Nanoconfinement Enables Photoelectrochemical Selective Oxidation of Glycerol via the Microscale Fluid Effect.

The glycerol oxidation reaction (GOR) run with photoelectrochemical cells (PECs) is one of the most promising ways to upgrade biomass because it is thermodynamically favorable, while irreversible overoxidation leads to unsatisfactory product selectivities. Herein, a tunable one-dimensional nanoconfined environment was introduced into the GOR process, which accelerated mass transfer of glycerol via the microscale fluid effect and changed the main oxidation product from formic acid (FA) to glyceraldehyde (GLD), which led to retention of the heavier multicarbon products. The rate of glycerol diffusion in the nanochannels increased by a factor of 4.92 with decreasing inner diameters. The main product from the PEC-selective oxidation of glycerol changed from the C1 product FA to the C3 product GLD with a great selectivity of 60.7%. This work provides a favorable approach for inhibiting further oxidation of multicarbon products and illustrates the importance of microenvironmental regulation in biomass oxidation.

Management of undifferentiated embryonal sarcoma of the liver: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim of this study was to define current management strategies and outcomes for these patients using a multi-institutional dataset curated by the Pediatric Surgical Oncology Research Collaborative. METHODS: Data were collected retrospectively for patients with UESL treated across 17 children's hospitals in North America from 1989 to 2019. Factors analyzed included patient and tumor characteristics, PRETEXT group, operative details, and neoadjuvant/adjuvant regimens. Event-free and overall survival (EFS, OS) were the primary and secondary outcomes, respectively. RESULTS: Seventy-eight patients were identified with a median age of 9.9 years [interquartile range [IQR): 7-12]. Twenty-seven patients underwent resection at diagnosis, and 47 patients underwent delayed resection, including eight liver transplants. Neoadjuvant chemotherapy led to a median change in maximum tumor diameter of 1.6 cm [IQR: 0.0-4.4] and greater than 90% tumor necrosis in 79% of the patients undergoing delayed resection. R0 resections were accomplished in 63 patients (81%). Univariate analysis found that metastatic disease impacted OS, and completeness of resection impacted both EFS and OS, while multivariate analysis revealed that R0 resection was associated with decreased expected hazards of experiencing an event [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.04-0.6]. At a median follow-up of 4 years [IQR: 2-8], the EFS was 70.0% [95% CI: 60%-82%] and OS was 83% [95% CI: 75%-93%]. CONCLUSION: Complete resection is associated with improved survival for patients with UESL. Neoadjuvant chemotherapy causes minimal radiographic response, but significant tumor necrosis.

Multisite prospective study of perioperative pain management practices for anterior cruciate ligament reconstruction in adolescents: Society for Pediatric Anesthesia Improvement Network (SPAIN) Project Report.

INTRODUCTION: Although 200 000 adolescents undergo anterior cruciate ligament reconstruction (ACLR) surgery annually, no benchmarks for pediatric post-ACLR pain management exist. We created a multicenter, prospective, observational registry to describe pain practices, pain, and functional recovery after pediatric ACLR. METHODS: Participants (n=519; 12-17.5 years) were enrolled from 15 sites over 2 years. Data on perioperative management and surgical factors were collected. Pain/opioid use and Lysholm scores were assessed preoperatively, on postoperative day 1 (POD1), POD3, week 6, and month 6. Descriptive statistics and trends for opioid use, pain, and function are presented. RESULTS: Regional analgesia was performed in 447/519 (86%) subjects; of these, adductor canal single shot was most frequent (54%), nerve catheters placed in 24%, and perineural adjuvants used in 43%. On POD1, POD3, week 6, and month 6, survey response rates were 73%, 71%, 61%, and 45%, respectively. Over these respective time points, pain score >3/10 was reported by 64% (95% CI: 59% to 69%), 46% (95% CI: 41% to 52%), 5% (95% CI: 3% to 8%), and 3% (95% CI: 1% to 6%); the number of daily oxycodone doses used was 2.8 (SD 0.19), 1.8 (SD 0.13), 0, and 0. There was considerable variability in timing and tests for postdischarge functional assessments. Numbness and weakness were reported by 11% and 4% at week 6 (n=315) and 16% and 2% at month 6 (n=233), respectively. CONCLUSION: We found substantial variability in the use of blocks to manage post-ACLR pain in children, with a small percentage experiencing long-term pain and neurological symptoms. Studies are needed to determine best practices for regional anesthesia and functional assessments in this patient population.

