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Vulvovaginal candidiasis (VVC) remains a prevalent fungal disease, characterized by challenges, such as increased fungal resistance, side effects of current treatments, and the rising prevalence of non-albicans Candida spp. naturally more resistant. This study aimed to propose a novel therapeutic approach by investigating the antifungal properties and toxicity of 2-hydroxychalcone (2-HC) and 3'-hydroxychalcone (3'-HC), both alone and in combination with fluconazole (FCZ) and clotrimazole (CTZ). A lipid carrier (LC) was also developed to deliver these molecules. The study evaluated in vitro anti-Candida activity against five Candida species and assessed cytotoxicity in the C33-A cell line. The safety and therapeutic efficacy of in vivo were tested using an alternative animal model, Galleria mellonella. The results showed antifungal activity of 2-HC and 3'-HC, ranging from 7.8 to 31.2 as fungistatic and 15.6 to 125.0 mg/L as fungicide effect, with cell viability above 80% from a concentration of 9.3 mg/L (2-HC). Synergistic and partially synergistic interactions of these chalcones with FCZ and CTZ demonstrated significant improvement in antifungal activity, with MIC values ranging from 0.06 to 62.5 mg/L. Some combinations reduced cytotoxicity, achieving 100% cell viability in many interactions. Additionally, two LCs with suitable properties for intravaginal application were developed. These formulations demonstrated promising therapeutic efficacy and low toxicity in Galleria mellonella assays. These results suggest the potential of this approach in developing new therapies for VVC.
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BACKGROUND: Older patients are at a higher risk of access site complications and bleeding. Systematic reviews and meta-analysis have highlighted the benefits of distal over proximal transradial access (mainly, lower rates of radial artery occlusion and faster hemostasis). We aimed to evaluate the feasibility and safety of distal transradial access (dTRA) for routine coronary procedures in older patients compared with non-older patients. METHODS: Retrospective analysis of a large and real-world sample of 5524 consecutive all-comers patients who underwent coronary procedures via dTRA were included in the DISTRACTION registry. RESULTS: In the older patients (greater than or equal to 65 years) group (n = 2594, 47%), there were higher rates of hypertension (83% vs 71.1%; P less than .0001), diabetes (45.1% vs 34.7%; P less than .0001), previous stroke (2.9% vs 2%; P=.0425), chronic heart failure (9.2% vs 7.1%; P=.0040), severe aortic valvar disease (4.2% vs 2.9%; P=.0070), chronic kidney disease stages 3 and 4 (8.1% vs 3.1%; P less than .0001), previous percutaneous coronary intervention (27.2% vs 24.5%; P=.0253), previous coronary artery bypass grafting (5.1% vs 2.2%; P less than .0001), cardiogenic shock at presentation (1.3% vs 0.4%; P=.0003), rotational atherectomy (0.7% vs 0.2%; P=.0050), and left main percutaneous coronary intervention (2.7% vs 1.5%; P=.0033). No significant differences were observed in the rates of access site crossovers. No major adverse cerebrovascular and cardiac events directly related to dTRA, no hand/thumb dysfunction or ischemia after any procedure, and no access site-related hematomas (early discharge after transradial stenting of coronary arteries greater than or equal to 2) were recorded. CONCLUSIONS: Despite more comorbidities, more complex coronary disease, and more challenging presentation, the adoption of dTRA as the default approach for routine coronary procedures in older patients, by proficient operators, appears to be safe and feasible.
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Aterectomia Coronária , Doença da Artéria Coronariana , Idoso , Humanos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Sistema de Registros , Estudos RetrospectivosRESUMO
BACKGROUND: Pleural effusion and empyema are frequent complications of acute bacterial pneumonia in children. To date, evidence regarding the optimal treatment of this condition is limited in the literature. METHODS: Patients with pleural effusion and empyema admitted at our Department of Pediatric Surgery over the last ten years were enrolled in this retrospective study, and successively compared with the clinical charts of patients treated before the introduction of a new diagnostic and therapeutic algorithm. In particular, primary outcomes investigated between pre- and postalgorithm period were the use of diagnostic tools and antibiotics, the need for additional therapeutic approaches, complications, and the length of stay. RESULTS: After the introduction of the new algorithm there were a decrease in the use of chest radiography for re-evaluation (100% vs. 79%, P=0.003), a more focused use of computed tomography (68% vs. 15%, P=0.001), and a decrease in the use of a second computed tomography (18% vs. 3%, P=0.07); in favor of an increase in the use of the ultrasound scan (40% vs. 100%, P=0.001). There was also a shift from the use of chest tube drainage alone to the use of drainage for urokinase administration (50% vs. 92.3%, P=0.001), and a statistically significant decrease in the need for video-assisted thoracoscopic surgery (25% vs. 7.7%, P=0.001). CONCLUSIONS: The introduction of a diagnostic and therapeutic algorithm for the management of pediatric pleural effusion and empyema has notably resulted in a decrease in the utilization of radiography and computed tomography and an increase in the use of ultrasonography, reducing unnecessary radiation exposure in children and overall costs.
