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OBJECTIVE: To describe the impact of lack of workplace support (LOWS) for obstetric health on surgeon distress and career satisfaction. BACKGROUND: Although most pregnant surgeons desire clinical duty reductions to mitigate obstetric risk, few modify their schedules due to low workplace support. METHODS: US surgeons with at least one live birth completed an electronic survey. LOWS during pregnancy was defined as (1) disagreeing that colleagues/leadership were supportive of obstetric-mandated bedrest; (2) feeling unable to reduce clinical duties despite health concerns due to risk of financial penalties, requirement to make up missed call shifts, being perceived as "weak", burdening colleagues, or accommodations being denied by the workplace. Multivariate logistic regression determined the association between LOWS and burnout, low quality of life, plans to leave clinical practice or to reduce work hours, and likelihood of recommending a surgical career to one's child. RESULTS: Of 557 surgeons, the 360 (64.6%) who reported LOWS during pregnancy were more likely to report burnout (OR:2.57; 95%CI:1.60-4.13), low quality of life (OR:1.57; 95%CI:1.02-2.41), a desire to leave their practice (OR:2.74; 95%CI: 1.36-5.49), plans to reduce clinical hours in the next year (OR:4.25; 95%CI:1.82-9.90), and were less likely to recommend their career to their child (OR:0.44; 95%CI:0.28-0.70). CONCLUSIONS: LOWS for maternal-fetal health concerns is associated with burnout, low quality of life, and career dissatisfaction. The work environment is a modifiable factor requiring system-level interventions to limit clinical work during pregnancy and provide fair compensation for covering surgeons. Supporting surgeons during pregnancy is a short-term investment with long-term implications for improving longevity and diversity of the workforce.
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Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.
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Esclerosis Amiotrófica Lateral , Modelos Animales de Enfermedad , Electromiografía , Dispositivos Electrónicos Vestibles , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Animales , Electromiografía/métodos , Evaluación Preclínica de Medicamentos , Trastornos de Deglución/fisiopatología , Trastornos de Deglución/etiología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Músculo Esquelético/inervación , Humanos , Masculino , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/fisiología , RatasRESUMEN
Primary encephaloceles are congenital mesodermal defects that result in brain tissue protruding through the skull. These defects most commonly occur occipitally but can be present anywhere in the calvarium. Meningoencephaloceles are a subclassification that includes herniation of the meninges. Basal meningoencephaloceles with cleft palate defects are the rarest form, with very few reports discussing anesthetic implications. We report a case of a giant basal meningoencephalocele that involves the nasal and oral cavities with a risk of thecal sac rupture.
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Encefalocele , Meningocele , Humanos , Encefalocele/cirugía , Recién Nacido , Meningocele/cirugía , Masculino , FemeninoRESUMEN
Importance: The ability to pursue family planning goals is integral to gender equity in any field. Procedural specialties pose occupational risks to pregnancy. As the largest procedural specialty, general surgery provides an opportunity to understand family planning, workplace support for parenthood, obstetric outcomes, and the impact of these factors on workforce well-being, gender equity, and attrition. Objective: To examine pregnancy and parenthood experiences, including mistreatment and obstetric outcomes, among a cohort of US general surgical residents. Design, Setting, and Participants: This cohort study involved a cross-sectional national survey of general surgery residents in all programs accredited by the Accreditation Council for Graduate Medical Education after the 2021 American Board of Surgery In-Training Examination. Female respondents who reported a pregnancy and male respondents whose partners were pregnant during clinical training were queried about pregnancy- and parenthood-based mistreatment, obstetric outcomes, and current well-being (burnout, thoughts of attrition, suicidality). Main Outcomes and Measures: Primary outcomes included obstetric complications and postpartum depression compared between female residents and partners of male residents. Secondary outcomes included perceptions about support for family planning, pregnancy, or parenthood; assisted reproductive technology use; pregnancy/parenthood-based mistreatment; neonatal complications; and well-being, compared between female and male residents. Results: A total of 5692 residents from 325 US general surgery programs participated (81.2% response rate). Among them, 957 residents (16.8%) reported a pregnancy during clinical training (692/3097 [22.3%] male vs 265/2595 [10.2%] female; P < .001). Compared with male residents, female residents more frequently delayed having children because of training (1201/2568 [46.8%] females vs 1006/3072 [32.7%] males; P < .001) and experienced pregnancy/parenthood-based mistreatment (132 [58.1%] females vs 179 [30.5%] males; P < .001). Compared with partners of male residents, female residents were more likely to experience obstetric complications (odds ratio [OR], 1.42; 95% CI, 1.04-1.96) and postpartum depression (OR, 1.63; 95% CI, 1.11-2.40). Pregnancy/parenthood-based mistreatment was associated with increased burnout (OR, 2.03; 95% CI, 1.48-2.78) and thoughts of attrition (OR, 2.50; 95% CI, 1.61-3.88). Postpartum depression, whether in female residents or partners of male residents, was associated with resident burnout (OR, 1.93; 95% CI, 1.27-2.92), thoughts of attrition (OR, 2.32; 95% CI, 1.36-3.96), and suicidality (OR, 5.58; 95% CI, 2.59-11.99). Conclusions and Relevance: This study found that pregnancy/parenthood-based mistreatment, obstetric complications, and postpartum depression were associated with female gender, likely driving gendered attrition. Systematic change is needed to protect maternal-fetal health and advance gender equity in procedural fields.