Differential RNA Expression Between Metastatic and Primary Neuroblastoma Cells.

INTRODUCTION: Neuroblastoma (NB) is the most common extra-cranial malignancy in children. Poor survival in high-risk NB is attributed to recurrent metastatic disease. To better study metastatic disease, we used a novel mouse model to investigate differential gene expression between primary tumor cells and metastatic cells. We hypothesized that metastatic NB cells have a different gene expression profile from primary tumor cells and cultured cells. METHODS: Using three human NB cell lines (NGP, CHLA255, and SH-SY5Y), orthotopic xenografts were established in immunodeficient nod/scid gamma mice via subcapsular renal injection. Mice were sacrificed and NB cells were isolated from the primary tumor and from sites of metastasis (bone marrow, liver). RNA sequencing, gene set analysis, and pathway analysis were performed to identify differentially expressed genes and molecular pathways in the metastatic cells compared to primary tumor cells. RESULTS: There were 266 differentially expressed genes in metastatic tumor cells (bone marrow and liver combined) compared to primary tumor cells. The top upregulated gene was KCNK1 and the top downregulated genes were PDE7B and NEBL. Top upregulated pathways in the metastatic cells were involved in ion transport, cell signaling, and cell proliferation. Top downregulated pathways were involved in DNA synthesis, transcription, and cellular metabolism. CONCLUSIONS: In metastatic NB cells, our study identified the upregulation of biologic processes involved in cell cycle regulation, cell proliferation, migration, and invasion. Ongoing studies aim to validate downstream translation of these genomic alterations, as well as target these pathways to more effectively suppress and inhibit recurrent metastatic disease in NB.

A Nanopore Sequencing-based Pharmacogenomic Panel to Personalize Tuberculosis Drug Dosing.

RATIONALE: Standardized dosing of anti-tubercular (TB) drugs leads to variable plasma drug levels, which are associated with adverse drug reactions, delayed treatment response, and relapse. Mutations in genes affecting drug metabolism explain considerable interindividual pharmacokinetic variability; however, pharmacogenomic (PGx) assays that predict metabolism of anti-TB drugs have been lacking. OBJECTIVES: To develop a Nanopore sequencing panel and validate its performance in active TB patients to personalize treatment dosing. MEASUREMENTS AND MAIN RESULTS: We developed a Nanopore sequencing panel targeting 15 single nucleotide polymorphisms (SNP) in 5 genes affecting the metabolism of anti-tuberculous drugs. For validation, we sequenced DNA samples (n=48) from the 1000 genomes project and compared variant calling accuracy with Illumina genome sequencing. We then sequenced DNA samples from patients with active TB (n=100) from South Africa on a MinION Mk1C and evaluated the relationship between genotypes and pharmacokinetic parameters for INH and RIF. RESULTS: The PGx panel achieved 100% concordance with Illumina sequencing in variant identification for the samples from the 1000 Genomes Project. In the clinical cohort, coverage was >100x for 1498/1500 (99.8%) amplicons across the 100 samples. One third (33%) of participants were identified as slow, 47% were intermediate and 20% were rapid isoniazid acetylators. Isoniazid clearance was 2.2 times higher among intermediate acetylators and 3.8 times higher among rapid acetylators compared with slow acetylators (p<0.0001).. Rifampin clearance was 17.3% (2.50-29.9) lower in individuals with homozygous AADAC rs1803155 G>A substitutions (p=0.0015). CONCLUSION: Targeted sequencing can enable detection of polymorphisms influencing TB drug metabolism on a low-cost, portable instrument to personalize dosing for TB treatment or prevention. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Evaluation of Postoperative Outcomes After Enterostomy Closure in Low Body Weight Infants: A Multi-Center Retrospective Analysis.

