ABSTRACT
This review focuses on the crucial role of the intestinal epithelium in maintaining intestinal homeostasis and its significance in the pathogenesis of necrotizing enterocolitis (NEC) and inflammatory bowel diseases (IBD). NEC is a devastating neonatal disease, while IBD represents a global healthcare problem with increasing incidence. The breakdown of the intestinal barrier in neonates is considered pivotal in the development and progression of both disorders. This review provides an overview of the current state of in vitro, ex vivo, and animal models to study epithelial injury in NEC and IBD, addressing pertinent questions that engage clinicians and researchers alike. Despite significant advancements in early recognition and aggressive treatment, no single therapy has been conclusively proven effective in reducing the severity of these disorders. Although early interventions have improved clinical outcomes, NEC and IBD continue to impose substantial morbidity, mortality, and economic burdens on affected individuals and society. Consequently, exploring alternative therapeutic options capable of preventing and treating the sequelae of NEC and IBD has become a pressing necessity. In recent decades, extracellular vehicles (EVs) have emerged as a potential solution to modulate the pathogenic mechanism in these multifactorial and complex disorders. Despite the diverse array of proposed models, a comprehensive model to investigate and decelerate the progression of NEC and IBD remains to be established. To bridge the translational gap between preclinical studies and clinical applications, enhancements in the technical development of gut-on-a-chip models and EVs hold considerable promise.
Subject(s)
Enterocolitis, Necrotizing , Extracellular Vesicles , Infant, Newborn, Diseases , Inflammatory Bowel Diseases , Animals , Infant, Newborn , Humans , Enterocolitis, Necrotizing/diagnosis , Enterocolitis, Necrotizing/therapy , Enterocolitis, Necrotizing/metabolism , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Disease Models, Animal , Extracellular Vesicles/metabolismABSTRACT
PURPOSE: To investigate the impact of after-hours surgery on the outcomes of pediatric kidney transplantation (KT). METHODS: Medical records of pediatric KTs performed at a single institution between 2013 and 2021 were retrospectively reviewed. The population was split into three groups according to the incision time and calendar: ordinary day (8.00 AM - 6.30 PM), day-off, and night-time (6.30 PM - 8.00 AM). The following endpoints were compared: ischemia times, length of surgery, complications, delayed graft function (DGF), primary graft non-function (PGNF), and eGFR at three-month follow-up. RESULTS: Ninety-six non-living donor KTs were performed, median age 11 (IQR 4.3-14) years and median body weight 26 (IQR 13-50) kg. Forty-one (43%) were performed during night-time and 28 (29%) during day-off. Ischemia times were similar (p = 0.769, p = 0.536). Day-off KTs presented an extended length of surgery (p = 0.011). Thirty-two complications were reported in 31 KTs. No difference in the overall rate of complications, DGF, PNGF, and three-month eGFR was found (p = 0.669, p = 0.383, p = 0.949, p = 0.093). Post-operative bleedings were more common in days-off (p = 0.003). CONCLUSION: The number of pediatric KTs performed during after-hours was considerable. Even though similar outcomes were reported, more caution should be focused on the KTs performed in days-off to avoid severe complications.
Subject(s)
Kidney Transplantation , Humans , Child , Retrospective Studies , Graft Survival , Cadaver , Ischemia , Risk Factors , KidneyABSTRACT
INTRODUCTION: Over the years, congenital lung malformations (CLM) management remains a controversial topic in pediatric thoracic surgery. The Italian Society of Pediatric Surgery performed a national survey to study the current management variability among centers, trying to define national guidelines and a standardized approach of children with congenital lung malformations. METHODS: Following a National Society approval, an electronic survey including 35 items on post-natal management was designed, focusing on surgical, anesthesiology, radiology and pneumology aspects. The survey was conducted contacting all pediatric surgical units performing thoracic surgery. RESULTS: 39 pediatric surgery units (97.5%) participated in the study. 13 centers (33.3%) were classified as high-volume (Group A), while 26 centers (66.7%) were low volume (Group B). Variances in diagnostic imaging protocols were observed, with Group A performing fewer CT scans compared to Group B (p = 0.012). Surgical indications favored operative approaches for asymptomatic CLM and pulmonary sequestrations in both groups, while a wait-and-see approach was common for congenital lobar emphysema. Surgical timing for asymptomatic CLM differed significantly, with most high-volume centers operating on patients younger than 12 months (p = 0.02). Thoracoscopy was the preferred approach for asymptomatic CLM in most of centers, while postoperative long-term follow-up was not performed in most of the centers. CONCLUSION: Thoracoscopic approach seems uniform in asymptomatic CLM patients and variable in symptomatic children. Lack of uniformity in surgical timing and preoperative imaging assessment has been identified as key areas to establish a common national pattern of care for CLM.
