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BACKGROUND: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined. OBJECTIVE: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population. METHODS: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics. RESULTS: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05). CONCLUSIONS: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.
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Neoplasias Colorrectales , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Mutación , Neoplasias Peritoneales , Proteínas Proto-Oncogénicas p21(ras) , Proteína p53 Supresora de Tumor , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Femenino , Masculino , Estudios Retrospectivos , Proteínas Proto-Oncogénicas p21(ras)/genética , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/genética , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/genética , Pronóstico , Tasa de Supervivencia , Terapia Combinada , Estudios de Seguimiento , Anciano , Biomarcadores de Tumor/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , AdultoRESUMEN
BACKGROUND: While cholecystectomy is one of the most common operations performed in the United States, there is a continued debate regarding its prophylactic role in elective surgery. Particularly among patients with peritoneal carcinomatosis who undergo cytoreduction surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), further abdominal operations may pose increasing morbidity due to intraabdominal adhesions and potential recurrence. This bi-institutional retrospective study aims to assess postoperative morbidity associated with prophylactic cholecystectomy at the time of CRS-HIPEC. METHODS: We performed a bi-institutional retrospective analysis of 578 patients who underwent CRS-HIPEC from 2011 to 2021. Postoperative outcomes among patients who underwent prophylactic cholecystectomy at the time of CRS-HIPEC were compared to patients who did not, particularly rate of bile leak, hospital length of stay, rate of Clavien-Dindo classification morbidity grade III or greater, and number of hospital re-admissions within 30 days. RESULTS: Of the 535 patients available for analysis, 206 patients (38.3%) underwent a prophylactic cholecystectomy. Of the 3 bile leaks (1.5%) that occurred among patients who underwent prophylactic cholecystectomy, all 3 occurred in patients who underwent a concomitant liver resection. There were no significant differences in hospital length of stay, postoperative morbidity, and number of hospital re-admissions among patients who underwent prophylactic cholecystectomy compared to those who did not. CONCLUSION: Prophylactic cholecystectomy in patients undergoing CRS-HIPEC is not associated with increased morbidity or increased bile leak risk compared to historical data. While the benefits of prophylactic cholecystectomy are not yet elucidated, it may be considered to avoid potential future morbid operations for biliary disease.
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Colecistectomía , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Persona de Mediana Edad , Neoplasias Peritoneales/terapia , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Adulto , Tiempo de Internación/estadística & datos numéricos , Anciano , Terapia CombinadaRESUMEN
Importance: Gangrenous, suppurative, and exudative (GSE) findings have been associated with increased surgical site infection (SSI) risk and resource use in children with nonperforated appendicitis. Establishing the role for postoperative antibiotics may have important implications for infection prevention and antimicrobial stewardship. Objective: To compare SSI rates in children with nonperforated appendicitis with GSE findings who did and did not receive postoperative antibiotics. Design, Setting, and Participants: This was a retrospective cohort study using American College of Surgeons' National Surgical Quality Improvement Program (NSQIP)-Pediatric Appendectomy Targeted data from 16 hospitals participating in a regional research consortium. NSQIP data were augmented with operative report and antibiotic use data obtained through supplemental medical record review. Children with nonperforated appendicitis with GSE findings who underwent appendectomy between July 1, 2015, and June 30, 2020, were identified using previously validated intraoperative criteria. Data were analyzed from October 2022 to July 2023. Exposure: Continuation of antibiotics after appendectomy. Main Outcomes and Measures: Rate of 30-day postoperative SSI including both incisional and organ space infections. Complementary hospital and patient-level analyses were conducted to explore the association between postoperative antibiotic use and severity-adjusted outcomes. The hospital-level analysis explored the correlation between postoperative antibiotic use and observed to expected (O/E) SSI rate ratios after adjusting for differences in disease severity (presence of gangrene and postoperative length of stay) among hospital populations. In the patient-level analysis, propensity score matching was used to balance groups on disease severity, and outcomes were compared using mixed-effects logistic regression to adjust for hospital-level clustering. Results: A total of 958 children (mean [SD] age, 10.7 [3.7] years; 567 male [59.2%]) were included in the hospital-level analysis, of which 573 (59.8%) received postoperative antibiotics. No correlation was found between hospital-level SSI O/E ratios and postoperative antibiotic use when analyzed by either overall rate of use (hospital median, 53.6%; range, 31.6%-100%; Spearman ρ = -0.10; P = .71) or by postoperative antibiotic duration (hospital median, 1 day; range, 0-7 days; Spearman ρ = -0.07; P = .79). In the propensity-matched patient-level analysis including 404 patients, children who received postoperative antibiotics had similar rates of SSI compared with children who did not receive postoperative antibiotics (3 of 202 [1.5%] vs 4 of 202 [2.0%]; odds ratio, 0.75; 95% CI, 0.16-3.39; P = .70). Conclusions and Relevance: Use of postoperative antibiotics did not improve outcomes in children with nonperforated appendicitis with gangrenous, suppurative, or exudative findings.