BACKGROUND: The minimum weight for enterostomy closure (EC) in infants remains debated with the current acceptable cut-off of >2 kg. As enterostomy-related complications or high enterostomy output (>30cc/kg/d) may prohibit a premature infant from reaching 2 kg, additional data is needed to evaluate the safety of EC in infants <2 kg. The objective of this study was to evaluate postoperative outcomes in low body weight (<2 kg) infants undergoing EC compared to larger infants. METHODS: We performed a multi-center retrospective analysis from 1/1/2012-12/31/2022 of all infants (age <1 year) who were <4 kg at time of EC. Primary outcomes included postoperative complications and 30-day mortality. Non-parametric analysis was performed using the Kruskal-Wallis one-way analysis of variance and chi-square tests. Univariable logistic regression was performed to identify factors associated with postoperative complications. RESULTS: Of 92 infants, 15 infants (16.3%) underwent EC at <2 kg, 16 (17.4%) at 2-2.49 kg, 31 (33.7%) at 2.5-2.99 kg, and 30 (32.6%) at ≥3 kg. Infants <2 kg at time of EC exhibited higher rates of hyperbilirubinemia (P = .030), neurologic comorbidities (P = .030), and high enterostomy output (P = .041). There was no difference in postoperative complications (P = .460) or 30-day mortality (P = .460) between the <2 kg group and larger weight groups. Low body weight was not associated with an increased risk for developing a postoperative complication (OR: 1.001, 95% CI: 1.001-1.001; P = .032). CONCLUSION: Our findings suggest that EC in infants <2 kg may be safe with comparable postoperative outcomes to larger weight infants. Thus, the timing of EC should be based on the infant's physiologic status, in contrast to a predetermined minimum weight cut-off.

A Multi-Institutional Study Comparing Stoma Location in Neonates With Intestinal Perforation.

INTRODUCTION: Neonates with intestinal perforation often require laparotomy and intestinal stoma creation, with the stoma placed in either the laparotomy incision or a separate site. We aimed to investigate if stoma location is associated with risk of postoperative wound complications. METHODS: A multi-institutional retrospective review was performed for neonates ≤3 mo who underwent emergent laparotomy and intestinal stoma creation for intestinal perforation between January 1, 2009 and April 1, 2021. Patients were stratified by stoma location (laparotomy incision versus separate site). Outcomes included wound infection/dehiscence, stoma irritation, retraction, stricture, and prolapse. Multivariable regression identified factors associated with postoperative wound complications, controlling for gestational age, age and weight at surgery, and diagnosis. RESULTS: Overall, 79 neonates of median gestational age 28.8 wk (interquartile range [IQR]: 26.0-34.2 wk), median age 5 d (IQR: 2-11 d) and median weight 1.4 kg (IQR: 0.9-2.42 kg) had perforated bowel from necrotizing enterocolitis (40.5%), focal intestinal perforation (31.6%), or other etiologies (27.8%). Stomas were placed in the laparotomy incision for 41 (51.9%) patients and separate sites in 38 (48.1%) patients. Wound infection/dehiscence occurred in 7 (17.1%) neonates with laparotomy stomas and 5 (13.2%) neonates with separate site stomas (P = 0.63). There were no significant differences in peristomal irritation, stoma retraction, or stoma stricture between the two groups. On multivariable regression, separate site stomas were associated with increased likelihood of prolapse (odds ratio 6.54; 95% confidence interval: 1.14-37.5). CONCLUSIONS: Stoma incorporation within the laparotomy incision is not associated with wound complications. Separate site stomas may be associated with prolapse. Patient factors should be considered when planning stoma location in neonates undergoing surgery for intestinal perforation.

Dietary Intake of Antioxidant Vitamins and Its Relation to the Progression of Chronic Kidney Disease in Adults With Preserved Renal Function.

OBJECTIVE: It is expected that antioxidants contribute to slow the progression of chronic kidney disease (CKD). However, there are no data on the protective effect of dietary antioxidant vitamins on CKD. The purpose of study was to evaluate the renoprotective effect of dietary antioxidant vitamins in the general population. DESIGN AND METHODS: The study participants were 127,081 Korean adults with preserved renal function with estimated glomerular filtration rate ≥60 mL/min/1.73 m2. They were categorized into 3 groups by tertile levels of dietary antioxidant vitamins intake including vitamins C, E, and A. Cox proportional hazard assumption was used to calculate multivariable hazard ratios and 95% confidence interval for the incident moderate to severe CKD (adjusted hazard ratio [95% confidence interval]) according to tertile levels of dietary intake of antioxidant vitamins. Subgroup analysis was conducted to evaluate the risk of progression from normal to mildly decreased renal function, and from mildly decreased renal function to moderate to severe CKD. RESULTS: The risk of moderate to severe CKD was not significantly associated with the third tertile of dietary antioxidant vitamin intake including vitamin C (1.02 [0.78-1.34]), E (0.96 [0.73-1.27]), and A (0.98 [0.74-1.29]). Additionally, any tertile groups didn't show the significant association with the risk of moderate to severe CKD. Subgroup analysis also didn't show the decreased risk of progression from normal to mildly decreased renal function, and from mildly decreased renal function to moderate to severe CKD in any tertile groups. CONCLUSION: Dietary intake of vitamins C, E, and A was not significantly associated with the risk of CKD progression.

Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma.

BACKGROUND: Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3's role in promoting USC pathology is lacking. METHODS: We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3's impact on cell function. RESULTS: TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids. CONCLUSION: These findings suggest inhibiting Gal3 may benefit USC patients.

Precision Oncology in Pediatric Cancer Surgery.

Pediatric precision oncology has provided a greater understanding of the wide range of molecular alterations in difficult-to-treat or rare tumors with the aims of increasing survival as well as decreasing toxicity and morbidity from current cytotoxic therapies. In this article, the authors discuss the current state of pediatric precision oncology which has increased access to novel targeted therapies while also providing a framework for clinical implementation in this unique population. The authors evaluate the targetable mutations currently under investigation-with a focus on pediatric solid tumors-and discuss the key surgical implications associated with novel targeted therapies.

The First Generation of Asian American Pediatric Surgical Trainees in North America.

INTRODUCTION: Pediatric surgical trainees come from diverse races and ethnicities. However, Asian-Americans (AAs) including West, South, and East Asians may represent a unique group of individuals. We sought to identify any unique challenges and experiences. METHODS: Pediatric surgical trainees were identified from, "The Genealogy of North American Pediatric Surgery: From Ladd to Now" and "Celebrating 50 Years: Canadian Association of Paediatric Surgeons/Association Canadienne de Chirurgie Pediatrique". A database was compiled, and AAs identified who completed their pediatric surgical training on or before 1980. Personal interviews and online sources provided further information. RESULTS: Of 635 pediatric surgical trainees in North America (NA) there were 49 AA trainees (7.7%). There was insufficient information for seven, thus leaving 42 (41 male, one female) for review. The region of Asia of origin included 16 East, 16 West, and 10 South. Thirty-seven (88.0%) had moved to NA for training. The most frequent training programs included seven from Toronto and four each at Buffalo, Detroit, Pittsburgh, and Chicago (Children's Memorial). Thirty-five (83%) trainees spent most of their careers in NA while 7 (17%) practiced in their home country. CONCLUSIONS: The first AA pediatric surgical trainees voiced few examples of discrimination but indicated needs to adjust to the NA culture and often confusion over non-Western names. Mentorship was valued and gratitude expressed over the opportunity offered to train in NA. While some had intended to return to their home countries, plans changed due to meeting spouses or political turmoil. Many of those reviewed sought each other out at national meetings.

Communication Delay Outlier Detection and Compensation for Teleoperation Using Stochastic State Estimation.

There have been numerous studies attempting to overcome the limitations of current autonomous driving technologies. However, there is no doubt that it is challenging to promise integrity of safety regarding urban driving scenarios and dynamic driving environments. Among the reported countermeasures to supplement the uncertain behavior of autonomous vehicles, teleoperation of the vehicle has been introduced to deal with the disengagement of autonomous driving. However, teleoperation can lead the vehicle to unforeseen and hazardous situations from the viewpoint of wireless communication stability. In particular, communication delay outliers that severely deviate from the passive communication delay should be highlighted because they could hamper the cognition of the circumstances monitored by the teleoperator, or the control signal could be contaminated regardless of the teleoperator's intention. In this study, communication delay outliers were detected and classified based on the stochastic approach (passive delays and outliers were estimated as 98.67% and 1.33%, respectively). Results indicate that communication delay outliers can be automatically detected, independently of the real-time quality of wireless communication stability. Moreover, the proposed framework demonstrates resilience against outliers, thereby mitigating potential performance degradation.

Loop extrusion-mediated plasmid DNA cleavage by the bacterial SMC Wadjet complex.

