and prevent indiscriminate serum MOG-IgG testing in all patients with acute optic neuropathy.

Piperazine-Fused Cyclic Disulfides Unlock High-Performance Bioreductive Probes of Thioredoxins and Bifunctional Reagents for Thiol Redox Biology.

We report piperazine-fused six-membered-cyclic disulfides as redox substrates that unlock best-in-class bioreduction probes for live cell biology, since their self-immolation after reduction is unprecedentedly rapid. We develop scalable, diastereomerically pure, six-step syntheses that access four key cis- and trans-piperazine-fused cyclic dichalcogenides without chromatography. Fluorogenic redox probes using the disulfide piperazines are activated >100-fold faster than the prior art monoamines, allowing us to deconvolute reduction and cyclization rates during activation. The cis- and trans-fused diastereomers have remarkably different reductant specificities, which we trace back to piperazine boat/chair conformation effects: the cis-fused disulfide C-DiThia is activated only by strong vicinal dithiol reductants, but the trans-disulfide T-DiThia is activated even by moderate concentrations of monothiols such as GSH. Thus, in cellular applications, cis-disulfide probes selectively report on the reductive activity of the powerful thioredoxin proteins, while trans-disulfides are rapidly but promiscuously reactive. Finally, we showcase late-stage diversifications of the piperazine-disulfides, promising their broad applicability as redox-cleavable cores for probes and prodrugs that interface powerfully with cellular thiol/disulfide redox biology, for solid phase synthesis and purification, and for stimulus-responsive linkers in bifunctional reagents and antibody-drug conjugates - in addition to their dithiols' potential as high-performance reducing agents.

Predicting response to neoadjuvant chemotherapy with liquid biopsies and multiparametric MRI in patients with breast cancer.

Accurate prediction of response to neoadjuvant chemotherapy (NAC) can help tailor treatment to individual patients' needs. Little is known about the combination of liquid biopsies and computer extracted features from multiparametric magnetic resonance imaging (MRI) for the prediction of NAC response in breast cancer. Here, we report on a prospective study with the aim to explore the predictive potential of this combination in adjunct to standard clinical and pathological information before, during and after NAC. The study was performed in four Dutch hospitals. Patients without metastases treated with NAC underwent 3 T multiparametric MRI scans before, during and after NAC. Liquid biopsies were obtained before every chemotherapy cycle and before surgery. Prediction models were developed using penalized linear regression to forecast residual cancer burden after NAC and evaluated for pathologic complete response (pCR) using leave-one-out-cross-validation (LOOCV). Sixty-one patients were included. Twenty-three patients (38%) achieved pCR. Most prediction models yielded the highest estimated LOOCV area under the curve (AUC) at the post-treatment timepoint. A clinical-only model including tumor grade, nodal status and receptor subtype yielded an estimated LOOCV AUC for pCR of 0.76, which increased to 0.82 by incorporating post-treatment radiological MRI assessment (i.e., the "clinical-radiological" model). The estimated LOOCV AUC was 0.84 after incorporation of computer-extracted MRI features, and 0.85 when liquid biopsy information was added instead of the radiological MRI assessment. Adding liquid biopsy information to the clinical-radiological resulted in an estimated LOOCV AUC of 0.86. In conclusion, inclusion of liquid biopsy-derived markers in clinical-radiological prediction models may have potential to improve prediction of pCR after NAC in breast cancer.

Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.

Background: Bile acid metabolism is altered in multiple sclerosis (MS) and tauroursodeoxycholic acid (TUDCA) supplementation ameliorated disease in mouse models of MS. Methods: Global metabolomics was performed in an observational cohort of people with MS followed by pathway analysis to examine relationships between baseline metabolite levels and subsequent brain and retinal atrophy. A double-blind, placebo-controlled trial, was completed in people with progressive MS (PMS), randomized to receive either TUDCA (2g daily) or placebo for 16 weeks. Participants were followed with serial clinical and laboratory assessments. Primary outcomes were safety and tolerability of TUDCA, and exploratory outcomes included changes in clinical, laboratory and gut microbiome parameters. Results: In the observational cohort, higher primary bile acid levels at baseline predicted slower whole brain, brain substructure and specific retinal layer atrophy. In the clinical trial, 47 participants were included in our analyses (21 in placebo arm, 26 in TUDCA arm). Adverse events did not significantly differ between arms (p=0.77). The TUDCA arm demonstrated increased serum levels of multiple bile acids. No significant differences were noted in clinical or fluid biomarker outcomes. Central memory CD4+ and Th1/17 cells decreased, while CD4+ naïve cells increased in the TUDCA arm compared to placebo. Changes in the composition and function of gut microbiota were also noted in the TUDCA arm compared to placebo. Conclusion: Bile acid metabolism in MS is linked with brain and retinal atrophy. TUDCA supplementation in PMS is safe, tolerable and has measurable biological effects that warrant further evaluation in larger trials with a longer treatment duration.