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Antibacterianos , Apendicectomía , Apendicitis , Gangrena , Infección de la Herida Quirúrgica , Adolescente , Niño , Femenino , Humanos , Masculino , Antibacterianos/uso terapéutico , Apendicitis/cirugía , Cuidados Posoperatorios , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiologíaRESUMEN
OBJECTIVE: To develop a severity-adjusted, hospital-level benchmarking comparative performance report for postoperative organ space infection and antibiotic utilization in children with complicated appendicitis. BACKGROUND: No benchmarking data exist to aid hospitals in identifying and prioritizing opportunities for infection prevention or antimicrobial stewardship in children with complicated appendicitis. METHODS: This was a multicenter cohort study using NSQIP-Pediatric data from 16 hospitals participating in a regional research consortium, augmented with antibiotic utilization data obtained through supplemental chart review. Children with complicated appendicitis who underwent appendectomy from 07/01/2015 to 06/30/2020 were included. Thirty-day postoperative OSI rates and cumulative antibiotic utilization were compared between hospitals using observed-to-expected (O/E) ratios after adjusting for disease severity using mixed effects models. Hospitals were considered outliers if the 95% confidence interval for O/E ratios did not include 1.0. RESULTS: 1790 patients were included. Overall, the OSI rate was 15.6% (hospital range: 2.6-39.4%) and median cumulative antibiotic utilization was 9.0 days (range: 3.0-13.0). Across hospitals, adjusted O/E ratios ranged 5.7-fold for OSI (0.49-2.80, P=0.03) and 2.4-fold for antibiotic utilization (0.59-1.45, P<0.01). Three (19%) hospitals were outliers for OSI (1 high and 2 low performers), and eight (50%) were outliers for antibiotic utilization (5 high and 3 low utilizers). Ten (63%) hospitals were identified as outliers in one or both measures. CONCLUSIONS: A comparative performance benchmarking report may help hospitals identify and prioritize quality improvement opportunities for infection prevention and antimicrobial stewardship, as well as identify exemplar performers for dissemination of best practices.
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OBJECTIVE: To compare rates of postoperative drainage and culture profiles in children with complicated appendicitis treated with the two most common antibiotic regimens with and without antipseudomonal activity (piperacillin-tazobactam [PT] and ceftriaxone with metronidazole [CM]). SUMMARY OF BACKGROUND DATA: Variation in use of antipseudomonal antibiotics has been driven by a paucity of multicenter data reporting clinically relevant, culture-based outcomes. METHODS: Retrospective cohort study of patients with complicated appendicitis (7/2015-6/2020) using NSQIP-Pediatric data from 15 hospitals participating in a regional research consortium. Operative report details, antibiotic utilization, and culture data were obtained through supplemental chart review. Rates of 30-day postoperative drainage and organism-specific culture positivity were compared between groups using mixed effects regression to adjust for clustering after propensity matching on measures of disease severity. RESULTS: 1002 children met criteria for matching (58.9% received CM and 41.1% received PT). In the matched sample of 778 patients, children treated with PT had similar rates of drainage overall (PT: 11.8%, CM: 12.1%; OR 1.44 [OR:0.71-2.94]) and higher rates of drainage associated with growth of any organism (PT: 7.7%, CM: 4.6%; OR 2.41 [95%CI:1.08-5.39]) and Escherichia coli (PT: 4.6%, CM: 1.8%; OR 3.42 [95%CI:1.07-10.92]) compared to treatment with CM. Rates were similar between groups for drainage associated with multiple organisms (PT: 2.6%, CM: 1.5%; OR 3.81 [95%CI:0.96-15.08]) and Pseudomonas (PT: 1.0%, CM: 1.3%; OR 3.42 [95%CI:0.55-21.28]). CONCLUSIONS AND RELEVANCE: Use of antipseudomonal antibiotics is not associated with lower rates of postoperative drainage procedures or more favorable culture profiles in children with complicated appendicitis.