Subject(s)
Lung Diseases , Respiratory System Abnormalities , Humans , Child , Lung Diseases/congenital , Respiratory System Abnormalities/surgery , Pneumonectomy/methods , Lung/diagnostic imaging , Lung/surgery , Lung/abnormalities , Italy , Retrospective StudiesABSTRACT
PURPOSE: Accurate histological diagnosis in Hirschsprung disease (HD) is challenging, due to its complexity and potential for errors. In this study, we present an artificial intelligence (AI)-based method designed to identify ganglionic cells and hypertrophic nerves in HD histology. METHODS: Formalin-fixed samples were used and an expert pathologist and a surgeon annotated these slides on a web-based platform, identifying ganglionic cells and nerves. Images were partitioned into square sections, augmented through data manipulation techniques and used to develop two distinct U-net models: one for detecting ganglionic cells and normal nerves; the other to recognise hypertrophic nerves. RESULTS: The study included 108 annotated samples, resulting in 19,600 images after data augmentation and manually segmentation. Subsequently, 17,655 slides without target elements were excluded. The algorithm was trained using 1945 slides (930 for model 1 and 1015 for model 2) with 1556 slides used for training the supervised network and 389 for validation. The accuracy of model 1 was found to be 92.32%, while model 2 achieved an accuracy of 91.5%. CONCLUSION: The AI-based U-net technique demonstrates robustness in detecting ganglion cells and nerves in HD. The deep learning approach has the potential to standardise and streamline HD diagnosis, benefiting patients and aiding in training of pathologists.
Subject(s)
Deep Learning , Hirschsprung Disease , Humans , Hirschsprung Disease/diagnosis , Hirschsprung Disease/surgery , Artificial Intelligence , Hypertrophy , NeuronsABSTRACT
BACKGROUND: Postoperative hypocalcemia is a frequent complication after thyroidectomy. Hypoparathyroidism may develop as transient (TtHP), with normalization within six months from surgery, or permanent (PtHP) if the patient requires replacement therapy. We analyzed factors associated with the development of postoperative hypoparathyroidism and in detail PtHP following thyroid surgery in a pediatric population. PROCEDURE: A retrospective multicenter study analyzing 326 patients was carried out. We recorded gender, age, tumor size, thyroiditis, extrathyroidal extension, lymph node dissection (central/lateral compartment, unilateral/bilateral), parathyroid autotransplantation, and histology. Additionally, calcium levels were acquired postoperatively. RESULTS: We analyzed pediatric patients ≤18 years who underwent thyroidectomy clustered into age groups (≤15 or > 15). Patients' mean follow-up was 5.8 years (1-11 years). Postoperative hypoparathyroidism occurred in 36 (11.0%): 20 cases (6.13%) developed PtHP. Postoperative hypoparathyroidism was more frequent in younger patients (P = 0.014), in larger tumors (P < 0.001), in case of extrathyroidal extension (P = 0.037), and in central compartment (P = 0.020) and bilateral lymph node dissection (P = 0.030). PtHP was more frequent in older patients (P = 0.014), in case of thyroiditis (P < 0.001), and extrathyroidal extension (P < 0.001). Concerning the first postoperative calcium level measurement, in the postoperative hypoparathyroidism group, we registered a 8.17 mg/dL value with 14% pre/postoperative decrease (ΔCa ), whereas in PtHP patient group calcium level was 7.91 mg/dL with 16.7% ΔCa . CONCLUSIONS: The risk of postoperative hypoparathyroidism is related to younger age, tumor size, central compartment and bilateral lymph node dissection, extrathyroidal extension, and decrease in postoperative calcium levels. The risk of PtHP is related to older age, thyroiditis, extrathyroidal extension, and decrease in postoperative calcium levels.
