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1.
Microbiology (Reading) ; 170(1)2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38261525

RESUMO

Polymicrobial infection with Candida albicans and Staphylococcus aureus may result in a concomitant increase in virulence and resistance to antimicrobial drugs. This enhanced pathogenicity phenotype is mediated by numerous factors, including metabolic processes and direct interaction of S. aureus with C. albicans hyphae. The overall structure of biofilms is known to contribute to their recalcitrance to treatment, although the dynamics of direct interaction between species and how it contributes to pathogenicity is poorly understood. To address this, a novel time-lapse mesoscopic optical imaging method was developed to enable the formation of C. albicans/S. aureus whole dual-species biofilms to be followed. It was found that yeast-form or hyphal-form C. albicans in the biofilm founder population profoundly affects the structure of the biofilm as it matures. Different sub-populations of C. albicans and S. aureus arise within each biofilm as a result of the different C. albicans morphotypes, resulting in distinct sub-regions. These data reveal that C. albicans cell morphology is pivotal in the development of global biofilm architecture and the emergence of colony macrostructures and may temporally influence synergy in infection.


Assuntos
Candida albicans , Infecções Estafilocócicas , Hifas , Staphylococcus aureus , Imagem com Lapso de Tempo , Biofilmes
2.
J Microsc ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36692253

RESUMO

We provide a brief review of the development and application of the Mesolens and its impact on microbiology. Microbial specimens such as infected tissue samples, colonies surfaces, and biofilms are routinely collected at the mesoscale. This means that they are relatively large multimillimetre-sized samples which contain microscopic detail that must be observed to answer important questions across various sectors. The Mesolens presents the ideal imaging method to study these specimens as no other optical microscope can thanks to its unique combination of low magnification and high numerical aperture providing large field-of-view, high-resolution imaging. We demonstrate the current applications of the Mesolens to microbial imaging and go on to outline the huge potential of the Mesolens to impact other key areas of microbiology.

3.
PLoS One ; 17(10): e0273927, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36301843

RESUMO

Following mixed-methods sequential design and drawing on the message-audience congruence concept and homophily theory, across three studies in the UK, we examined the effect of gendered wording and endorser's gender on the effectiveness of leaflets promoting walking. In Study 1, a mall-intercept study achieved 247 completed questionnaires. Results demonstrated that men and women indicated the highest behavioural intentions for communal wording presented by a male endorser. However, pairwise comparisons revealed that when the wording of the advert was agentic and the endorser was male, males indicated significantly higher scores of behavioural intentions compared with females. Attitude towards the ad for women was highest for communal wording/female endorser; for men it was for agentic wording/male endorser. In Study 2, consumers' views towards the gendered content were explored in 20 semi-structured interviews. In study 3 we examined the impact of the respondent's gender role identity on gendered content effectiveness. Overall, when controlled for level of gender role identity, only masculine males evaluated leaflets featuring communal wording negatively which suggests that wording matters only for masculine males, but not for other men and women. Theoretically, we identified that gender-based message-respondent congruence is not a necessary aspect of communications to be effective, except for one group: masculine males. Our study identified dominant gender role identity as a factor that explained respondents' preferences for presented stimuli. Specifically, males who display masculine gender role identity differ in evaluations of communal wording from all other groups. Social and commercial marketers who target men and women with exercise-related services should consider the use of agentic wording endorsed by a male endorser when targeting masculine men to increase the likelihood of eliciting positive attitudes towards the communication. However, such distinctions should not be associated with differences in women's evaluations or men who do not report masculine gender role identity.


Assuntos
Atitude , Identidade de Gênero , Humanos , Masculino , Feminino , Inquéritos e Questionários , Promoção da Saúde , Reino Unido
4.
Mol Ther ; 30(10): 3270-3283, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-35619558

RESUMO

Profound natural killer (NK) cell suppression after cancer surgery is a main driver of metastases and recurrence, for which there is no clinically approved intervention available. Surgical stress is known to cause systemic postoperative changes that negatively modulate NK cell function including the expansion of surgery-induced myeloid-derived suppressor cells (Sx-MDSCs) and a marked reduction in arginine bioavailability. In this study, we determine that Sx-MDSCs regulate systemic arginine levels in the postoperative period and that restoring arginine imbalance after surgery by dietary intake alone was sufficient to significantly reduce surgery-induced metastases in our preclinical murine models. Importantly, the effects of perioperative arginine were dependent upon NK cells. Although perioperative arginine did not prevent immediate NK cell immunoparalysis after surgery, it did accelerate their return to preoperative cytotoxicity, interferon gamma secretion, and activating receptor expression. Finally, in a cohort of patients with colorectal cancer, postoperative arginine levels were shown to correlate with their Sx-MDSC levels. Therefore, this study lends further support for the use of perioperative arginine supplementation by improving NK cell recovery after surgery.