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BACKGROUND: The objective was to explore the hospital-level relationship between routine pre-discharge WBC utilization (RPD-WBC) and outcomes in children with complicated appendicitis. METHODS: Multicenter analysis of NSQIP-Pediatric data from 14 consortium hospitals augmented with RPD-WBC data. WBC were considered routine if obtained within one day of discharge in children who did not develop an organ space infection (OSI) or fever during the index admission. Hospital-level observed-to-expected ratios (O/E) for 30-day outcomes (antibiotic days, imaging utilization, healthcare days, and OSI) were calculated after adjusting for appendicitis severity and patient characteristics. Spearman correlation was used to explore the relationship between hospital-level RPD-WBC utilization and O/E's for each outcome. RESULTS: 1528 children were included. Significant variation was found across hospitals in RPD-WBC use (range: 0.7-100%; p < 0.01) and all outcomes (mean antibiotic days: 9.9 [O/E range: 0.56-1.44, p < 0.01]; imaging: 21.9% [O/E range: 0.40-2.75, p < 0.01]; mean healthcare visit days: 5.7 [O/E 0.74-1.27, p < 0.01]); OSI: 14.1% [O/E range: 0.43-3.64, p < 0.01]). No correlation was found between RPD-WBC use and antibiotic days (r = +0.14, p = 0.64), imaging (r = -0.07, p = 0.82), healthcare days (r = +0.35, p = 0.23) or OSI (r = -0.13, p = 0.65). CONCLUSIONS: Increased RPD-WBC utilization in pediatric complicated appendicitis did not correlate with improved outcomes or resource utilization at the hospital level. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Clinical Research.
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Apendicitis , Niño , Humanos , Apendicitis/complicaciones , Apendicitis/cirugía , Alta del Paciente , Recuento de Leucocitos , Antibacterianos/uso terapéutico , Apendicectomía/métodos , Toma de Decisiones Clínicas , Hospitales , Estudios RetrospectivosRESUMEN
BACKGROUND: Prophylactic ureteral stents (PUS) are typically placed prior to complex abdominal or pelvic operations at the surgeon's discretion to help facilitate detection of iatrogenic ureteral injury. However, its usefulness and safety in the setting of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) have not been examined. This study aims to evaluate the potential clinical value and risk profile of prophylactic ureteral stent placement prior to CRS-HIPEC. METHODS: We performed a single-institutional retrospective analysis of 145 patients who underwent CRS-HIPEC from 2013 to 2021. Demographic and operative characteristics were compared between patients who underwent PUS placement and those that did not. Ureteral stent-related complications were evaluated. RESULTS: Of the 145 patients included in the analysis, 124 underwent PUS placement. There were no significant differences in patient demographics, medical comorbidities, or tumor characteristics. Additionally, PUS placement did not significantly increase operative time and was not associated with increased pelvic organ resection. However, patients who underwent prophylactic ureteral stenting had significantly higher peritoneal carcinomatosis index score (15.1 vs 9.1, P=.002) and increased rate of ureteral complications (24.2% vs 14.3%, P=.04), which led to lengthened hospital stay (13.2 days vs 8.1 days, P= .03). Notably, the sole ureteral injury and three cases of hydronephrosis were seen in patients who underwent PUS. CONCLUSION: Prophylactic ureteral stent placement in patients undergoing CRS-HIPEC may be useful, particularly in patients with predetermined extensive pelvic disease. However, PUS placement is not without potential morbidity and should be selectively considered in patients for whom benefits outweigh the risks.
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Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Estudios Retrospectivos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/patología , Quimioterapia del Cáncer por Perfusión Regional , Stents , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tasa de SupervivenciaRESUMEN
A tracheal bronchus is a rare anatomic variant characterized by a bronchus originating from the trachea rather than the carina. These are most commonly asymptomatic and found incidentally but can cause recurrent pneumonias in children. Here, we present a case of a thoracoscopic resection of an azygous lobe with a tracheal bronchus in a 9-year-old female.