Subject(s)
Hypocalcemia , Hypoparathyroidism , Thyroid Neoplasms , Aged , Calcium , Child , Humans , Hypocalcemia/epidemiology , Hypocalcemia/etiology , Hypoparathyroidism/epidemiology , Hypoparathyroidism/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Thyroid Neoplasms/pathology , Thyroidectomy/adverse effectsABSTRACT
BACKGROUND: A prompt detection of graft venous thrombosis might preserve the transplanted organ. A real-time near-infrared spectroscopy (NIRS) monitoring of the allograft perfusion could fulfill this goal. The aim of this work was to report the trend of allograft perfusion (rSO2) after pediatric kidney transplantation (KT) complicated by graft venous thrombosis. CASE PRESENTATION: An infant, affected by end-stage kidney disease due to posterior urethral valves, underwent non-living donor KT. The allograft presented both arterial and venous variants and required a complex bench surgery reconstruction. The perfusion of the allograft was monitored by real-time transcutaneous NIRS. The early post-operative was conditioned by worsening clinical conditions, and a graft venous thrombosis was detected after four hours since the transplantation. NIRS monitoring lasted for 348 minutes. Median lower pole rSO2-value was 65% (IQR 62-66%), while the median upper pole rSO2-value was 70% (IQR 70-71%). These data reflected the congestion of the lower pole, observed at the end of the transplantation. The lower pole showed inferior rSO2 values (p<0.0001). At the end of the monitoring, the decrease in peripheral rSO2, measured in left lower limb as a benchmark, was consistent with the ongoing hypovolemic shock and severe acute anemia. CONCLUSION: Transcutaneous NIRS might be a reliable device for monitoring allograft and peripheric perfusion after pediatric KT. The modifications of rSO2 values helped the clinicians manage the patients in the post-operative and early detect acute complications.
Subject(s)
Kidney Transplantation , Venous Thrombosis , Child , Humans , Infant , Kidney , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Monitoring, Physiologic/methods , Oxygen , Spectroscopy, Near-Infrared/methods , Venous Thrombosis/diagnosis , Venous Thrombosis/etiologyABSTRACT
BACKGROUND: Pediatric robotic-assisted surgeries have increased in recent years; however, guidance documents are still lacking. This study aimed to develop evidence-based recommendations, or best practice statements when evidence is lacking or inadequate, to assist surgical teams internationally. METHODS: A joint consensus taskforce of anesthesiologists and surgeons from the Italian Society of Pediatric and Neonatal Anesthesia and Intensive Care (SARNePI) and the Italian Society of Pediatric Surgery (SICP) have identified critical areas and reviewed the available evidence. The taskforce comprised 21 experts representing the fields of anesthesia (n = 11) and surgery (n = 10) from clinical centers performing pediatric robotic surgery in the Italian cities of Ancona, Bologna, Milan, Naples, Padua, Pavia, Perugia, Rome, Siena, and Verona. Between December 2020 and September 2021, three meetings, two Delphi rounds, and a final consensus conference took place. RESULTS: During the first planning meeting, the panel agreed on the specific objectives, the definitions to apply, and precise methodology. The project was structured into three subtopics: (i) preoperative patient assessment and preparation; (ii) intraoperative management (surgical and anesthesiologic); and (iii) postoperative procedures. Within these phases, the panel agreed to address a total of 18 relevant areas, which spanned preoperative patient assessment and patient selection, anesthesiology, critical care medicine, respiratory care, prevention of postoperative nausea and vomiting, and pain management. CONCLUSION: Collaboration among surgeons and anesthesiologists will be increasingly important for achieving safe and effective RAS procedures. These recommendations will provide a review for those who already have relevant experience and should be particularly useful for those starting a new program.