Assuntos
Arginina , Células Supressoras Mieloides , Animais , Humanos , Interferon gama/metabolismo , Células Matadoras Naturais/metabolismo , Camundongos
5.
J Pediatr Surg ; 55(12): 2752-2757, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32616413

RESUMO

BACKGROUND/RATIONALE: To describe current bowel management program (BMP) strategies in anorectal malformation (ARM) patients based on patient-level predictors using data from a multi-institutional consortium. MATERIALS/METHODS: Patient bowel function and BMP were reviewed from Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) data. The PCPLC is comprised of multidisciplinary specialists researching colorectal and pelvic disorders. Seven US institutions submitted de-identified clinical data on ARM patients into a centralized patient registry. RESULTS: The primary ARM of 624 patients was categorized into Mild (45.2%), Moderate (40.4%) or Complex (14.2%) anomaly classifications. Patient-specific BMP were examined based on age and on the presence of spinal cord/sacral anomalies. 418 (67%) enrolled patients were prescribed BMP (<5 yo 56.4%; ≥5-<12 yo 86.7%; ≥12 81.5%). Constipation was the primary chief complaint (80.2%). Forty percent of patients on a BMP were toilet trained and approximately one-half (48.5%) reported daytime stool accidents. Secondary surgical interventions for antegrade continence enemas (ACE) were examined; 14.5% of patients employed ACE strategies and utilization increased with age and varied based on anatomic anomalies. CONCLUSIONS: This is the first report on BMP strategies for patients with ARM from the Pediatric Colorectal and Pelvic Learning Consortium. Individual patient characteristics are explored for their impact on bowel management strategy utilization. LEVEL OF EVIDENCE: IV.


Assuntos
Malformações Anorretais , Incontinência Fecal , Criança , Constipação Intestinal/etiologia , Constipação Intestinal/terapia , Enema , Incontinência Fecal/etiologia , Incontinência Fecal/terapia , Humanos , Intestinos , Estudos Retrospectivos
6.
Hosp Pediatr ; 10(2): 123-128, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31900261

RESUMO

BACKGROUND: The first methodologic step needed to compare pediatric health outcomes at children's hospitals (CHs) and non-children's hospitals (NCHs) is to classify hospitals into CH and NCH categories. However, there are currently no standardized or validated methods for classifying hospitals. The purpose of this study was to describe a novel and reproducible hospital classification methodology. METHODS: By using data from the 2015 American Hospital Association survey, 4464 hospitals were classified into 4 categories (tiers A-D) on the basis of self-reported presence of pediatric services. Tier A included hospitals that only provided care to children. Tier B included hospitals that had key pediatric services, including pediatric emergency departments, PICUs, and NICUs. Tier C included hospitals that provided limited pediatric services. Tier D hospitals provided no key pediatric services. Classifications were then validated by using publicly available data on hospital membership in various pediatric programs as well as Health Care Cost Institute claims data. RESULTS: Fifty-one hospitals were classified as tier A, 228 as tier B, 1721 as tier C, and 1728 as tier D. The majority of tier A hospitals were members of the Children's Hospital Association, Children's Oncology Group, and National Surgical Quality Improvement Program-Pediatric. By using claims data, the percentage of admissions that were pediatric was highest in tier A (88.9%), followed by tiers B (10.9%), C (3.9%), and D (3.9%). CONCLUSIONS: Using American Hospital Association survey data is a feasible and valid method for classifying hospitals into CH and NCH categories by using a reproducible multitiered system.


