The combined use of neutrophil gelatinase-associated lipocalin and brain natriuretic peptide improves risk stratification in pediatric cardiac surgery

Abstract Background: The aim of this study is to test the hypothesis whether the combined use of a cardio-specific biomarker, the brain natriuretic peptide (BNP) and a marker of early renal damage, the assay of urinary neutrophil gelatinase-associated lipocalin (uNGAL), may improve risk stratification in pediatric cardiac surgery. Methods: We prospectively enrolled 135 children [median age 7 (interquartile range 1–49) months] undergoing to cardiac surgery for congenital heart disease. All biomarkers were evaluated pre- and post-operatively at different times after cardiopulmonary-bypass (CPB): uNGAL at 2, 6 and 12 h; BNP at 12 and 36 h; serum creatinine at 2, 6, 12, and 36 h. Primary endpoints were development of acute kidney injury (AKI) (defined as 1.5 serum creatinine increase) and intubation time. Results: AKI occurred in 39% of patients (65% neonates and 32% older children, p=0.004). The peak of uNGAL values occurred more frequently at 2 h. uNGAL values at 2 h [median 28.2 (interquartile range 7.0–124.6) ng/L] had a good diagnostic accuracy for early diagnosis of AKI with an AUC (area under the curve) ROC (receiver operating characteristic) curve of 0.85 (SE 0.034). Using multivariable logistic regression analysis, development of AKI was significantly associated with uNGAL values at 2 h after CPB [OR=1.88 (1.30–2.72, p=0.001)], together with the CPB time and Aristotle score, as an index of complexity of the surgical procedure, while pre-operative BNP values were not. Furthermore, uNGAL and pre-operative BNP values (together with Aristotle score) were significantly associated with adverse outcome (longer intubation time and mortality). Conclusions: Pre-operative BNP and uNGAL values after surgery (together with the Aristotle score) were independently associated with a more severe course and worse outcome in children undergoing cardiac surgery for congenital heart disease.</jats:p

Involvement of Norepinephrine in the Control of Activity and Attentive Processes in Animal Models of Attention Deficit Hyperactivity Disorder

Functional and morphological studies in children affected by Attention Deficit Hyperactivity Disorder (ADHD) suggest a prefrontal cortex (PFc) dysfunction. This cortical region is regulated by subcortical systems including noradrenergic (NEergic), dopaminergic (DAergic), cholinergic, serotonergic, and histaminergic pathways. A wealth of data in humans and in animal models demonstrates altered dopamine (DA) regulation. Drugs that modulate norepinephrine (NE) transmission are also effective in ADHD patients, thus leading to the hypothesis of a NEergic disorder. This review covers the regulation of PFc functions by NE and the interaction between the NE and DA systems, as suggested by pharmacological, electrophysiological, morphological, and gene knock out (KO) studies. A negative feedback between NE and DA neurons emerges from KO studies because KO mice showing increased (NE transporter (NET) KO) or decreased (DBH and VMAT2 KO) NE levels are respectively associated with lower and higher DA levels. Locomotor activity can be generally predicted by the DA level, whereas sensitivity to amphetamines is by NE/DA balance. Some animal models of ADHD, such as spontaneously hypertensive rats (SHR), show alterations in the PFc and in the DA system. Evidence about a correlation between the NE system and hyper-locomotion activity in such animals has not yet been clarified. Therefore, this review also includes recent evidence on the behavioral effects of two NET blockers, reboxetine and atomoxetine, in two animal models of ADHD: SHR and Naples High Excitability rats. As these drugs modulate the DA level in the PFc, certain effects are likely to be due to a rebalanced DA system. We discuss the significance of the results for theories of ADHD and make suggestions for future experimentation