Subject(s)
Anesthesia , Anesthesiology , Robotic Surgical Procedures , Infant, Newborn , Child , Humans , Consensus , Critical CareABSTRACT
Pediatric adrenocortical tumors (ACT) are rare and sometimes aggressive malignancies, but there is no consensus on the outcome predictors in children. A systematic search of MEDLINE, SCOPUS, Web of Science, and the Cochrane Library for studies from 1994 to 2020 about pediatric ACT was performed. In 42 studies, 1006 patients, aged 0-18 years, were included. The meta-analyses resulted in the following predictors of better outcome: age <4 years (P < .00001), nonsecreting tumors (P = .004), complete surgical resection (P < .00001), tumor volume (P < .0001), tumor weight (P < .00001), tumor maximum diameter (P = .0009), and Stage I disease (P < .00001). Moreover, patients affected by Cushing syndrome showed a worse outcome (P < .0001). International prospective studies should be implemented to standardize clinical prognostic factors evaluation, together with pathological scores, in the stratification of pediatric ACT.
Subject(s)
Adrenal Cortex Neoplasms/mortality , Adrenocortical Carcinoma/mortality , Adrenal Cortex Neoplasms/pathology , Adrenal Cortex Neoplasms/therapy , Adrenocortical Carcinoma/pathology , Adrenocortical Carcinoma/therapy , Child , Humans , Prognosis , Survival RateABSTRACT
Extraperitoneal approach is sometimes recommended for kidney transplantation (KT) in children weighting <15 kg. We hypothesized that this approach might be as successful as in patients with normal weight. Data of all consecutive KTs performed between 2013 and 2019 were retrospectively reviewed. Early outcomes and surgical complications were compared between children weighing ≤15 kg (low-weight (LW) group) and those weighing >15 kg (Normal-weight (NW) group). All the 108 KTs were performed through an extraperitoneal approach. The LW group included 31 patients (mean age 3.5 ± 1.4 years), whose mean weight was 11.1 ± 2.0 kg. In the LW group,-a primary graft nonfunction (PNGF) occurred in one patient (3.2%), surgical complications occurred in nine (29%), with four venous thrombosis. In the NW group, PNGF occurred in one case (1.3%), delayed graft function (DGF) in eight (10%), surgical complications in 11 (14%) with only one case of venous thrombosis. In both groups, no need for patch during wound closure and no wound dehiscence were reported. The extraperitoneal approach can be effectively used in LW children. No differences were observed in the overall complication rate (P = 0.10), except for the occurrence of venous thrombosis (P = 0.02). This might be related to patients' characteristics of the LW group.
Subject(s)
Kidney Transplantation , Child , Child, Preschool , Graft Survival , Humans , Kidney Transplantation/adverse effects , Postoperative Complications/epidemiology , Retrospective StudiesABSTRACT
BACKGROUND: Allograft venous thrombosis is a severe complication after kidney transplantation (KT). Early diagnosis and prompt treatment are crucial in preserving the survival of the allograft. In this study, we aimed to describe an emergent strategy for the management of acute allograft venous thrombosis. CASE PRESENTATION: A 4-year-old girl, weighing 13.5 kg, was diagnosed with bilateral congenital renal hypodysplasia, urogenital sinus and anorectal malformation. The patient was referred to our department for living-donor KT. Her mother was eligible as a donor, presenting a body weight ratio of 1:4.5. Thrombosis of the inferior vena cava (ICV) was also identified, without any predisposing factor for thrombophilia. KT was performed by an extraperitoneal approach without complications. Venous anastomosis required a human vascular graft sutured to the ICV, and renal artery was anastomosed to the aorta. On postoperative day (POD) 8, acute abdominal pain and hematuria led to the diagnosis of an allograft venous thrombosis. An emergent laparotomy was required to explant the allograft, followed by bench surgery. The allograft was irrigated with thrombolytic agents and lactated Ringer's solution and then after removing the venous vascular graft, it was reimplanted through vascular anastomosis with the ICV and aorta. The recovery of perfusion and function was good with diuresis since day 4 after re-surgery. At 2-year follow-up, the child presented normal allograft function with an estimated GFR of 65 ml/min/1.73 m2 . CONCLUSION: According to our experience, explantation of the kidney allograft, followed by irrigation with thrombolytics in bench surgery, and reimplantation resulted in unexpected optimal outcomes in the case of allograft venous thrombosis.