Assuntos
Custos de Cuidados de Saúde , Hospitalização , Hospitais Pediátricos , Melhoria de Qualidade , Criança , Humanos , Unidades de Terapia Intensiva Neonatal , Unidades de Terapia Intensiva Pediátrica , Estados Unidos
7.
J Pediatr Surg ; 55(7): 1319-1323, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31109731

RESUMO

PURPOSE: To improve opioid stewardship for umbilical hernia repair in children. METHODS: An educational intervention was conducted at 9 centers with 79 surgeons. The intervention highlighted the importance of opioid stewardship, demonstrated practice variation, provided prescribing guidelines, encouraged non-opioid analgesics, and encouraged limiting doses/strength if opioids were prescribed. Three to six months of pre-intervention and 3 months of post-intervention prescribing practices for umbilical hernia repair were compared. RESULTS: A total of 343 patients were identified in the pre-intervention cohort and 346 in the post-intervention cohort. The percent of patients receiving opioids at discharge decreased from 75.8% pre-intervention to 44.6% (p < 0.001) post-intervention. After adjusting for age, sex, umbilicoplasty, and hospital site, the odds ratio for opioid prescribing in the post- versus the pre-intervention period was 0.27 (95% CI = 0.18-0.39, p < 0.001). Among patients receiving opioids, the number of doses prescribed decreased after the intervention (adjusted mean 14.3 to 10.4, p < 0.001). However, the morphine equivalents/kg/dose did not significantly decrease (adjusted mean 0.14 to 0.13, p = 0.20). There were no differences in returns to emergency departments or hospital readmissions between the pre- and post-intervention cohorts. CONCLUSIONS: Opioid stewardship can be improved after pediatric umbilical hernia repair using a low-fidelity educational intervention. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: Level II.


Assuntos
Analgésicos Opioides/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Hérnia Umbilical/cirurgia , Padrões de Prática Médica/estatística & dados numéricos , Cirurgiões/educação , Herniorrafia , Humanos , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos
8.
J Pediatr Surg ; 55(4): 702-706, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31277980

RESUMO

BACKGROUND: Adults with traumatic brain injury (TBI) who present hypertensive suffer worse outcomes and increased mortality compared to normotensive patients. The purpose of this study is to determine if age-adjusted hypertension on presentation is associated with worsened outcomes in pediatric TBI. METHODS: A retrospective chart review was conducted on pediatric patients with severe TBI admitted to a single system pediatric tertiary care center. The primary outcome was mortality. Secondary outcomes included length of stay, need for neurosurgical intervention, duration of mechanical ventilation, and the need for inpatient rehabilitation. RESULTS: Of 150 patients, 70% were hypertensive and 30% were normotensive on presentation. Comparing both groups, no statistically significant differences were noted in mortality (13.3% for both groups), need for neurosurgical intervention (51.4% vs 48.8%, p = 0.776), length of stay (6 vs 8 days, p = 0.732), duration of mechanical ventilation (2 vs 3 days, p = 0.912), or inpatient rehabilitation rates (48.6% vs 48.9%, p = 0.972). In comparing just the hypertensive patients, there was a trend toward increased mortality in the 95th and 99th percentile groups at 15.8% and 14.1%, versus the 90th percentile group at 6.7% but the difference was not statistically significant (p = 0.701). CONCLUSIONS: Contrary to the adult literature, pediatric patients with severe TBI and hypertension on presentation do not appear to have worsened outcomes compared to those who are normotensive. However, a trend toward increased mortality did exist at extremes of age adjusted hypertension. Larger scale studies are needed to validate these findings. STUDY TYPE: Retrospective cohort study LEVEL OF EVIDENCE: III.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/mortalidade , Hipertensão/complicações , Pressão Sanguínea , Lesões Encefálicas Traumáticas/reabilitação , Lesões Encefálicas Traumáticas/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Tempo de Internação , Masculino , Reabilitação Neurológica , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Respiração Artificial , Estudos Retrospectivos , Fatores de Tempo , Índices de Gravidade do Trauma
9.
J Pediatr Surg ; 54(6): 1118-1122, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30885555