Aortopexy for Tracheomalacia in Children: A Systematic Review and Meta-Analysis

Introduction: Aortopexy is the most common surgical option for the treatment of severe tracheomalacia (TM) in children. Despite being described over 75 years ago, several aspects of the procedure remain controversial. Materials and Methods: A systematic review of aortopexy was conducted following the PRISMA guidelines. All original articles describing at least one case of aortopexy performed in children for the treatment of TM were included. Patients’ characteristics, surgical indications, approaches and details were collected. Outcomes were reviewed, and potential factors associated with procedural success were investigated. Results: Of 243 papers, 17 were included in this review, encompassing a total of 473 patients who underwent aortopexy. Of these, 65.3% were male, with a mean age at surgery of 12.2 months (5 days–18 years). Primary TM accounted for 7.9% of cases, while 92.1% were secondary to other anomalies, including esophageal atresia (54.1%), aberrant innominate artery (16.1%) and vascular rings (8.3%). There is a general consensus on the surgical indication for TM with severe symptoms, although the definition of severity is not well established. Overall success was 84%, but 40.8% of patients experienced some persistent symptoms. Sternotomy and thoracotomy were the most successful approaches (92.6% and 84.2%, respectively). Thoracoscopy had a similar success rate to sternotomy when pericardiotomy, thymectomy and pledgeted suture were performed (86.4% vs. 92.6% p = 0.41). Conclusions: Aortopexy is associated with good outcomes, but no evidence-based guidelines are currently available. Success appears to be associated with specific surgical steps rather than the surgical approach. Prospective studies are desirable for establishing precise guidelines

CD28 individual signaling up-regulates IL-22 expression and IL-22-mediated effector functions in human T lymphocytes

IL‐22 is a member of the IL‐10 cytokine family involved in host protection against extracellular pathogens, by promoting epithelial cell regeneration and barrier functions. Dysregulation of IL‐22 production has also frequently been observed in acute respiratory distress syndrome (ARDS) and several chronic inflammatory and autoimmune diseases. We have previously described that human CD28, a crucial co‐stimulatory receptor necessary for full T cell activation, is also able to act as a TCR independent signalling receptor and to induce the expression of IL‐17A and inflammatory cytokines related to Th17 cells, which together with Th22 cells represent the main cellular source of IL‐22. Here we characterized the role of CD28 autonomous signalling in regulating IL‐22 expression in human CD4+ T cells. We show that CD28 stimulation in the absence of TCR strongly up‐regulates IL‐22 gene expression and secretion. As recently observed for IL‐17A, we also found that CD28‐mediated regulation of IL‐22 transcription requires the cooperative activities of both IL‐6‐activated STAT3 and RelA/NF‐κ transcription factors. CD28‐mediated IL‐22 production also promotes the barrier functions of epithelial cells by inducing mucin and metalloproteases expression. Finally, by using specific inhibitory drugs, we also identified CD28‐associated class 1A phosphatidylinositol 3‐kinase (PI3K) as a pivotal mediator of CD28‐mediated IL‐22 expression and IL‐ 22‐dependent epithelial cell barrier functions

CD28 autonomous signaling orchestrates IL-22 expression and IL-22-regulated epithelial barrier functions in human T lymphocytes

IL-22 is a member of the IL-10 cytokine family involved in host protection against extracellular pathogens, by promoting epithelial cell regeneration and barrier functions. Dysregulation of IL-22 production has also frequently been observed in acute respiratory distress syndrome (ARDS) and several chronic inflammatory and autoimmune diseases. We have previously described that human CD28, a crucial co-stimulatory receptor necessary for full T cell activation, is also able to act as a TCR independent signaling receptor and to induce the expression of IL-17A and inflammatory cytokines related to Th17 cells, which together with Th22 cells represent the main cellular source of IL-22. Here we characterized the role of CD28 autonomous signaling in regulating IL-22 expression in human CD4+ T cells. We show that CD28 stimulation in the absence of TCR strongly up-regulates IL-22 gene expression and secretion. As recently observed for IL-17A, we also found that CD28-mediated regulation of IL-22 transcription requires the cooperative activities of both IL-6-activated STAT3 and RelA/NF-κB transcription factors. CD28-mediated IL-22 production also promotes the barrier functions of epithelial cells by inducing mucin and metalloproteases expression. Finally, by using specific inhibitory drugs, we also identified CD28-associated class 1A phosphatidylinositol 3-kinase (PI3K) as a pivotal mediator of CD28-mediated IL-22 expression and IL-22–dependent epithelial cell barrier functions