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INTRODUCTION: Evidence suggests that coronavirus disease of 2019 (COVID-19) infection is associated with increased perioperative mortality in adults. We hypothesized that children with COVID-19 had worse outcomes after emergency surgery compared to children without COVID-19. METHODS: Children <18 y who underwent emergency abdominal surgery were included in the 2021 National Surgical Quality Improvement Program-Pediatric database. Children with COVID-19 diagnosed preoperatively were identified. A propensity score-matched analysis was performed, matching demographic and clinical factors. Postoperative morbidity and mortality were assessed. Due to event rarity, a composite outcome for postoperative morbidity was also assessed. Chi-square and Mann-Whitney U tests identified differences between groups. Logistic regression identified the odds of the composite morbidity outcome. RESULTS: Overall, 13,619 children (median age 10.8 y, interquartile range: 6.4-14.2) underwent emergency abdominal surgery, of whom 224 (1.6%) had COVID-19. The majority were female (58.2%), White (61.3%), and non-Hispanic (53.4%). On unadjusted analysis, there was an association between COVID-19 status and American Society of Anesthesiologists classification (P < 0.01). A greater proportion of COVID-19-positive children had dirty/infected wounds (30.4% versus 22.2%, P < 0.01). Also, a greater proportion of COVID-19-positive children suffered cardiac arrest requiring cardiopulmonary resuscitation (1.3% versus 0.2%, P < 0.01). Matched cohorts of 224 COVID-19-positive and 224 COVID-19-negative children did not differ by demographic or clinical factors (P > 0.05). Propensity score matching did not reveal significant differences in postoperative morbidity or mortality. Children with COVID-19 did not demonstrate increased odds of morbidity analyzed as a composite outcome (odds ratio: 0.65, 95% confidence interval: 0.29-1.48, P = 0.31). CONCLUSIONS: Contrary to findings in adults, COVID-19 was not associated with worse clinical outcomes in children undergoing emergency abdominal surgery.
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BACKGROUND AND AIMS: The Chinese visceral adipose index (CVAI) is more significantly associated with cardiometabolic risk factors than other obesity indices. This study investigated the relationship between CVAI and left ventricular (LV) remodeling. METHODS AND RESULTS: This study included 75,132 Koreans who underwent echocardiography during a health checkup. They were grouped according to quartile levels of the CVAI, body mass index (BMI), waist circumference (WC), and visceral adiposity index (VAI). LV remodeling was defined as the presence of abnormal relative wall thickness (ARWT) and left ventricular hypertrophy (LVH). Multivariate adjusted logistic regression analysis (adjusted OR [95% confidence interval]) was used to analyze the association between ARWT and LVH according to the quartile levels of each index. Receiver operating characteristic (ROC) graphs and areas under the curve (AUC) were calculated to identify the predictive ability of the indices for ARWT and LVH. ARWT was associated proportionally with CVAI quartiles in both men (second quartile: 1.42 [1.29-1.56], third quartile: 1.61 [1.46-1.77], fourth quartile: 2.01 [1.84-2.21]), and women (second quartile: 1.06 [0.78-1.45], third quartile: 1.15 [0.86-1.55], and fourth quartile: 2.09 [1.56-2.80]). LVH was significantly associated with third (1.74 [1.07-2.83]) and fourth quartile (1.94 [1.18-3.20]) groups of CVAI in women. ROC and AUC analyses indicated that CVAI was superior to other indices in predicting ARWT in men and LVH and ARWT in women. CONCLUSION: The CVAI is an effective surrogate marker of LV remodeling, particularly in women.