RESUMO

INTRODUCTION: Biliary dyskinesia (BD) is a common indication for pediatric cholecystectomy. While diagnosis is primarily based on diminished gallbladder ejection fraction (GB-EF), work-up and management in pediatrics is controversial. METHODS: We conducted a multi-institutional retrospective review of children undergoing cholecystectomy for BD to compare perioperative work-up and outcomes. RESULTS: Six hundred seventy-eight patients across 16 institutions were included. There was no significant difference in gender, age, or BMI between institutions. Most patients were white (86.3%), non-Hispanic (79.9%), and had private insurance (55.2%). Gallbladder ejection fraction (EF) was reported in 84.5% of patients, and 44.8% had an EF <15%. 30.7% of patients were initially seen by pediatric surgeons, 31.3% by pediatric gastroenterologists, and 23.4% by the emergency department with significant variability between institutions (p < 0.001). Symptoms persisted in 35.3% of patients post-operatively with a median follow-up of 21 days (IQR 13, 34). On multivariate analysis, only non-white race and the presence of psychiatric comorbidities were associated with increased risk of post-operative symptoms. CONCLUSION: There is significant variability in evaluation and follow-up both before and after cholecystectomy for BD. Prospective research with standardized data collection and follow-up is needed to develop and validate optimal care pathways for pediatric patients with suspected BD. STUDY TYPE: Case Series, Retrospective Review. LEVEL OF EVIDENCE: Level IV.


Assuntos
Discinesia Biliar , Discinesia Biliar/epidemiologia , Discinesia Biliar/cirurgia , Criança , Colecistectomia/estatística & dados numéricos , Vesícula Biliar/cirurgia , Humanos , Estudos Retrospectivos
10.
J Pediatr Surg ; 54(6): 1104-1107, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30885561

RESUMO

BACKGROUND: A previously implemented Enhanced Recovery Protocol (ERP) for children undergoing elective gastrointestinal operations demonstrated decreased length of stay (LOS) and in-hospital opioid use. We hypothesized that the ERP would be associated with decreased postdischarge opioid prescribing. METHODS: Demographic, operative, and opioid prescription data were retrospectively compared between elective gastrointestinal surgical patients in the pre-ERP (1/2012-12/2014) and the post-ERP periods (1/2015-12/2017). RESULTS: Of the 99 patients reviewed, 56 (56.7%) were treated in the post-ERP era. Overall, 48 (48.5%) were male, and the most common operation was partial or total colectomy (n = 39, 39.4%) followed by ileocecectomy (n = 26, 26.3%). Most patients were 15-16 years of age and had inflammatory bowel disease (n = 88, 88.9%). LOS decreased from a median 4 days pre-ERP to 3 days post-ERP (p = 0.02). Patients receiving intraoperative opioids decreased from 100% to 46% (p < 0.01) and postoperative opioids from 95% to 59% (p < 0.01). Patients receiving an opioid prescription at discharge decreased from 69.8% pre-ERP to 30.9% post-ERP (p < 0.01). Among patients prescribed opioids at discharge, the number of doses (median 23 to 17, p = 0.44) and the median morphine equivalents/kg remained stable (median 2.3 to 1.7, p = 0.10). CONCLUSIONS: A pediatric gastrointestinal surgery ERP resulted in decreased postdischarge prescribing of opioids. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: Level II.


Assuntos
Analgésicos Opioides , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Prescrições de Medicamentos/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Adolescente , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Feminino , Humanos , Masculino , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos
11.
J Pediatr Surg ; 54(4): 645-650, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29970249

RESUMO

PURPOSE: The aim of this study was to determine long-term outcomes for congenital diaphragmatic hernia (CDH) patients including quality of life (QoL), symptom burden, reoperation rates, and health status. METHODS: A chart review and phone QoL survey were performed for patients who underwent CDH repair between 2007 and 2014 at a tertiary free-standing children's hospital. Comprehensive outcomes were collected including subsequent operations and health status. Associations with QoL were tested using Wilcoxon Rank-Sum tests and Pearson correlation coefficients. RESULTS: Of 102 CDH patients identified, 46 (45.1%) patient guardians agreed to participate with mean patient age of 5.8 (SD, 2.2) years at time of follow-up. Median PedsQLTM and PedsQLTM Gastrointestinal scores were 91.8 (IQR, 84.8-95.8) and 95.8 (IQR, 93.0-98.2), out of 100. Thoracoscopic repair was associated with higher PedsQLTM scores while defects with an intrathoracic stomach were associated with increased gas and bloating. No difference in QoL was found when comparing defect side, patch vs primary repair, prenatal diagnosis, extracorporeal membrane oxygenation, or recurrence. Older age weakly correlated with worse school functioning and heartburn. CONCLUSION: Children with CDH have reassuring QoL scores. Given the correlation between older age and poor school function, longer follow-up of patients with CDH may be warranted. LEVEL OF EVIDENCE: III (Retrospective comparative study).