Robotic Single-Port da Vinci Surgical System (SP1098) in Gynecologic Surgery: A Systematic Review of Literature

Background: Recently, new surgical systems less invasive than standard laparoscopy have been developed. Among these, robotic single site surgery is playing a pivotal role. In this field, the da Vinci SP (Single-Port) Surgical System (SP1098) is one of the newest surgical technology that presents innovative characteristics that may lead to better surgical outcomes. Few groups have already published their experience and results with this system in gynecology. Methods: The aim of the present systematic review was to provide a comprehensive overview of the status and applications of da Vinci SP1098 in gynecologic surgery. A systematic review of the literature was performed. Studies were identified until September 2022. Results: Six studies were included, reporting a total of 211 patients. The indication for surgery was both benign and malignant disorders. In terms of operative outcomes, the mean/median docking time varied from 2.1 to 5 min while mean/median operating time from 86.5 to 245 min. There was no conversion to multi-port laparoscopy or laparotomy and no major complications related to SP surgery. Conclusions: In conclusion, the preliminary and limited data available regarding the da Vinci SP1098 Surgical System suggest the technical feasibility and safety for its use in gynecologic surgery, with minimal alteration of the surgical technique

Dienogest vs. combined oral contraceptive: A systematic review and meta-analysis of efficacy and side effects to inform evidence-based guidelines

Introduction: Dienogest is a synthetic fourth-generation progestin that has been approved for the medical treatment of endometriosis, and its efficacy on pain symptoms and quality of life is well established even in the long term. Nowadays, only a few controlled trials evaluating the safety of dienogest compared with other hormonal therapies have been published. This systematic review and meta-analysis aims to compare efficacy and tolerability data between dienogest and combined oral contraceptives (COC) in patients taking hormonal therapy for endometriosis treatment in order to inform evidence-based guidelines. Material and Methods: PubMed (Medline), Web of Science, and Google Scholar were systematically searched from the inception of each database until October 2024. Selection criteria included any articles comparing efficacy outcomes and at least one tolerability data between dienogest and COC in patients diagnosed with endometriosis. Studies comparing COC containing Dienogest or another type of hormonal treatment were excluded. A random-effects meta-analysis was conducted if adequate data were available from at least three studies, reporting pooled mean differences and odds ratios between groups using Review Manager V.7.9.0. PROSPERO registration number: CRD42024598455. Results: A total of four randomized control trials and one observational study were included, showing moderate risk at bias assessment. Meta-analysis did not show any statistical difference in improving pelvic pain after treatment [CI 95% (−1.45–1.17); I2 = 86%; p = 0.84]. In contrast, dyspareunia after treatment was significantly lower in the COC group [CI 95% (0.64–1.33); I2 = 0%; p < 0.00001]. No statistical difference was found in terms of vaginal bleeding [OR = 0.88; CI 95% (0.39–1.96); I2 = 41%; p = 0.75], nausea and vomiting [OR = 0.51; CI 95% (0.16–1.63); I2 = 67%; p = 0.26], headache [OR = 0.91; CI 95% (0.38–2.21); I2 = 59%; p = 0.84], hot flushes [OR = 1.16; CI 95% (0.54–2.48); I2 = 0%; p = 0.71], and hair loss [OR = 1.69; CI 95% (0.52–5.53); I2 = 46%; p = 0.39]. Treatment discontinuation rate was similar between groups. Conclusions: Dienogest is comparable to COC in terms of efficacy and tolerability. The therapeutic choice should be based on the patient's preference, clinical history, and experience

The exciting journey of progress: Exploring FIGO 2023 staging for endometrial cancer at a leading ESGO institution