Subject(s)
Kidney Transplantation , Postoperative Complications/therapy , Thrombolytic Therapy/methods , Venous Thrombosis/therapy , Anastomosis, Surgical , Child, Preschool , Combined Modality Therapy , Female , Humans , Living Donors , Reoperation , Vascular Grafting , Vena Cava, Inferior/surgeryABSTRACT
The diagnosis of balanitis xerotica obliterans (BXO) in children may be challenging, since clinical examination only could lead to an underestimation of its incidence. The aim of this retrospective and single-centre study is to assess the diagnostic performance of clinical examination, together with clinical history, in identifying BXO. Ninety-seven children underwent circumcision for phimosis from 2015 to 2019. Histology was routinely performed. Cohen's kappa coefficient, sensitivity, specificity, predictive values, likelihood ratios and accuracy of macroscopic appearance of the foreskin, steroid administration and past medical history were estimated. Forty-eight patients (50%) were affected by BXO; 31 of them (69%) presented with suggestive clinical signs. A strictured or whitish urethral meatus was detected during surgery in nine cases (19%); this was associated to allergic or immune diseases (p = 0.046). Foreskin appearance alone mildly correlated with histology (k = 0.494; p < 0.001) and it showed a diagnostic accuracy of 75%. The specificity and positive predictive value of abnormal macroscopic findings at examination, together with a positive clinical history for other allergic or immune diseases, and/or for balanitis, were 100% and the positive likelihood ratio was greater than 10. Conversely, sensitivity decreased to 4.5% (95% CI 0-11%).Conclusion: Foreskin appearance together with clinical history could predict BXO with certainty. However, since the absence of a positive medical history could not exclude the diagnosis, foreskin histology is still highly recommended. What is Known: ⢠Occurrence of balanitis xerotica obliterans may be underestimated in children and it could lead to long-term complications. ⢠The diagnostic accuracy of clinical examination is controversial. What is New: ⢠Clinical signs together with patients' medical history present high specificity and positive predictive values but low sensitivity. ⢠When suggestive clinical aspects are present, patient should be referred to surgery avoiding prolonged conservative treatment; and preputial histology is highly recommended.
Subject(s)
Balanitis Xerotica Obliterans , Lichen Sclerosus et Atrophicus , Phimosis , Balanitis Xerotica Obliterans/diagnosis , Child , Foreskin , Humans , Male , Phimosis/diagnosis , Retrospective StudiesABSTRACT
BACKGROUND: The use of transcutaneous near-infrared spectroscopy (NIRS) for monitoring the perfusion of kidney and liver allografts has been proposed in the last years. This device might detect an early decrease in allograft oxygenation allowing prompt detection of vascular complications. METHODS: A systematic review of the literature about the use of transcutaneous NIRS in monitoring allograft perfusion was performed according to the PRISMA guidelines. RESULTS: The authors screened 1313 papers. The search yielded five pertinent articles. Three of them reported the experience of NIRS in kidney transplantation and the other two dealt with its use in liver transplantation, for a total of 55 paediatric patients and 121 adults. In the studies concerning kidney transplantation, NIRS measurements were significantly related to serum creatinine, estimated glomerular filtration rate (eGFR), urinary neutrophil gelatinase-associated lipocalin (u-NGAL), serum lactate, resistive index assessed by Doppler-ultrasonography and systolic blood pressure. The two studies dealing with liver transplantation found a significant decrease in liver regional oxygenation, assessed by NIRS, before the occurrence of vascular complications. CONCLUSIONS: Preliminary studies have related NIRS monitoring to kidney and liver allograft perfusion, both in adults and children. Further investigation is needed to establish the normal range of NIRS values and the factors influencing NIRS monitoring.
Subject(s)
Kidney , Spectroscopy, Near-Infrared , Adult , Allografts , Child , Humans , Kidney/diagnostic imaging , Liver/diagnostic imaging , PerfusionABSTRACT
PURPOSE: Women with anorectal malformation (ARM) are expected to have a normal life span, therefore, gynecological and psycho-sexual issues are also important. Aim of the study was to assess these aspects in adult females with history of ARM. METHODS: Thirty-seven women from two ARM referral centers, aged ≥ 16, were identified. Gynecologic visit, cervicovaginal swab, pelvic ultrasound, FSH, LH, prolactin, progesterone, 17-ß-estradiol, DHEAS, testosterone, TSH during follicular and luteal phases, and administration of FSFI questionnaire to screen the female sexual functioning were performed. Data were compared with six controls. RESULTS: Nineteen patients, mean age 21.7 (16-45), participated to the study. Associated anomalies, mostly affecting limbs, vertebrae and genitalia, were present in 57.8% of cases. Mullerian anomalies were retrieved in 36.8%. Hormones' levels were normal. Concerning sexual functioning, four women (21%) reported dyspareunia or impossible penetration, four did not answer the FSFI questionnaire due to lack of confidence about their sexuality, and three scored lower than the cut-off value for female sexual function. CONCLUSION: This study confirms the importance of a multidisciplinary long-term follow-up for ARM patients, including a careful study of the reproductive tract to detect and treat those conditions that could affect the fertility. Moreover, an appropriate psychological support should be provided.