Assuntos
Hérnias Diafragmáticas Congênitas/cirurgia , Herniorrafia/métodos , Qualidade de Vida , Criança , Pré-Escolar , Feminino , Nível de Saúde , Herniorrafia/efeitos adversos , Humanos , Lactente , Recém-Nascido , Masculino , Pais , Gravidez , Recidiva , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento
12.
J Pediatr Surg ; 54(3): 417-422, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29880397

RESUMO

PURPOSE: Neonates with intestinal atresia (IA) undergo either primary anastomosis (PA) or ostomy creation with secondary anastomosis (SA). Our purpose was to compare outcomes for PA and SA and to assess factors influencing procedure selection. METHODS: We conducted a retrospective cohort study of neonates with IA between 2009 and 2015. Patient characteristics, operative details, and outcomes were collected. Surgeon-level preferences (defined as performing >50% PA or SA) were assessed using logistic regression. RESULTS: Of 92 IA patients, 70 (76.1%) underwent PA and 22 (23.9%) underwent SA. Neonates with PA had shorter hospitalizations (27 days vs. 95 days, p < 0.001), shorter total parenteral nutrition duration (19 days vs. 74.5 days, p < 0.001), and fewer readmissions (33.3% vs. 63.2%, p = 0.024). On multivariable regression analysis, higher Apgar scores (Odds Ratio (OR) 4.16, 95% Confidence Interval (CI) 1.20-14.29) and uncomplicated atresia (OR 3.97, 95% CI 1.37-11.48) were associated with PA. At the surgeon-level, utilization of PA varied from 43.5% to 100%. Surgeon preference is not influenced by the demographic, presentation, or surgical findings of this patient population. CONCLUSIONS: PA has better outcomes than SA. Though procedural selection is influenced by the clinical status of the neonate, however surgeon preference plays a significant role in this clinical decision. LEVEL OF EVIDENCE: Level III Treatment Study.


Assuntos
Atresia Intestinal/cirurgia , Estomia/métodos , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Intestinos/cirurgia , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Estomia/efeitos adversos , Nutrição Parenteral Total/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
13.
Cancers (Basel) ; 11(1)2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30577463

RESUMO

Natural Killer (NK) cells are granular lymphocytes of the innate immune system that are able to recognize and kill tumor cells without undergoing clonal selection. Discovered over 40 years ago, they have since been recognized to possess both cytotoxic and cytokine-producing effector functions. Following trauma, NK cells are suppressed and their effector functions are impaired. This is especially important for cancer patients undergoing the removal of solid tumors, as surgery has shown to contribute to the development of metastasis and cancer recurrence postoperatively. We have recently shown that NK cells are critical mediators in the formation of metastasis after surgery. While research into the mechanism(s) responsible for NK cell dysfunction is ongoing, knowledge of these mechanisms will pave the way for perioperative therapeutics with the potential to improve cancer outcomes by reversing NK cell dysfunction. This review will discuss mechanisms of suppression in the postoperative environment, including hypercoagulability, suppressive soluble factors, the expansion of suppressive cell populations, and how this affects NK cell biology, including modulation of cell surface receptors, the potential for anergy, and immunosuppressive NK cell functions. This review will also outline potential immunotherapies to reverse postoperative NK dysfunction, with the goal of preventing surgery-induced metastasis.

14.
Pediatr Surg Int ; 34(12): 1281-1286, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30317376

RESUMO

PURPOSE: The purpose of this study was to implement a novel surgeon-reported categorization (SRC) for pediatric appendicitis severity and determine if SRC was associated with outcomes. METHODS: We conducted a retrospective review of appendectomies by 15 surgeons within a single center from January to December 2016. The SRC was defined as: simple (category 1), gangrenous or adherent (category 2A), perforation with localized abscess (category 2B), and perforation with gross contamination (category 2C). Logistic regression modeled the surgical site infections (SSI) and returns to the system. Cox proportional hazards analyses modeled the length of stay (LOS). RESULTS: The cohort included 697 patients (mean age 10.7 years). Compliance with SRC documentation increased from 33.5 to 85.9%. Review of operative findings revealed 100% concordance with SRC. The combined morbidity (SSI and revisits) rate was 9.8%. Category 2C patients had the highest odds of SSI (odds ratio 3.37 95% confidence interval 1.07-10.59). Median LOS increased with each category (category 1 = 1d, category 2A = 2d, category 2B = 4d, category 2C = 6d). When modeling intra-abdominal abscess, SRC displayed an improved model calibration and discrimination compared to wound class. CONCLUSION: SRC implementation is feasible and provides a granular assessment of appendicitis severity and outcomes. SRC may guide future quality improvement through development of grade-specific care pathways.