Rituximab for Multiple Sclerosis: Hiding in Plain Sight

In February 2023, following extensive discussions with stakeholders and data review, the Institute for Clinical and Economic Review issued final policy recommendations for treatment of relapsing multiple sclerosis (RMS)1: "All stakeholders have a responsibility and an important role to play in ensuring that all effective treatment options for patients with RMS, including off-label use of rituximab, are utilized in ways to help improve affordability and access and reduce health inequities." The report calls on payers to remove barriers to rituximab coverage, the American Academy of Neurology and the National MS Society to publicly endorse rituximab for RMS, and clinicians to advocate for coverage of rituximab and its biosimilars. In July 2023, the World Health Organization listed rituximab as an essential medicine for MS.2 Yet not much has changed. Food and Drug Administration (FDA)-approved MS disease-modifying therapies continue to generate enormous profits for pharma, and rituximab remains hidden in plain sight.

A Noncanonical CD56dimCD16dim/- NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases.

Neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein Ab disease, and autoimmune myasthenia gravis (MG) are autoantibody-mediated neurologic conditions where autoantibodies can induce Ab-dependent cellular cytotoxicity (ADCC), a NK cell-mediated effector function. However, whether ADCC is a pathogenic mechanism in patients with these conditions has not been confirmed. We sought to characterize circulatory NK cells using functional assays, phenotyping, and transcriptomics to elucidate their role in pathology. NK cells from NMOSD patients and MG patients with elevated disease burden exhibited reduced ADCC and CD56dimCD16hi NK cells, along with an elevated frequency of CD56dimCD16dim/- NK cells. We determined that ADCC induces a similar phenotypic shift in vitro. Bulk RNA sequencing distinguished the CD56dimCD16dim/- population from the canonical CD56dimCD16hi cytotoxic and CD56hiCD16- immunomodulatory subsets, as well as CD56hiCD16+ NK cells. Multiparameter immunophenotyping of NK cell markers, functional proteins, and receptors similarly showed that the CD56dimCD16dim/- subset exhibits a unique profile while still maintaining expression of characteristic NK markers CD56, CD94, and NKp44. Notably, expression of perforin and granzyme is reduced in comparison with CD56dimCD16hi NK cells. Moreover, they exhibit elevated trogocytosis capability, HLA-DR expression, and many chemokine receptors, including CCR7. In contrast with NMOSD and MG, myelin oligodendrocyte glycoprotein Ab disease NK cells did not exhibit functional, phenotypic, or transcriptomic perturbations. In summary, CD56dimCD16dim/- NK cells are a distinct peripheral blood immune cell population in humans elevated upon prior cytotoxic activity by the CD56dimCD16hi NK cell subset. The elevation of this subset in NMOSD and MG patients suggests prior ADCC activity.

Epidemiology of and Risk Factors in Postoperative Complications from Robotically Assisted Laparoscopic Radical Prostatectomy in Contemporary National Surgical Quality Improvement Program Data.

Introduction: For localized clinically significant prostate cancer (csPCa), robotically assisted laparoscopic radical prostatectomy (RALP) is the gold standard surgical treatment. Despite low overall complication rate, continued quality assurance (QA) efforts to minimize complications of RALP are important, particularly given movement toward same-day discharge. In 2019, National Surgical Quality Improvement Program (NSQIP) began collecting RALP-specific data. In this study, we assessed pre- and perioperative factors associated with postoperative complications for RALP to further QA efforts. Materials and Methods: Surgical records of csPCa patients who underwent RALP were retrieved from the 2019 to 2021 NSQIP database, including new RALP-specific data. Multivariate logistic regression evaluated the association between risk factors and outcomes specific to RALP and pelvic lymph node dissection (PLND). Input variables included American Society of Anesthesiologists (ASA) class, age, operative time, and body mass index (BMI). Variables from the extended dataset with PLND information included number of nodes evaluated, perioperative antibiotics, postoperative venous thromboembolism (VTE) prophylaxis, history of prior pelvic surgery, and history of prior radiotherapy (RT). Outcomes of interest were any surgical complication, infection, pulmonary embolism, deep venous thrombosis, acute kidney injury, pneumonia, lymphocele, and urinary/anastomotic leak (UAL). Results: A total of 11,811 patients were included with 6.1% experiencing any complication. Prior RT, prior pelvic surgery, older age, higher BMI, lack of perioperative antibiotic therapy, longer operative time, PLND, and number of lymph nodes dissected were associated with higher risk of postoperative complications. Regarding procedure-specific complications, there were increased odds of UAL with prior RT, prior pelvic surgery, longer operative time, and higher BMI. Odds of developing lymphocele increased with prior pelvic surgery, performance of PLND, and increased number of nodes evaluated. Conclusion: In contemporary NSQIP data, RALP is associated with low complication rates; however, these rates have increased compared with historical studies. Attention to and counseling regarding risk factors for peri- and postoperative complications are important to set expectations and minimize risk of unplanned return to a health care setting after discharge.