Subject(s)
Anorectal Malformations/psychology , Adolescent , Adult , Aged , Anorectal Malformations/therapy , Case-Control Studies , Female , Humans , Quality of Life , Sexual Behavior/psychology , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Congenital pouch colon (CPC) is a rare variant of anorectal malformations (ARM) with its highest reported incidence in India. We aimed to describe five patients affected by CPC, in which the tissue from the terminal dilated colon has been successfully used and to discuss our results on the light of an extended revision of the literature. MATERIALS AND METHODS: The clinical details of five cases treated for CPC in two Italian Centers were retrospectively reviewed assessing the fate of the terminal dilated colon. RESULTS: In all cases, the tissue from dilated colon has been used. The double vascular system of the dilated pouch allowed increasing bladder capacity (case 4), reconstruction of the vagina (case 3, 5), and lengthening of the colon (case 1, 2, 5).In our series, 3/5 have a good bowel control with daily bowel management after ARM correction. In literature, there are not differences in terms of dependence from bowel management in patients with pouch resected and in patients with pouch saved (P = 0.16). CONCLUSIONS: We acknowledge that the analysis of the available literature is limited by the absence of studies with high level of evidence and the removal or the preservation of the abnormal colon tissue seems to follow the surgeon preferences.
ABSTRACT
PURPOSE: Necrotizing enterocolitis (NEC) is a severe neonatal disease. The present study aimed to identify factors predisposing the development of severe forms of NEC. METHODS: This retrospective study examined NEC patients in a single centre between 2002 and 2015. Data concerning clinical characteristics, therapeutic management as well as short-term outcomes were collected. We compared the patients receiving successful medical treatment and those requiring surgical intervention. Patients who underwent surgery were distinguished in three subcategories. Bivariate and multivariate analyses were used for the statistical analysis. RESULTS: We identified 155 patients in the study period. 102 were treated conservatively and 53 required surgery. 8 received a primary peritoneal drainage, 31 received a drainage and a subsequent laparotomy and 14 received a laparotomy. Multivariate regression analysis identified a lower risk for surgery with a later onset and higher serum pH values, whereas an increased risk with higher C reactive Protein (CRP) levels at the onset. Pneumatosis intestinalis was identified as a protective factor. Overall mortality was 6.4%, with higher percentage in surgical NEC. CONCLUSION: This study suggests that a later onset is a protective sign for the progression to surgery, whereas lower pH values and higher CRP levels are prognostic factors associated with the need for surgery. The line of treatment involving explorative laparotomy in case of perforation seems to be rewarded by low morbidity and mortality rate.