Assuntos
Apendicectomia/estatística & dados numéricos , Apendicite/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Cirurgiões/estatística & dados numéricos , Adolescente , Apendicite/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Tempo de Internação/tendências , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados Unidos/epidemiologia
15.
Oncoimmunology ; 7(6): e1431082, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29872554

RESUMO

Cancer surgery while necessary for primary tumor removal, has been shown to induce immune suppression and promote metastases in preclinical models and human cancer surgery patients. Activating the immune system and reversing immunosuppression have emerged as promising ways to treat cancer and they can be safely employed in the perioperative period. In this study, we evaluated the immunotherapeutic potential of phosphodiesterase-5 (PDE-5) inhibitors to target surgery-induced myeloid-derived suppressor cells (MDSC) and restore natural killer (NK) cell function in the clinically relevant perioperative period. Immunocompetent murine tumor models of major surgery were used to characterize the functional suppression of surgery-induced MDSC and to assess the in vivo efficacy of perioperative PDE5 inhibition. In cancer surgery patients with abdominal malignancies, we assessed postoperative NK cell function following co-culture with MDSC and PDE5 inhibition. Perioperative PDE5 inhibition reverses surgery-induced immunosuppression. In particular, sildenafil reduces surgery-derived granulocytic-MDSC (gMDSC) function through downregulation of arginase 1 (ARG1), IL4Ra and reactive oxygen species (ROS) expression, enabling NK cell antitumor cytotoxicity and reducing postoperative disease recurrence. By removing surgery-derived immunosuppressive mechanisms of MDSCs, sildenafil can be combined with the administration of perioperative influenza vaccination which targets NK cells to reduce postoperative metastasis. Importantly, sildenafil reverses MDSC suppression in cancer surgery patients. These findings demonstrate that PDE5 inhibitors reduce postoperative metastasis by their ability to inhibit surgery-induced MDSC. Further clinical studies are warranted to investigate the immunotherapeutic role of PDE5 inhibitors in combination with cancer surgery.

16.
Pediatr Surg Int ; 34(7): 769-774, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29728759

RESUMO

PURPOSE: Though gabapentin is increasingly used as a perioperative analgesic, data regarding effectiveness in children are limited. The purpose of this study was to evaluate gabapentin as a postoperative analgesic in children undergoing appendectomy. METHODS: A 12-month retrospective review of children undergoing appendectomy was performed at a two-hospital children's institution. Patients receiving gabapentin (GP) were matched (1:2) with patients who did not receive gabapentin (NG) based on age, sex and appendicitis severity. Outcome measures included postoperative opioid use, pain scores, and revisits/readmissions. RESULTS: We matched 29 (33.3%) GP patients with 58 (66.6%) NG patients (n = 87). The GP group required significantly less postoperative opioids than the NG group (0.034 mg morphine equivalents/kg (ME/kg) vs. 0.106 ME/kg, p < 0.01). Groups had similar lengths of time from operation to pain scores ≤ 3 (GP 12.21 vs. NG 17.01 h, p = 0.23). GP and NG had similar rates of revisit to the emergency department (13.8 vs. 10.3%, p = 0.73), readmission (6.9 vs. 1.7%, p = 0.26), and revisits secondary to surgical pain (3.4 vs. 3.4%, p = 1.00). CONCLUSION: In this single-center, retrospective cohort study, gabapentin is associated with a reduction in total postoperative opioid use in children with appendicitis. While promising, further prospective validation of clinical effectiveness is needed.


Assuntos
Aminas/administração & dosagem , Analgésicos não Narcóticos/administração & dosagem , Apendicectomia , Apendicite/cirurgia , Ácidos Cicloexanocarboxílicos/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Ácido gama-Aminobutírico/administração & dosagem , Adolescente , Criança , Feminino , Gabapentina , Humanos , Masculino , Estudos Retrospectivos
17.
J Surg Res ; 224: 79-88, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29506856