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Bronquios , Neumonía , Femenino , Niño , Humanos , Bronquios/diagnóstico por imagen , Bronquios/cirugía , Tráquea/diagnóstico por imagen , Tráquea/cirugíaRESUMEN
BACKGROUND: The primary aim of this study is to evaluate the oncologic outcomes of two popular systemic chemotherapy approaches in patients with colorectal peritoneal metastases (CPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: We performed a dual-center retrospective review of consecutive patients who underwent CRS-HIPEC for CPM due to high or intermediate-grade colorectal cancer. Patients in the total neoadjuvant therapy (TNT) group received 6 months of preoperative chemotherapy. Patients in the "sandwich" (SAND) chemotherapy group received 3 months of preoperative chemotherapy with a maximum of 3 months of postoperative chemotherapy. RESULTS: A total of 34 (43%) patients were included in the TNT group and 45 (57%) patients in the SAND group. The median overall survival (OS) in the TNT and SAND groups were 77 and 61 months, respectively (p = 0.8). Patients in the TNT group had significantly longer recurrence-free survival (RFS) than the SAND group (29 vs. 12 months, p = 0.02). In a multivariable analysis, the TNT approach was independently associated with improved RFS. CONCLUSION: In this retrospective study, a TNT approach was associated with improved RFS, but not OS when compared with a SAND approach. Further prospective studies are needed to examine these systemic chemotherapeutic approaches in patients with CPM undergoing CRS-HIPEC.
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Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Colorrectales/patología , Terapia Neoadyuvante , Neoplasias Peritoneales/secundario , Procedimientos Quirúrgicos de Citorreducción , Estudios Retrospectivos , Quimioterapia del Cáncer por Perfusión Regional , Tasa de Supervivencia , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: As surgical training shifts toward a competency-based paradigm, deliberate practice for procedures must be a point of focus. The purpose of this study was to assess the impact of an educational time-out intervention on educational experience and operative performance in endocrine surgery. METHODS: For 12 months, third-year general surgery residents used the educational time-out to establish an operative step of focus for thyroidectomy and parathyroidectomy procedures. Data were collected using the System for Improving and Measuring Procedural Learning application and post-rotation surveys. The Zwisch scale was used to classify supervision, with meaningful autonomy defined as passive help or supervision only. RESULTS: Eight residents and 3 attending surgeons performed the educational time-out for a total of 211 operations (93% completion rate). At the end of each rotation, there was improvement in the frequency of goal setting. There was strong agreement (90%) that the intervention strengthened the educational experience. For most cases (52%), the residents were rated at active help. Residents performed a median of 3/6 thyroidectomy steps at meaningful autonomy and a median of 2/5 parathyroidectomy steps at meaningful autonomy. Review of the qualitative data revealed that optimal feedback was provided in 46% of cases. CONCLUSION: The educational time-out strengthened educational experiences. Stepwise procedural data revealed the varying levels of supervision that exist within an operation. Broader implementation of this intervention could facilitate competency-based procedural education.
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Procedimientos Quirúrgicos Endocrinos , Cirugía General , Internado y Residencia , Humanos , Glándula Tiroides , Competencia Clínica , Educación de Postgrado en Medicina/métodos , Cirugía General/educaciónRESUMEN
INTRODUCTION: Many patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal adenocarcinoma peritoneal metastases (APM) undergo preoperative systemic chemotherapy. The primary aim of this study is to evaluate differences in oncologic outcomes among two popular chemotherapy approaches in patients with APM undergoing CRS-HIPEC. METHODS: We performed a multicenter retrospective review of patients who underwent CRS-HIPEC for APM due to high or intermediate grade disease between 2013 and 2019. Patients in the total neoadjuvant therapy group (TNT) received 12 cycles of preoperative chemotherapy. Patients in the "sandwich" chemotherapy group (SAND) received six cycles of preoperative chemotherapy with a maximum of six cycles of postoperative chemotherapy. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS) defined as months from date of first treatment or surgery, respectively. RESULTS: A total of 39 patients were included in this analysis, with 25 (64%) patients in the TNT group and 14 (36%) patients in the SAND group. Patients in the TNT group had a median OS of 62 mo, while median OS in the SAND group was 45 mo (P = 0.01). In addition, patients in the TNT group had significantly longer RFS compared to the SAND group (35 versus 12 mo, P = 0.03). In a multivariable analysis, TNT approach was independently associated with improved OS and RFS. CONCLUSIONS: In this multicenter retrospective analysis, a TNT approach was associated with improved overall and recurrence-free survival compared to a sandwiched chemotherapy approach in patients undergoing CRS-HIPEC for high or intermediate grade APM.