Introduction: The 2023 FIGO staging of endometrial cancer integrates tumor grade and histology along with molecular features that recognize the prognostic significance of p53 and POLE mutations, accounting for potential conflicts such as lymphovascular space invasion and subserosal invasion. Materials and methods: In this single-institution retrospective study, data were collected on 229 endometrial cancer patients from January 2020 to September 2024 and re-stage them according to FIGO 2023 criteria. Results: From FIGO stage 2009 IA, 70 patients do not cross stage (21 are FIGO 2023 IA1 and 49 IA2), 8 patients are upgraded to FIGO IC because of aggressive histotype; 1 is upstaged because of substantial LVSI, and 12 because of aggressive myoinfiltrating tumors (23 % of upstaging). From FIGO 2009 stage IB 34 patients remain in FIGO 2023 IB, while 5 become stage IIB (LVSI) and 27 IIC (aggressive myoinfiltrating), for a total of 32 upstages (48 % of upstaging). Within FIGO 2009 stage II, no proper upstage was possible. We observed a statistical correlation between stages and BMI, as well as between stages and age, for both FIGO 2009 (p = 0.009 and p < 0.001 respectively) and FIGO 2023 (p = 0.002 and p = 0.003 respectively) classifications. Additionally, a correlation was found between tumor grade and BMI (p = 0.02). Conclusions: The FIGO 2023 staging system is gaining importance as recent studies highlight the role of molecular classification in prognosis and personalized therapy. Updating our study's follow-up data will clarify its impact in clinical practice

Mesonephric-Like Adenocarcinomas a Rare Tumor: The Importance of Diagnosis

Mesonephric-like adenocarcinomas (MLA) are rare neoplasms that arise in the uterine body and ovary and have been added to the World Health Organisation’s recent 2020 classification of female genital cancers. The pathogenesis of MLA is unknown and it remains debated whether they represent mesonephric carcinomas (Wolffian) arising in the endometrium/ovary or endometrioid carcinomas (Müllerian) closely mimicking mesonephric carcinomas. Here we report the case of a 57-year-old woman with an initial misdiagnosis of endometrioid adenocarcinoma on diagnostic biopsy. The patient came to our clinical evaluation for the appearance of menometrorrhagia complicated by anemia for several months. Therefore, she underwent pelvic echo-flowmetry, with indication for diagnostic hysteroscopy with endometrial biopsy, which yielded a positive result for endometrioid endometrial adenocarcinoma. Following staging CT scan and targeted examinations on pulmonary findings, the patient underwent surgery with surprise of definitive diagnosis deponent for endometrial MLA. Our intention is to establish a brief review of the scientific evidence in the literature and the tools available for a correct histological diagnosis, in the light of the scant anatomopathological evidence. Our question gives rise to the motive for the publication: is immunohistochemistry the right way to resolve the diagnostic error at histology, which is usually the only source of diagnostic certainty? This case is intended to alert of diagnostic error that risked having the patient treated as a neoplasm with a favorable prognosis and low degree of aggressiveness instead of for a very aggressive and poor prognosis tumor such as MLA

Primary flap closure of perineal defects to avoid empty pelvis syndrome after pelvic exenteration in gynecologic malignancies: An old question to explore a new answer

: Pelvic exenteration (PE) is a radical oncological surgical procedure proposed in patients with recurrent or persistent gynecological cancers. The radical alteration of pelvic anatomy and of pelvic floor integrity can cause major postoperative complications. Fortunately, PE can be combined with reconstructive procedures to decrease complications and functional and support problems of pelvic floor, reducing morbility and mortality and increasing quality of life. Many options for reconstructive surgery have been described, especially a wide spectrum of surgical flaps. Different selection criteria have been proposed to select patients for primary perineal defect flap closure without achieving any strict indication of the best option. The aim of this review is to focus on technical aspects and the advantages and disadvantages of each technique, providing an overview of those most frequently used for the treatment of pelvic floor defects after PE. Flaps based on the deep inferior epigastric artery, especially vertical rectus abdominis musculocutaneous (VRAM) flaps, and gracilis flaps, based on the gracilis muscle, are the most common reconstructive techniques used for pelvic floor and vaginal reconstruction. In our opinion, reconstructive surgery may be considered in case of total PE or type II/III PE and in patients submitted to prior pelvic irradiation. VRAM could be used to close extended defects at the time of PE, while gracilis flaps can be used in case of VRAM complications. Fortunately, numerous choices for reconstructive surgery have been devised. As these techniques continue to evolve, it is advisable to adopt an integrated, multi-disciplinary approach within a tertiary medical center