RESUMO

BACKGROUND: Our goal is to determine short- and long-term outcomes of simple gastroschisis (SG) and complicated gastroschisis (CG) patients including quality of life (QoL) measures, surgical reoperation rates, and residual gastrointestinal symptom burden. MATERIALS AND METHODS: Retrospective chart review of patients who underwent surgical repair of gastroschisis between January 1, 2009, and December 31, 2012, was performed at a quaternary children's hospital. Parent telephone surveys were conducted to collect information on subsequent operations and current health status as well as to assess QoL using two validated tools. RESULTS: Of 143 patients identified, 45 (31.5%) were reached and agreed to participate with a median follow-up age of 4.7 y. Although CG was associated with short-term outcomes such as longer length of stay, longer days to feeds, and higher complication rates, there were no major differences in long-term QoL outcomes when comparing SG and CG. Children with CG experienced abdominal pain/gas/diarrhea more often than those with SG and required more major abdominal procedures than those with SG (15% versus 0%, P = 0.009). CONCLUSIONS: Despite worse short-term outcomes, presence of certain gastrointestinal symptoms, and need for more surgical interventions for patients with CG, and overall QoL scores were reassuringly similar to those with SG.


Assuntos
Gastrosquise/cirurgia , Criança , Pré-Escolar , Família , Feminino , Gastrosquise/complicações , Gastrosquise/psicologia , Humanos , Tempo de Internação , Masculino , Qualidade de Vida , Estudos Retrospectivos
18.
JAMA Surg ; 153(6): 544-550, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29387882

RESUMO

Importance: The pediatric perforated appendix rate is a quality metric measured by the Agency for Healthcare Research and Quality (AHRQ) that reflects access to care. The association of health care utilization prior to presentation with appendicitis is unknown. Objective: To determine whether increased health care utilization prior to presentation with appendicitis is associated with lower perforated appendicitis rates in children. Design, Setting, and Participants: Retrospective cohort study of privately insured children drawn from large employer and insurance company administrative data found in the Truven MarketScan national insurance claims database. Cases of appendicitis were identified among 38 348 children 18 years or younger from January 1, 2010, through December 31, 2013, with corresponding primary health care encounters from January 1, 2009, through December 31, 2012. In all, 19 109 eligible children were identified using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes for appendicitis after excluding those patients who did not have continuous insurance coverage during the study period. Statistical analysis was performed from September 1, 2016, to October 15, 2017. Exposures: Health care utilization was determined by the number of outpatient clinic encounters for each patient in the 1 to 12 months before presentation with appendicitis. Main Outcomes and Measures: Perforated appendicitis was defined according to the AHRQ by using ICD-9 codes for perforation and hospital length of stay of 3 or more days. Logistic regression models were used for perforated appendicitis after adjustment for age, sex, income, gastrointestinal comorbidities, geographic region, and insurance type. Results: We identified 38 348 children 18 years or younger with ICD-9 diagnosis codes for appendicitis, and 19 109 children remained for analysis after applying exclusion criteria. Of these, 11 422 were boys (59.8%); the mean (SD) age was 12.4 (3.9) years. Of the 19 109 children identified who underwent appendectomy, 5509 (28.8%) presented with perforated appendicitis. Children with perforation had lower outpatient health care utilization in the year before presentation compared with those diagnosed with acute appendicitis (4554 of 5509 children [82.7%] vs 11 937 of 13 600 [87.8%]; P < .001). In the adjusted model, outpatient health care utilization before presentation was associated with lower odds of perforated appendicitis (odds ratio [OR], 0.63; 95% CI, 0.58-0.69; P < .001). This association increased with visit frequency in the year before presentation (OR, 0.86; 95% CI, 0.77-0.95 for 1-2 visits, P = .003; OR, 0.61; 95% CI, 0.55-0.67 for 3-6 visits, P < .001; and OR, 0.43; 95% CI, 0.38-0.48 for ≥7 visits [5-18 years], P < .001). Covariates associated with perforation included younger age, geographic region, family income, and higher out-of-pocket insurance plans. Conclusions and Relevance: Among insured children 18 years or younger, increased health care utilization was associated with lower rates of perforated appendicitis. Primary health care relationships may facilitate timely presentation or serve as a marker for health-related self-efficacy, thereby contributing to outcomes for acute surgical conditions.