Structural maintenance of chromosomes (SMC) protein complexes play pivotal roles in genome organization and maintenance across all domains of life. In prokaryotes, SMC family Wadjet complexes structurally resemble the widespread MukBEF genome-organizing complexes but serve a defensive role by inhibiting plasmid transformation. We previously showed that Wadjet specifically cleaves circular DNA; however, the molecular mechanism underlying DNA substrate recognition remains unclear. Here, we use in vitro single-molecule imaging to directly visualize DNA loop extrusion and plasmid cleavage by Wadjet. We find that Wadjet is a symmetric DNA loop extruder that simultaneously reels in DNA from both sides of a growing loop and that this activity requires a dimeric JetABC supercomplex containing two dimers of the JetC motor subunit. On surface-anchored plasmid DNAs, Wadjet extrudes the full length of a 44 kilobase pair plasmid, stalls, and then cleaves DNA. Our findings reveal the role of loop extrusion in the specific recognition and elimination of plasmids by Wadjet, and establish loop extrusion as an evolutionarily conserved mechanism among SMC complexes across kingdoms of life.

Adolescent and Parent Perceptions of Postoperative Opioid Use: A Qualitative, Thematic Analysis.

BACKGROUND: Little is known about how families make decisions regarding postoperative prescription opioid consumption. This qualitative study examines adolescent and parent perspectives on postoperative prescription opioid use. METHODS: We recruited adolescents aged 13-20 years old who received a postoperative opioid prescription and their parents from a previous longitudinal cohort study. We employed purposive sampling for recruitment to reflect local community sociodemographics including race/ethnicity, health literacy, and Spanish-language preference then conducted thematic analysis of focus group feedback. RESULTS: Participants met in four virtual focus groups: adolescents from English-speaking households(n = 2), adolescents from Spanish-speaking households(n = 5), English-speaking parents(n = 4), and Spanish-speaking parents (n = 4). Five themes emerged: Parents (1) feared opioid use would result in overdose or addiction and (2) desired information about alternative medical and behavioral strategies to minimize use. (3) Parents felt empowered to manage their adolescent's opioid use and trusted their adolescent to prompt them for opioids. Adolescents trusted their parents to manage their opioid use but maintained their autonomy to limit opioid consumption when experiencing undesirable side effects. (4) Some adolescents and parents endorsed a preference for "not taking medication" in their households. (5) Both parents and adolescents reported previous knowledge of opioids prior to surgery, with adolescents learning more nuanced information about opioid safety after their surgeries. CONCLUSIONS: Families feel empowered to manage their postoperative prescription opioid use but fear the negative effects of opioids and desire information on alternatives. Evidence-based, family-centric education from providers in a language preferred by the family could mitigate families' concerns and contribute to improved pain control and safety. LEVEL OF EVIDENCE: IV.

Optimizing the Postoperative Management of Children Undergoing Resection of High-Risk Abdominal Neuroblastoma.

BACKGROUND: Surgical resection is a mainstay of treatment in high-risk neuroblastoma (HR-NB), but there exists wide variability in perioperative management practices. The aim of this study was to evaluate two standardized adult perioperative enhanced recovery practices (ERPs) in pediatric patients undergoing open resection of abdominal HR-NB. METHODS: All patients with abdominal HR-NB surgically resected at a free-standing children's hospital between 12/2010 and 7/2020 were retrospectively reviewed. Perioperative ERPs of interest included avoidance of routine nasogastric tube (NGT) use and the use of neuraxial anesthesia. Primary outcomes included time to enteral intake, urinary catheter use, opioid utilization, and length of stay (LOS). RESULTS: Overall, 37 children, median age 33 months (IQR: 20-48 months), were identified. Avoidance of an NGT allowed for earlier feeding after surgery (P = .03). Neuraxial anesthesia use more frequently required an indwelling urinary catheter (P < .01) for a longer duration (P = .02), with no difference in total opioid utilization (P = .77) compared to patients without neuraxial anesthesia. Postoperative LOS was unaffected by avoidance of routine NGT use (P = .68) or use of neuraxial anesthesia (P = .89). CONCLUSION: Children undergoing open resection of abdominal HR-NB initiated diet sooner when an NGT was not left postoperatively, and the need for a urinary catheter was significantly higher in patients who received neuraxial anesthesia. However, these two ERP components did not decrease postoperative LOS. To optimize the postoperative management of NB patients, postoperative NGTs should be avoided, while the benefit of neuraxial anesthesia is less clear as it necessitates the placement of a urinary catheter without decreasing opioid utilization.