Orofacial Myofunctional Therapy for Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

OBJECTIVE: Orofacial myofunctional therapy (OMT) is an alternative form of treatment of obstructive sleep apnea (OSA), that incorporates various exercises to optimize tongue placement and increase oropharyngeal tone. The objective of this systematic review and meta-analysis is to determine the efficacy of OMT in OSA patients. DATA SOURCES: PubMed/Medline, EMBASE, Cochrane, Web of Science. REVIEW METHODS: Using PRISMA guidelines, a directed search strategy was performed for randomized control trials (RCTs) published prior to March 24, 2023, featuring 10+ patients with OSA undergoing mono-therapeutic OMT. The primary outcome of interest was apnea-hypopnea index (AHI). Secondary outcomes included subjective sleepiness, sleep-related quality-of-life, and snoring frequency. RESULTS: Of the 1244 abstracts that were identified, 7 RCTs involving 310 patients met inclusion criteria. Adult OMT patients had a statistically significant improvement in AHI (MD -10.2; 95% CI, -15.6, -4.8, p < 0.05), subjective sleepiness (Epworth Sleepiness Scale; MD -5.66; 95% CI, -6.82, -4.5, p < 0.05), sleep-related quality-of-life (Pittsburgh Sleep Quality Index; MD -3.00; 95% CI, -4.52, -1.49, p < 0.05), and minimum oxygen saturation (MD 2.71; 95% CI, 0.23, 5.18, p < 0.05) when compared with sham OMT or no therapy. Within the single RCT featuring pediatric OMT patients, patients had poor compliance (<50%) and did not show any improvements in AHI, minimum oxygen saturation, or snoring frequency. CONCLUSION: OMT may provide a reasonable alternative for OSA patients who cannot tolerate CPAP or other more established treatment options. OMT benefits appear limited in children due to poor compliance. More studies are required to evaluate compliance and the long-term effects of OMT on OSA outcomes. LEVEL OF EVIDENCE: 1 Laryngoscope, 134:480-495, 2024.

A multicenter pilot study evaluating simplified central vein assessment for the diagnosis of multiple sclerosis.

BACKGROUND: The central vein sign (CVS) is a proposed magnetic resonance imaging (MRI) biomarker for multiple sclerosis (MS); the optimal method for abbreviated CVS scoring is not yet established. OBJECTIVE: The aim of this study was to evaluate the performance of a simplified approach to CVS assessment in a multicenter study of patients being evaluated for suspected MS. METHODS: Adults referred for possible MS to 10 sites were recruited. A post-Gd 3D T2*-weighted MRI sequence (FLAIR*) was obtained in each subject. Trained raters at each site identified up to six CVS-positive lesions per FLAIR* scan. Diagnostic performance of CVS was evaluated for a diagnosis of MS which had been confirmed using the 2017 McDonald criteria at thresholds including three positive lesions (Select-3*) and six positive lesions (Select-6*). Inter-rater reliability assessments were performed. RESULTS: Overall, 78 participants were analyzed; 37 (47%) were diagnosed with MS, and 41 (53%) were not. The mean age of participants was 45 (range: 19-64) years, and most were female (n = 55, 71%). The area under the receiver operating characteristic curve (AUROC) for the simplified counting method was 0.83 (95% CI: 0.73-0.93). Select-3* and Select-6* had sensitivity of 81% and 65% and specificity of 68% and 98%, respectively. Inter-rater agreement was 78% for Select-3* and 83% for Select-6*. CONCLUSION: A simplified method for CVS assessment in patients referred for suspected MS demonstrated good diagnostic performance and inter-rater agreement.

Third molar agenesis relates to human craniofacial form.

OBJECTIVE: To investigate the association between the number of third molars and craniofacial shape. SUBJECTS AND METHODS: The study sample comprised 470 individuals (194 males and 276 females), out of whom 310 (124 males, mean age: 14.6 years and 186 females, mean age: 14.1 years) had a full permanent dentition including third molars and 160 (70 males, mean age: 13.7 years and 90 females, mean age: 13.9 years) had at least one missing third molar. Pre-orthodontic treatment cephalometric images were digitized using 127 landmarks to describe the shape of the entire craniofacial configuration, the cranial base, the maxilla, and the mandible. The shapes of the various configurations were described by principal components (PCs) of shape. The effect of third molar agenesis on craniofacial shape was evaluated with multivariate regression models, considering shape PCs as the dependent variables, and age and sex as predictors. RESULTS: There was a strong association between third molar agenesis and the shape of all craniofacial configurations in both sexes. Individuals with missing third molars presented a less convex craniofacial configuration, a shorter anterior facial height and a more retrusive maxilla and mandible. In cases with third molar agenesis only in one jaw, shape differences were also evident in the opposing jaw. LIMITATIONS: Interpretation of study outcomes should take into consideration the two-dimensional data and the analysis of only white-European subjects. CONCLUSIONS: There is a strong association between third molar formation and craniofacial shape. The effect is rather generalized than local and is potentially linked to an ongoing evolutionary mechanism that leads to smaller and fewer teeth, as well as smaller craniofacial configurations, in modern humans.