Subject(s)
Enterocolitis, Necrotizing/surgery , Severity of Illness Index , Age of Onset , Blood Chemical Analysis , C-Reactive Protein/analysis , Conservative Treatment/statistics & numerical data , Drainage/statistics & numerical data , Female , Humans , Hydrogen-Ion Concentration , Infant, Newborn , Laparotomy/statistics & numerical data , Male , Multivariate Analysis , Retrospective Studies , Risk AssessmentABSTRACT
Skeletal muscle tissue engineering (TE) aims to efficiently repair large congenital and acquired defects. Biological acellular scaffolds are considered a good tool for TE, as decellularization allows structural preservation of tissue extracellular matrix (ECM) and conservation of its unique cytokine reservoir and the ability to support angiogenesis, cell viability, and proliferation. This represents a major advantage compared to synthetic scaffolds, which can acquire these features only after modification and show limited biocompatibility. In this work, we describe the ability of a skeletal muscle acellular scaffold to promote vascularization both ex vivo and in vivo. Specifically, chicken chorioallantoic membrane assay and protein array confirmed the presence of pro-angiogenic molecules in the decellularized tissue such as HGF, VEGF, and SDF-1α. The acellular muscle was implanted in BL6/J mice both subcutaneously and ortotopically. In the first condition, the ECM-derived scaffold appeared vascularized 7 days post-implantation. When the decellularized diaphragm was ortotopically applied, newly formed blood vessels containing CD31âº, αSMAâº, and vWF⺠cells were visible inside the scaffold. Systemic injection of Evans Blue proved function and perfusion of the new vessels, underlying a tissue-regenerative activation. On the contrary, the implantation of a synthetic matrix made of polytetrafluoroethylene used as control was only surrounded by vWF⺠cells, with no cell migration inside the scaffold and clear foreign body reaction (giant cells were visible). The molecular profile and the analysis of macrophages confirmed the tendency of the synthetic scaffold to enhance inflammation instead of regeneration. In conclusion, we identified the angiogenic potential of a skeletal muscle-derived acellular scaffold and the pro-regenerative environment activated in vivo, showing clear evidence that the decellularized diaphragm is a suitable candidate for skeletal muscle tissue engineering and regeneration.
Subject(s)
Diaphragm/chemistry , Extracellular Space/chemistry , Neovascularization, Physiologic , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Animals , Cells, Cultured , Chemokine CXCL12/analysis , Chemokine CXCL12/pharmacology , Chick Embryo , Diaphragm/cytology , Female , Hepatocyte Growth Factor/analysis , Hepatocyte Growth Factor/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Male , Mice , Mice, Inbred C57BL , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor A/pharmacologyABSTRACT
BACKGROUND: Minimal access adrenal surgery (MAAS) for adrenal pathologies is the standard for many pediatric surgical centers. However, the literature offers few reports and minimal evidence from small case series. The aim of this study was to evaluate the outcomes of pediatric MAAS through a multi-center data analysis. METHOD: Pediatric patients who underwent MAAS between January 2002 and December 2013 were retrospectively included. Data analysis was conducted using Spss software (Welch's t-test, X-square, Fisher tests, multiple regression model). RESULTS: Six European centers participated, 68 patients were included with mean age of 5.2 years (2 months-16 years). Lesion volume was of 18.1 cc (0.78-145.6), with a mean diameter of 2.8 cm (1.1-6.5). Localization was 50% left-sided masses, 45.6% right-side masses, and 4.4% bilateral. Histological examination revealed 36 neuroblastomas, 15 adenomas, nine pheochromocytomas, three ganglioneuromas, two ganglioneuroblastomas, one bilateral hyperplasia, one adrenocortical carcinoma, an alveolar sarcoma, and a calcification. Surgical access was transperitoneal in 63 (92.6%) and retroperitoneal in 5 (7.4%). Mean operative time was 170 ± 87 min (285 ± 30 min for bilateral lesions). Mean hospital stay was 4.2 ± 2.5 days. Complications included blood loss requiring transfusion in five patients (7.4%) and a diaphragmatic tear. Infiltration of surrounding structures correlated with intraoperative complication rate (p = 0.027) and operative time (p < 0.01). No mass rupture, conversion, or post-operative complications were observed. Median follow-up was 52 months (1-161). Two recurrences occurred in patients with pheochromocytoma. Age, weight, symptoms, characteristics at imaging, chemistry, volume, or histology, did not influence operative time, hospital stays, or complication rate. CONCLUSIONS: Pediatric MAAS was safe adopted for masses up to 145.6 cc, with a very low rate of complication. Conversion to open is not necessary even in the presence of infiltrations. MAAS should represent the first-line treatment for selected cases in centers experienced in laparoscopy.