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Adenocarcinoma , Neoplasias del Apéndice , Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Estudios Retrospectivos , Neoplasias del Apéndice/terapia , Neoplasias del Apéndice/patología , Peritoneo/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción , Tasa de Supervivencia , Terapia CombinadaRESUMEN
OBJECTIVE: To evaluate whether redosing antibiotics within an hour of incision is associated with a reduction in incisional surgical site infection (iSSI) in children with appendicitis. BACKGROUND: Existing data remain conflicting as to whether children with appendicitis receiving antibiotics at diagnosis benefit from antibiotic redosing before incision. METHODS: This was a multicenter retrospective cohort study using data from the Pediatric National Surgical Quality Improvement Program augmented with antibiotic utilization and operative report data obtained though supplemental chart review. Children undergoing appendectomy at 14 hospitals participating in the Eastern Pediatric Surgery Network from July 2016 to June 2020 who received antibiotics upon diagnosis of appendicitis between 1 and 6 hours before incision were included. Multivariable logistic regression was used to compare odds of iSSI in those who were and were not redosed with antibiotics within 1 hour of incision, adjusting for patient demographics, disease severity, antibiotic agents, and hospital-level clustering of events. RESULTS: A total of 3533 children from 14 hospitals were included. Overall, 46.5% were redosed (hospital range: 1.8%-94.4%, P <0.001) and iSSI rates were similar between groups [redosed: 1.2% vs non-redosed: 1.3%; odds ratio (OR) 0.84, (95%,CI, 0.39-1.83)]. In subgroup analyses, redosing was associated with lower iSSI rates when cefoxitin was used as the initial antibiotic (redosed: 1.0% vs nonredosed: 2.5%; OR: 0.38, (95% CI, 0.17-0.84)], but no benefit was found with other antibiotic regimens, longer periods between initial antibiotic administration and incision, or with increased disease severity. CONCLUSIONS: Redosing of antibiotics within 1 hour of incision in children who received their initial dose within 6 hours of incision was not associated with reduction in risk of incisional site infection unless cefoxitin was used as the initial antibiotic.
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Antibacterianos , Apendicitis , Niño , Humanos , Antibacterianos/uso terapéutico , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Cefoxitina , Estudios Retrospectivos , Apendicitis/complicaciones , Resultado del Tratamiento , Apendicectomía/efectos adversosRESUMEN
Papillary thyroid carcinoma (PTC) demonstrates significantly reduced patient survival with metastatic progression. Tumor progression can be influenced by metabolism, including antioxidant glutathione (GSH). Glutathione peroxidase 4 (GPX4) is a selenoenzyme that uses GSH as a co-factor to regulate lipid peroxidation of cell membranes during increased oxidative stress. GPX4 suppression in tumor cells can induce ferroptosis. This study aims to examine ferroptosis as a potentially critical pathway in effective targeting of thyroid cancer (TC) cells. We treated human TC cells (K1, MDA-T68, MDA-T32, TPC1) with (1S,3R)-RSL3 (RSL3), a small-molecule inhibitor of GPX4 and examined the effects on ferroptosis, tumor cell survival and migration, spheroid formation, oxidative stress, DNA damage repair response, and mTOR signaling pathway in vitro. GPX4 inhibition activated ferroptosis, inducing TC cell death, rapid rise in reactive oxygen species and effectively arrested cell migration in vitro. Suppression of mTOR signaling pathway triggered autophagy. GPX4 genetic knockdown mirrored RSL3 effect on mTOR pathway suppression. RSL3 subdued DNA damage repair response by suppressing phosphorylation of nucleophosmin 1 (NPM1). Thus, observed potent induction of ferroptosis, GPX4-dependent novel suppression of mTOR pathway and DNA damage repair response in preclinical in vitro model of TC supports GPX4 targeting for therapeutic benefit in advanced therapy-resistant thyroid cancers.