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BACKGROUND: Posterior spinal fusion (PSF) and hip reconstruction are commonly indicated surgeries in children with cerebral palsy (CP), particularly those functioning at GMFCS levels IV and V. These are large and often painful procedures, and previous literature suggests that hip surgery is more painful than spine surgery in this patient population. The purpose of this study is to investigate pain scores and opioid use following hip and spine surgery in a large cohort of children with CP, including many patients who have undergone both types of surgery. METHODS: A retrospective chart review was performed to identify children with CP who underwent hip reconstruction and/or PSF at a tertiary children's hospital between 2004 and 2022. Charts were reviewed for demographic data, pain scores, pain medication usage, duration of hospital stay, and complications. RESULTS: Data were collected for 200 patients (101 male, 99 female) who met inclusion criteria. Eighty-seven patients underwent hip reconstruction, 62 spinal fusion, and 51 both hip and spine surgery asynchronously. Median (interquartile range) age at the time of surgery was significantly older for spinal fusion compared with hip surgery [13.1 (4.9) vs. 8.1 (5.7) y, P<0.0001]. Length of stay was significantly longer after PSF, with a median of 6 (4) days compared with 2 (1) days after hip surgery (P<0.0001). Both maximum and average daily pain scores were similar following hip and spine surgery, with the exception that average pain scores for hip surgery were slightly higher on postoperative day 1, hip=1.73 vs. spine=1.0 (P<0.0001). The amount of opioids used, expressed as morphine milligram equivalents (MME)/kg were similar in the hip and spine surgery groups; however, it was significantly lower in the hip surgery group on postoperative day 0, hip=0.06 versus spine=0.17 (P<0.0001). For the 51 patients who underwent both hip and spine surgery, the amount of opioids used mirrored that for the entire group (similar MME/kg, though only statistically significantly less on POD 0 and 3), and pain scores were not significantly different between the 2 groups except in 2 circumstances. The 2 exceptions in these 51 patients both demonstrated lower pain scores in patients after hip surgery, including lower maximum pain scores on POD 1 (P=0.041), and lower average pain scores on POD3 (P=0.043). CONCLUSIONS: This is the largest series to date comparing postoperative pain in children with CP after hip and spine surgery, including 51 of 200 patients who underwent both types of surgery. The results of this study demonstrate that hip surgery is not more painful than spine surgery in children with CP, and conflict with the traditional belief that hip surgery is more painful. This is important information for health care providers when counseling patients and families regarding these surgeries in children with CP. LEVEL OF EVIDENCE: Level 3.
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BACKGROUND: The majority of adolescents undergoing surgery report unused prescription opioids after surgery, increasing the risk of diversion, misuse, and addiction. Adult studies have demonstrated that opioid use 24 hours before discharge corresponds with opioid use at home. We hypothesized that inpatient opioid consumption is associated with outpatient opioid use in adolescents. METHODS: Adolescents aged 13-20 years undergoing elective surgery associated with an opioid prescription were prospectively recruited. Parent-adolescent dyads were surveyed preoperatively to assess sociodemographics, health literacy, and baseline substance use, and opioid use was measured at 30- and 90-days postoperatively. Medical records were reviewed to calculate cumulative opioid use during hospitalization. Inpatient and postoperative opioid use was converted to oral morphine equivalents. Adjusting for age, sex, race, health literacy, alcohol use, pain score, and surgery, multivariable linear regression identified factors associated with outpatient oral morphine equivalent use 90 days postoperatively. RESULTS: Overall, 103 adolescents were enrolled. Median oral morphine equivalents used from 24 and 48 hours before discharge and throughout the hospitalization were 30.8 (interquartile range:11.7-45.0), 67.5 (interquartile range:37.5-94.3), and 97.5 (interquartile range:18.0-152.7), respectively. Regression analysis demonstrated that adolescent-reported pain at discharge (P = .028) and cumulative oral morphine equivalents used 24 hours (P < .001) and 48 hours (P = .003) before discharge were significantly associated with postoperative oral morphine equivalents use at home. Oral morphine equivalents consumption 24 hours before discharge estimated cumulative oral morphine equivalents use 90 days postoperatively at a 1-to-5 ratio in 94.1% of patients. CONCLUSION: For adolescents undergoing surgery, patient-reported pain at discharge and oral morphine equivalents administered 24 hours before discharge are associated with cumulative outpatient opioid use. Tailoring outpatient prescriptions to total oral morphine equivalent consumption 24 hours before discharge could reduce excess opioid prescribing.