Subject(s)
Adrenal Gland Neoplasms/surgery , Adrenalectomy/methods , Laparoscopy/methods , Minimally Invasive Surgical Procedures/methods , Adolescent , Adrenalectomy/adverse effects , Child , Child, Preschool , Europe , Female , Humans , Infant , Laparoscopy/adverse effects , Length of Stay/statistics & numerical data , Male , Minimally Invasive Surgical Procedures/adverse effects , Neoplasm Recurrence, Local/surgery , Operative Time , Postoperative Complications/epidemiology , Retrospective Studies , Treatment OutcomeABSTRACT
We report our decennial experience with 1161 newly-placed long-term central venous catheters inserted in 919 hematology-oncology patients for a total of 413,901 CVC-days of observation. Most of the CVCs were partially-implanted, open-ended, Broviac-Hickman type of CVC (95 %). One thousand and twenty-four complications were recorded equal to 2.47 per 1000 CVC-days. The frequency of complications per CVC, the rate of episodes per 1000 CVC-days, and removal rate were malfunction/occlusion 42 %, 1.18/1000, and 2.3 %; mechanical (dislodgement/rupture/kinking) 18.3 %, 0.51/1000, and 77.4 %; bacteremia 14.8 %, 0.42/1000, and 18.6 %; exit-site/tunnel infection 11.5 %, 0.32/1000, and 9.7 %; thrombosis 0.86 %, 0.02/1000, and 30 %; pneumothorax 0.52 %, 0.01/1000, and 0. In multivariate analysis, the risk factors were for mechanical complications, a younger age <6.1 years at CVC insertion (HR 1.8, p = 0.0006); for bacteremia, a double lumen CVC (HR 3.1, p < 0.0001) and the surgical modality of CVC insertion (HR 1.5, p = 0.03); for exit-site/tunnel infection, a double lumen CVC (HR 2.1, p = 0.0003) and a diagnosis of leukemia or lymphoma (HR 1.8, p = 0.01); for malfunction/occlusion, an age <6.1 years (HR 1.6, p = 0.0003), the diagnosis of leukemia or lymphoma (HR 1.9, p < 0.0001) and double lumen CVC (HR 1.33, p = 0.023). The cumulative incidence of premature CVC removal was 29.2 % and the risk factors associated with this event were the surgical modality of CVC insertion (HR 1.4, p = 0.0153) and an age at CVC positioning less than 6.1 years (HR 1.6, p = 0.0025). We conclude that a best-practice set of rules resulted in reduced CVC complications.
Subject(s)
Catheterization, Central Venous/adverse effects , Adolescent , Bacteremia/epidemiology , Bacteremia/etiology , Catheter-Related Infections/epidemiology , Catheter-Related Infections/etiology , Central Venous Catheters/adverse effects , Child , Child, Preschool , Equipment Failure , Female , Fungemia/epidemiology , Fungemia/etiology , Humans , Infant , Infant, Newborn , Kaplan-Meier Estimate , Leukemia/therapy , Lymphoma/therapy , Male , Neoplasms/therapy , Pneumothorax/epidemiology , Pneumothorax/etiology , Population Surveillance , Prospective Studies , Risk Factors , Thrombosis/epidemiology , Thrombosis/etiologyABSTRACT
BACKGROUND: Esophageal atresia (EA) is a congenital malformation of the upper gastrointestinal tract with an estimated prevalence varying from 1 in 2500 to 1 in 4500 births. The aim of this study was to describe the epidemiology of EA between 1981 and 2012 and evaluate patients' survival. METHODS: This study used data from a population-based Italian Congenital Malformation Registry. The survival status was ascertained by linking the registry records, vital records and the regional registries of patients. Kaplan-Meier methods were used to estimate survival probabilities up to 25 years and Cox proportional hazards regression was used to evaluate factors that affected survival. RESULTS: A total of 407 cases of EA were identified among 1,417,724 total births. After the exclusion of cases with chromosomal anomalies, 49.9% of the patients presented with at least one associated congenital anomaly. The 25-year survival probability was 85.1% (95% confidence interval [CI], 80.8-89.4), with most deaths occurring during the first months of life. Patients' characteristics associated with decreased survival probability were low birth weight (hazard ratio, 3.7; 95% CI, 1.7-8.3) and presence of additional major defects (hazard ratio, 2.8; 95% CI, 1.3-6.0). A significant improvement in survival over the decades was observed for patients with nonisolated EA. CONCLUSION: This study detected a significant improvement in survival of individuals with EA over the past decades and identified the strongest predictors of mortality. These results will be important for the planning of the clinical management and formulation of prognosis when EA is diagnosed in a newborn. Birth Defects Research (Part A) 106:542-548, 2016. © 2016 Wiley Periodicals, Inc.