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Ferroptosis , Neoplasias de la Tiroides , Humanos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Muerte Celular , Glutatión Peroxidasa/metabolismo , Glutatión/metabolismo , Neoplasias de la Tiroides/tratamiento farmacológico , Serina-Treonina Quinasas TORRESUMEN
The Necrotizing Enterocolitis Surgery Trial (NEST) highlights the importance of distinguishing necrotizing enterocolitis (NEC) from spontaneous intestinal perforation (SIP) when developing surgical treatment plans. Further research is needed to increase the accuracy of this distinction, but even with our current abilities to do this initial laparotomy appears to be optimal for infants with presumed NEC. The preferred initial operation for those with SIP is more equivocal. Rates of NEC are likely decreasing slowly, whereas those with SIP are not. New imaging modalities, especially ultrasound, are becoming more useful but require more detailed investigation. Understanding the mechanisms causing these two conditions remains of paramount importance.
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Enterocolitis Necrotizante , Enfermedades del Recién Nacido , Enfermedades del Prematuro , Perforación Intestinal , Lactante , Recién Nacido , Humanos , Enterocolitis Necrotizante/diagnóstico , Enterocolitis Necrotizante/cirugía , Perforación Intestinal/diagnóstico por imagen , Perforación Intestinal/cirugía , Recien Nacido Prematuro , Enfermedades del Prematuro/diagnóstico , Enfermedades del Prematuro/cirugíaRESUMEN
BACKGROUND & AIMS: We previously reported that colon epithelial cell silencing of Smad4 increased epithelial expression of inflammatory genes, including the chemokine c-c motif chemokine ligand 20 (CCL20), and increased susceptibility to colitis-associated cancer. Here, we examine the role of the chemokine/receptor pair CCL20/c-c motif chemokine receptor 6 (CCR6) in mediating colitis-associated colon carcinogenesis induced by SMAD4 loss. METHODS: In silico analysis of SMAD4, CCL20, and CCR6 messenger RNA expression was performed on published transcriptomic data from human ulcerative colitis (UC), and colon and rectal cancer samples. Immunohistochemistry for CCL20 and CCR6 was performed on human tissue microarrays comprising human UC-associated cancer specimens, Mice with conditional, epithelial-specific Smad4 loss with and without germline deletion of the Ccr6 gene were subjected to colitis and followed for up to 3 months. Tumors were quantified histologically, and immune cell populations were analyzed by flow cytometry and immunostaining. RESULTS: In human UC-associated cancers, loss of epithelial SMAD4 was associated with increased CCL20 expression and CCR6+ cells. SMAD4 loss in mouse colon epithelium led to enlarged gut-associated lymphoid tissues and recruitment of immune cells to the mouse colon epithelium and stroma, particularly T regulatory, Th17, and dendritic cells. Loss of CCR6 abrogated these immune responses and significantly reduced the incidence of colitis-associated tumors observed with loss of SMAD4 alone. CONCLUSIONS: Regulation of mucosal inflammation is central to SMAD4 tumor suppressor function in the colon. A key downstream node in this regulation is suppression of epithelial CCL20 signaling to CCR6 in immune cells. Loss of SMAD4 in the colon epithelium increases CCL20 expression and chemoattraction of CCR6+ immune cells, contributing to greater susceptibility to colon cancer.