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Analgésicos Opioides , Dolor Postoperatorio , Alta del Paciente , Humanos , Adolescente , Femenino , Masculino , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Adulto Joven , Estudios Prospectivos , Procedimientos Quirúrgicos Electivos/efectos adversos , Pacientes Ambulatorios/estadística & datos numéricosRESUMEN
BACKGROUND: Despite high smoking rate in people with depressive symptoms, there is ongoing debate about relationship between smoking and depressive symptoms. METHODS: Study participants were 57,441 Korean men. We collected their baseline data between 2011 and 2012, and conducted follow-up from 2013 to 2019. They were categorized by smoking status (never: < 100 cigarettes smoking in life time, former: currently quitting smoking, and current smoker: currently smoking), smoking amount (pack/day and pack-year) and urine cotinine excretion. The development of depressive symptoms was determined in CES-D score ≥ 16. Cox proportional hazards model was used to analyze the multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CI) for depressive symptoms in relation to smoking status, smoking amount, and urine cotinine excretion. RESULTS: During 6.7 years of median follow-up, the risk of depressive symptoms increased in order of never (reference), former (HR = 1.08, 95% CI: 1.01-1.15) and current smoker (HR = 1.24, 95% CI: 1.16-1.32). Among current smoker, the risk of depressive symptoms increased proportionally to daily smoking amount (< 1 pack; HR = 1.21, 95% CI: 1.13-1.29, and ≥ 1 pack; HR = 1.34, 95% CI: 1.23 - 1.45). This pattern of relationship was consistently observed for pack-year in former smoker and current smoker. Additionally, urine cotinine excretion was proportionally associated with the risk of depressive symptoms. CONCLUSION: Exposure to smoking was associated with the increased risk of depressive symptoms. Dose dependent relationship was observed between smoking amount and the risk of depressive symptoms.
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Cotinina , Depresión , Fumar , Humanos , Masculino , Depresión/epidemiología , República de Corea/epidemiología , Adulto , Persona de Mediana Edad , Cotinina/orina , Estudios Longitudinales , Fumar/epidemiología , Fumar/efectos adversos , Factores de Riesgo , Modelos de Riesgos ProporcionalesRESUMEN
Rationale: Standardized dosing of antitubercular 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 assays that predict metabolism of antitubercular drugs have been lacking. Objectives: We sought to develop a Nanopore sequencing panel and validate its performance in patients with active tuberculosis (TB) to personalize treatment dosing. Methods: We developed a Nanopore sequencing panel targeting 15 SNPs in five genes affecting the metabolism of antitubercular drugs. For validation, we sequenced DNA samples (n = 48) from the 1,000 Genomes Project and compared the variant calling accuracy with that of 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 isoniazid (INH) and rifampin (RIF). Measurements and Main Results: The pharmacogenomic panel achieved 100% concordance with Illumina sequencing in variant identification for the samples from the 1,000 Genomes Project. In the clinical cohort, coverage was more than 100× for 1,498 of 1,500 (99.8%) amplicons across the 100 samples. Thirty-three percent, 47%, and 20% of participants were identified as slow, intermediate, and rapid INH acetylators, respectively. INH clearance was 2.2 times higher among intermediate acetylators and 3.8 times higher among rapid acetylators, compared with slow acetylators (P < 0.0001). RIF clearance was 17.3% (2.50-29.9) lower in individuals with homozygous AADAC rs1803155 GâA substitutions (P = 0.0015). Conclusions: Targeted sequencing can enable the detection of polymorphisms that influence TB drug metabolism on a low-cost, portable instrument to personalize dosing for TB treatment or prevention.