An Algorithm to Assess Guideline Concordance of Antibiotic Choice in Community-Acquired Pneumonia.

BACKGROUND AND OBJECTIVE: This study aimed to develop and evaluate an algorithm to reduce the chart review burden of improvement efforts by automatically labeling antibiotic selection as either guideline-concordant or -discordant based on electronic health record data for patients with community-acquired pneumonia (CAP). METHODS: We developed a 3-part algorithm using structured and unstructured data to assess adherence to an institutional CAP clinical practice guideline. The algorithm was applied to retrospective data for patients seen with CAP from 2017 to 2019 at a tertiary children's hospital. Performance metrics included positive predictive value (precision), sensitivity (recall), and F1 score (harmonized mean), with macro-weighted averages. Two physician reviewers independently assigned "actual" labels based on manual chart review. RESULTS: Of 1345 patients with CAP, 893 were included in the training cohort and 452 in the validation cohort. Overall, the model correctly labeled 435 of 452 (96%) patients. Of the 286 patients who met guideline inclusion criteria, 193 (68%) were labeled as having received guideline-concordant antibiotics, 48 (17%) were labeled as likely in a scenario in which deviation from the clinical practice guideline was appropriate, and 45 (16%) were given the final label of "possibly discordant, needs review." The sensitivity was 0.96, the positive predictive value was 0.97, and the F1 was 0.96. CONCLUSIONS: An automated algorithm that uses structured and unstructured electronic health record data can accurately assess the guideline concordance of antibiotic selection for CAP. This tool has the potential to improve the efficiency of improvement efforts by reducing the manual chart review needed for quality measurement.

Comparison of postoperative pain between transoral and conventional thyroidectomy: a propensity score-matched analysis.

BACKGROUND: The extent of postoperative pain following transoral thyroidectomy is not well-understood and remains a subject of debate. This study aims to analyze and compare postoperative pain levels between patients undergoing transoral and conventional transcervical thyroidectomy. METHODS: A prospective evaluation on postoperative pain was conducted in 310 patients undergoing conventional thyroidectomy and 194 undergoing transoral thyroidectomy. Pain levels were evaluated using the numerical rating scale (NRS, ranging from 0 to 10) through preoperative and postoperative questionnaires at specified time points: 1, 3, and 6 days, and 1 and 3 months following surgery. Propensity score-matched analysis was carried out based on six covariates: sex, age, body mass index, extent of thyroidectomy, tumor size, and central neck dissection. RESULTS: After propensity score matching based on the six covariates, 121 patient pairs were identified from each group. Within this matched cohort, postoperative pain scores significantly worsened 1 day after surgery but showed progressive recovery up to 3 months post-surgery in both groups. The transoral group exhibited higher postoperative pain scores than the conventional group from day 1 (4.43 ± 2.6 vs. 3.11 ± 2.5, p < 0.001) to day 6 (1.76 ± 1.9 vs. 1.13 ± 1.6, p = 0.016) post-surgery, with no significant difference noted at 1 month. Among transoral procedures, pain scores were significantly higher for the endoscopic approach compared to the robotic approach on days 1 (5.52 ± 2.3 vs. 4.29 ± 2.3, p = 0.028) and 3 (3.52 ± 2.5 vs. 2.64 ± 2.0, p = 0.047) post-surgery. CONCLUSIONS: Postoperative pain was significantly higher in transoral thyroidectomy compared to conventional thyroidectomy up to 6 days post-surgery. Within the transoral group, the robotic procedure resulted in lower pain levels than the endoscopic approach during the early postoperative period.

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils.

The structural maintenance of chromosomes (SMC) protein complexes-cohesin, condensin, and the Smc5/6 complex (Smc5/6)-are essential for chromosome function. At the molecular level, these complexes fold DNA by loop extrusion. Accordingly, cohesin creates chromosome loops in interphase, and condensin compacts mitotic chromosomes. However, the role of Smc5/6's recently discovered DNA loop extrusion activity is unknown. Here, we uncover that Smc5/6 associates with transcription-induced positively supercoiled DNA at cohesin-dependent loop boundaries on budding yeast (Saccharomyces cerevisiae) chromosomes. Mechanistically, single-molecule imaging reveals that dimers of Smc5/6 specifically recognize the tip of positively supercoiled DNA plectonemes and efficiently initiate loop extrusion to gather the supercoiled DNA into a large plectonemic loop. Finally, Hi-C analysis shows that Smc5/6 links chromosomal regions containing transcription-induced positive supercoiling in cis. Altogether, our findings indicate that Smc5/6 controls the three-dimensional organization of chromosomes by recognizing and initiating loop extrusion on positively supercoiled DNA.