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Carcinoma , Neoplasias Asociadas a Colitis , Colitis , Humanos , Ratones , Animales , Receptores CCR6/genética , Quimiocina CCL20/metabolismo , Ligandos , Inflamación , Colitis/complicaciones , ARN Mensajero , Proteína Smad4/genética , Proteína Smad4/metabolismoRESUMEN
Importance: The clinical significance of gangrenous, suppurative, or exudative (GSE) findings is poorly characterized in children with nonperforated appendicitis. Objective: To evaluate whether GSE findings in children with nonperforated appendicitis are associated with increased risk of surgical site infections and resource utilization. Design, Setting, and Participants: This multicenter cohort study used data from the Appendectomy Targeted Database of the American College of Surgeons Pediatric National Surgical Quality Improvement Program, which were augmented with operative report data obtained by supplemental medical record review. Data were obtained from 15 hospitals participating in the Eastern Pediatric Surgery Network (EPSN) research consortium. The study cohort comprised children (aged ≤18 years) with nonperforated appendicitis who underwent appendectomy from July 1, 2015, to June 30, 2020. Exposures: The presence of GSE findings was established through standardized, keyword-based audits of operative reports by EPSN surgeons. Interrater agreement for the presence or absence of GSE findings was evaluated in a random sample of 900 operative reports. Main Outcomes and Measures: The primary outcome was 30-day postoperative surgical site infections (incisional and organ space infections). Secondary outcomes included rates of hospital revisits, postoperative abdominal imaging, and postoperative length of stay. Multivariable mixed-effects regression was used to adjust measures of association for patient characteristics and clustering within hospitals. Results: Among 6133 children with nonperforated appendicitis, 867 (14.1%) had GSE findings identified from operative report review (hospital range, 4.2%-30.2%; P < .001). Reviewers agreed on presence or absence of GSE findings in 93.3% of cases (weighted κ, 0.89; 95% CI, 0.86-0.92). In multivariable analysis, GSE findings were associated with increased odds of any surgical site infection (4.3% vs 2.2%; odds ratio [OR], 1.91; 95% CI, 1.35-2.71; P < .001), organ space infection (2.8% vs 1.1%; OR, 2.18; 95% CI, 1.30-3.67; P = .003), postoperative imaging (5.8% vs 3.7%; OR, 1.70; 95% CI, 1.23-2.36; P = .002), and prolonged mean postoperative length of stay (1.6 vs 0.9 days; rate ratio, 1.43; 95% CI, 1.32-1.54; P < .001). Conclusions and Relevance: In children with nonperforated appendicitis, findings of gangrene, suppuration, or exudate are associated with increased surgical site infections and resource utilization. Further investigation is needed to establish the role and duration of postoperative antibiotics and inpatient management to optimize outcomes in this cohort of children.
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Apendicitis , Apendicectomía/efectos adversos , Apendicectomía/métodos , Apendicitis/complicaciones , Apendicitis/cirugía , Niño , Estudios de Cohortes , Gangrena/complicaciones , Humanos , Tiempo de Internación , Estudios Retrospectivos , Supuración/complicaciones , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Resultado del TratamientoRESUMEN
INTRODUCTION: Our institution has recently experienced an increase in sledding-related injuries, particularly when towed behind motorized vehicles. The purpose of this study was to characterize injury severity and clinical outcomes between pediatric patients who sustain injuries owing to motorized sledding accidents to aid in injury prevention messaging. METHODS: This retrospective study queried all patients who presented with a sledding-related injury to a single ACS-verified Level 1 Pediatric Trauma Center located in the Southeastern United States between 01/2015 and 01/2022. Demographics, injury details, and clinical outcomes were compared between two groups: patients towed behind a motorized vehicle (MOTOR) and those who were not (GRAVITY). RESULTS: Of the 67 patients included in our analysis, 15 (22%) were in the MOTOR group. Patients in the MOTOR group presented with significantly higher injury severity (ISS) and lower Glasgow coma scale (GCS) scores. Additionally, patients in this MOTOR group more often received a blood transfusion and intubation, had longer intensive care and overall hospital lengths of stay, and incurred higher hospital costs. In a multivariate analysis, the use of a motorized vehicle to sled was independently associated with increased ISS (OR: 9.7, 95% CI 1.9-17.5; p = 0.02). Two deaths occurred after sledding while being towed behind a motorized vehicle. CONCLUSION: Children experiencing sledding accidents while being towed by motorized vehicles sustain significantly more severe injuries and require more intensive treatments that together lead to increased hospital costs. These findings provide the framework for community educational initiatives and injury prevention measures to mitigate risk among children engaged in sledding. LEVEL OF EVIDENCE: IV retrospective cohort study.
Asunto(s)
Vehículos a Motor Todoterreno , Deportes de Nieve , Niño , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Estudios Retrospectivos , Centros TraumatológicosRESUMEN
This case details the presentation and surgical management of a 15-year-old male patient with multiple endocrine neoplasia syndrome type 1 (MEN1) who required distal pancreatectomy for multiple nonfunctional pancreatic tumors. An intraoperative ultrasound was utilized to allow for proper location of the distal pancreatectomy, as well as visualization of the splenic vessel relationships and to ensure all lesions were contained within the specimen. Pathology demonstrated 5 well-differentiated neuroendocrine tumors with no evidence of malignancy. This case utilized innovative technology and a multidisciplinary approach in a challenging case to achieve a safe minimally invasive resection. The use of ultrasound intraoperatively provided confidence that all lesions had been identified, as well as demonstration of safe planes separate from the nearby vasculature.