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Antituberculosos , Secuenciación de Nanoporos , Polimorfismo de Nucleótido Simple , Tuberculosis , Humanos , Antituberculosos/uso terapéutico , Antituberculosos/farmacocinética , Femenino , Masculino , Adulto , Tuberculosis/tratamiento farmacológico , Tuberculosis/genética , Secuenciación de Nanoporos/métodos , Polimorfismo de Nucleótido Simple/genética , Persona de Mediana Edad , Medicina de Precisión/métodos , Isoniazida/uso terapéutico , Isoniazida/farmacocinética , Rifampin , Pruebas de Farmacogenómica/métodos , Farmacogenética/métodos , Sudáfrica , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: Sleep is essential for postoperative recovery. Prescription opioid can be associated with disordered sleep. There is little research on sleep patterns among adolescents using opioids for postoperative pain. Our objective was to identify factors associated with disordered sleep among adolescents undergoing surgery. METHODS: Prospective single-center survey-based cohort study of adolescents (13-20y) undergoing eight surgeries commonly associated with an opioid prescription. Participants completed a preoperative survey measuring clinical, mental health, and sociodemographic factors, and postoperative surveys at 30- and 90-days. All surveys administered the Sleep Problems Questionnaire. Repeated measures logistic regression evaluated the impact of surgery on worsening postoperative sleep scores. Linear change model evaluated sleep score trajectories; Poisson regression identified the impact of preoperative disordered sleep on opioid use. RESULTS: Overall, 167 adolescents (median 15y, 64% female) were included. Twenty-seven (16.2%) reported disordered sleep preoperatively and 41 (24.6%) postoperatively. Prescription opioid use was not associated with development of disordered sleep postoperatively (OR:1.33; 95% CI:0.38-4.68). Adolescents were 2.20 (95% CI:1.42-3.40) times more likely to report disordered sleep postoperatively. Preoperative disordered sleep, time after surgery, and mental health comorbidities were associated with worsening postoperative sleep score trajectories (p < 0.01). Adolescents with preoperative disordered sleep were not more likely to use opioids (OR:2.56, 95% CI:0.76-8.63, p = 0.13) nor did they use more pills (IRR:0.84, 95% CI:0.62-1.15, p = 0.27). CONCLUSIONS: Adolescents were more likely to report disordered sleep postoperatively. Preoperative disordered sleep and mental health comorbidities, but not prescription opioid use, were associated with worsening sleep after surgery. Future efforts to improve adolescent postoperative sleep should address baseline disordered sleep and mental health comorbidities. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Prospective cohort study.
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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.
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Regulación Neoplásica de la Expresión Génica , Ratones Endogámicos NOD , Ratones SCID , Neuroblastoma , Animales , Neuroblastoma/patología , Neuroblastoma/genética , Neuroblastoma/metabolismo , Humanos , Ratones , Línea Celular Tumoral , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias de la Médula Ósea/secundario , Neoplasias de la Médula Ósea/genética , Perfilación de la Expresión Génica , TranscriptomaRESUMEN
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.
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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.
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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.
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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.
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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.
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Proteínas Sanguíneas , Cistadenocarcinoma Seroso , Galectina 3 , Neoplasias Uterinas , Humanos , Femenino , Neoplasias Uterinas/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Galectina 3/genética , Galectina 3/metabolismo , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Proliferación Celular , Línea Celular Tumoral , Pronóstico , Animales , Ratones , Galectinas/genética , Galectinas/metabolismo , Movimiento CelularRESUMEN
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.
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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.
Asunto(s)
Perforación Intestinal , Estomas Quirúrgicos , Herida Quirúrgica , Infección de Heridas , Humanos , Recién Nacido , Preescolar , Adulto , Perforación Intestinal/cirugía , Constricción Patológica , Complicaciones Posoperatorias , Estudios Retrospectivos , ProlapsoRESUMEN
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.