Eighth Cervical Nerve Root Block During Interscalene Brachial Plexus Block Decreases Pain Caused by Posterior Portal Placement but Increases Horner Syndrome in Patients Undergoing Arthroscopic Shoulder Surgery: A Randomized Controlled Trial.

PURPOSE: To compare the intensity of pain on posterior portal placement between a C5-C7 root block (conventional interscalene brachial plexus block [ISBPB]) and a C5-C8 root block in patients undergoing arthroscopic shoulder surgery. METHODS: In this prospective, single-blinded, parallel-group randomized controlled trial, patients were randomized to receive either a C5-C7 root block (C5-C7 group, n = 37) or a C5-C8 root block (C5-C8 group, n = 36) with 25 mL of 0.75% ropivacaine. The primary outcome was the pain intensity on posterior portal placement, which was graded as 0 (no pain), 1 (mild pain), or 2 (severe pain). The secondary outcomes were the bilateral pupil diameters measured 30 minutes after ISBPB placement; the incidence of Horner syndrome, defined as a difference in pupil diameter (ipsilateral - contralateral) of less than -0.5 mm; the onset of postoperative pain; and the postoperative numerical rating pain score, where 0 and 10 represent no pain and the worst pain imaginable, respectively. RESULTS: Fewer patients reported mild or severe pain on posterior portal placement in the C5-C8 group than in the C5-C7 group (9 of 36 [25.0%] vs 24 of 37 [64.9%], P = .003). Less pain on posterior portal placement was reported in the C5-C8 group than in the C5-C7 group (median [interquartile range], 0 [0-0.75] vs 1 [0-1]; median difference [95% confidence interval], 1 [0-1]; P = .001). The incidence of Horner syndrome was higher in the C5-C8 group than in the C5-C7 group (33 of 36 [91.7%] vs 22 of 37 [59.5%], P = .001). No significant differences in postoperative numerical rating pain scores and onset of postoperative pain were found between the 2 groups. CONCLUSIONS: A C5-C8 root block during an ISBPB reduces the pain intensity on posterior portal placement. However, it increases the incidence of Horner syndrome with no improvement in postoperative pain compared with the conventional ISBPB (C5-C7 root block). LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Comparison of Outcomes Between Surveillance Ultrasound and Completion Lymph Node Dissection in Children and Adolescents With Sentinel Lymph Node-Positive Cutaneous Melanoma.

OBJECTIVE: To determine the impact of nodal basin ultrasound (US) surveillance versus completion lymph node dissection (CLND) in children and adolescents with sentinel lymph node (SLN) positive melanoma. BACKGROUND: Treatment for children and adolescents with melanoma are extrapolated from adult trials. However, there is increasing evidence that important clinical and biological differences exist between pediatric and adult melanoma. METHODS: Patients ≤18 years diagnosed with cutaneous melanoma between 2010 and 2020 from 14 pediatric hospitals were included. Data extracted included demographics, histopathology, nodal basin strategies, surveillance intervals, and survival information. RESULTS: Of 252 patients, 90.1% (n=227) underwent SLN biopsy (SLNB), 50.9% (n=115) had at least 1 positive node. A total of 67 patients underwent CLND with 97.0% (n=65/67) performed after a positive SLNB. In contrast, 46 total patients underwent US observation of nodal basins with 78.3% (n=36/46) of these occurring after positive SLNB. Younger patients were more likely to undergo US surveillance (median age 8.5 y) than CLND (median age 11.3 y; P =0.0103). Overall, 8.9% (n=21/235) experienced disease recurrence: 6 primary, 6 nodal, and 9 distant. There was no difference in recurrence (11.1% vs 18.8%; P =0.28) or death from disease (2.2% vs 9.7%; P =0.36) for those who underwent US versus CLND, respectively. CONCLUSIONS: Children and adolescents with cutaneous melanoma frequently have nodal metastases identified by SLN. Recurrence was more common among patients with thicker primary lesions and positive SLN. No significant differences in oncologic outcomes were observed with US surveillance and CLND following the identification of a positive SLN.