Assuntos
Apendicite/epidemiologia , Seguro Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Doença Aguda , Adolescente , Apendicectomia/estatística & dados numéricos , Apendicite/economia , Apendicite/cirurgia , Criança , Feminino , Seguimentos , Humanos , Incidência , Masculino , Estudos Retrospectivos , Estados Unidos/epidemiologia
19.
J Pediatr Surg ; 53(9): 1655-1659, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29429770

RESUMO

BACKGROUND: Long-term dysphagia occurs in up to 50% of repaired esophageal atresia and tracheoesophageal fistula (EA/TEF) patients. The underlying factors are unclear and may include stricture, esophageal dysmotility, or associated anomalies. Our purpose was to determine whether structural airway abnormalities (SAA) are associated with dysphagia in EA/TEF. METHODS: We conducted a retrospective chart review of children who underwent EA/TEF repair in our hospital system from 2007 to 2016. Children with identified SAA (oropharyngeal abnormalities, laryngeal clefts, laryngomalacia, vocal cord paralysis, and tracheomalacia) were compared to those without airway abnormalities. Dysphagia outcomes were determined by the need for tube feeding and the modified pediatric Functional Oral Intake Scale (FOIS) at 1 year. RESULTS: SAA was diagnosed in 55/145 (37.9%) patients with EA/TEF. Oropharyngeal aspiration was more common in children with SAA (58.3% vs. 36.4%, p=0.028). Children with SAA were more likely to require tube feeding both at discharge (79.6% vs. 48.3%, p<0.001) and at 1 year (52.7% vs. 13.6%, p<0.001) and had lower mean FOIS (4.18 vs. 6.21, p<0.001). In the logistic regression model adjusting for gestational age, long gap EA, and esophageal stricture, the presence of SAA remained a significant risk factor for dysphagia (OR 4.17 (95% CI 1.58-11.03)). CONCLUSION: SAA are common in children with EA/TEF and are associated with dysphagia, even after accounting for gestational age, esophageal gap and stricture. This study highlights the need for a multidisciplinary approach, including early laryngoscopy and bronchoscopy, in the evaluation of the EA/TEF child with dysphagia. LEVEL OF EVIDENCE: Level II retrospective prognostic study.


Assuntos
Anormalidades Múltiplas , Transtornos de Deglutição/etiologia , Atresia Esofágica/complicações , Anormalidades do Sistema Respiratório/complicações , Fístula Traqueoesofágica/complicações , Anormalidades Múltiplas/cirurgia , Criança , Pré-Escolar , Transtornos de Deglutição/diagnóstico , Atresia Esofágica/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Prognóstico , Anormalidades do Sistema Respiratório/cirurgia , Estudos Retrospectivos , Fatores de Risco , Fístula Traqueoesofágica/cirurgia
20.
J Am Coll Surg ; 226(5): 917-924.e1, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29458092

RESUMO

BACKGROUND: The American College of Surgeons in 2015 instituted the Children's Surgery Verification program delineating requirements for hospitals providing pediatric surgical care. Our purpose was to examine possible effects of the Children's Surgery Verification program by evaluating neonates undergoing high-risk operations. STUDY DESIGN: Using the Kid's Inpatient Database 2009, we identified infants undergoing operations for 5 high-risk neonatal conditions. We considered all children's hospitals and children's units Level I centers and considered all others Level II/III. We estimated the number of neonates requiring relocation and the additional distance traveled. We used propensity score adjusted logistic regression to model mortality at Level I vs Level II/III hospitals. RESULTS: Overall, 7,938 neonates were identified across 21 states at 91 Level I and 459 Level II/III hospitals. Based on our classifications, 2,744 (34.6%) patients would need to relocate to Level I centers. The median additional distance traveled was 6.6 miles. The maximum distance traveled varied by state, from <55 miles (New Jersey and Rhode Island) to >200 miles (Montana, Oregon, Colorado, and California). The adjusted odds of mortality at Level II/III vs Level I centers was 1.67 (95% CI 1.44 to 1.93). We estimate 1 life would be saved for every 32 neonates moved. CONCLUSIONS: Although this conservative estimate demonstrates that more than one-third of complex surgical neonates in 2009 would have needed to relocate under the Children's Surgery Verification program, the additional distance traveled is relatively short for most but not all, and this program might improve mortality. Local level ramifications of this novel national program require additional investigation.


Assuntos
Hospitais Pediátricos/normas , Doenças do Recém-Nascido/cirurgia , Procedimentos Cirúrgicos Operatórios/normas , Feminino , Mortalidade Hospitalar , Humanos , Recém-Nascido , Doenças do Recém-Nascido/mortalidade , Masculino , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios/mortalidade , Viagem , Estados Unidos
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