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Background: The aim of this study was to evaluate the quality of our surgical informed consent and parents'/guardians' late recall of surgical procedures and risks of elective day surgery after pre-operative interview with surgeons. Methods: All parents/guardians of patients <18 years of age undergoing minor and intermediate elective procedures from January 15th to September 1st, 2022, were prospectively enrolled in the study. Before discharge, parents/guardians were asked to complete an in-house questionnaire regarding the duration of the consent procedure, duration of the interview, quality of the informative handouts, and their ability to recall the type of disease, type of surgical procedure, and surgical risks. Results: One hundred and two questionnaires were returned. In all cases, informed consent was obtained between 24 and 72â h prior to surgery. The following responses were collected: 98/102 (96%) parents/guardians reported that the duration of the consent process was adequate; 95/102 (93%) reported that the handouts were fully informative, and 7/102 (7%) reported that they were partially informative regarding explanation of the disease and surgical procedure; regarding complications, 93/102 (91%) perceived the handouts to be fully/partially informative, while 4/102 (4%) perceived the handouts to be poorly/non-informative, and 5/102 (5%) did not provide a response; 94/102 (92%) stated that they remembered the pathology, but only 87/94 (93%) recalled it correctly; 90/102 (88%) stated that they remembered the type of procedure, but only 76/90 (84%) recalled it correctly; and 53/102 (52%) stated that they remembered the surgical risks, but only 20/53 (38%) could recall more than one complication. Conclusions: Late recall of surgical complications by parents was poor despite the high perceived quality of the surgical risk handouts and medical interview. Implementation of expedient methods may improve overall comprehension and satisfaction of parents/guardians regarding the IC process. Further, more efforts should be made to develop standardized guidelines for an optimal IC process.
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Background and Objective: The use of robotic-assisted surgery (RAS) has increased more slowly in pediatrics than in the adult population. Despite the many advantages of robotic instruments, the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) still presents some limitations for use in pediatric surgery. This study aims to examine evidence-based indications for RAS in the different fields of pediatric surgery according to the published literature. Methods: A database search (MEDLINE, Scopus, Web of Science) was performed to identify articles covering any aspect of RAS in the pediatric population. Using Boolean operators AND/OR, all possible combinations of the following search terms were used: robotic surgery, pediatrics, neonatal surgery, thoracic surgery, abdominal surgery, urologic surgery, hepatobiliary surgery, and surgical oncology. The selection criteria were limited to the English language, pediatric patients (under 18 years of age), and articles published after 2010. Key Content and Findings: A total of 239 abstracts were reviewed. Of these, 10 published articles met the purposes of our study with the highest level of evidence and therefore were analyzed. Notably, most of the articles included in this review reported evidence-based indications in urological surgery. Conclusions: According to this study, the exclusive indications for RAS in the pediatric population are pyeloplasty for ureteropelvic junction obstruction in older children and ureteral reimplantation according to the Lich-Gregoire technique in selected cases for the need to access the pelvis with a narrow anatomical and working space. All other indications for RAS in pediatric surgery are still under discussion to date, and cannot be supported by papers with a high level of evidence. However, RAS is certainly a promising technology. Further evidence is strongly encouraged in the future.
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Introduction: Pilonidal disease (PD) is a common infectious and inflammatory condition affecting the gluteal cleft and sacrococcygeal region. The optimal treatment for PD remains controversial. While the open technique reduces the number of relapses compared to minimally invasive approaches, it is associated with a longer healing time. Reactive oxygen species are a key part of the normal wound-healing process. Herein, we reported our preliminary experience using a new oxygen-enriched oil-based product called NovoX for wound healing after open surgery for PD. Materials and methods: We used a new oxygen-enriched product for wound healing in three pediatric patients undergoing open surgical repair for PD between December 2021 and April 2022. During postoperative follow-up, healing time and the aesthetic result were evaluated. Results: Our preliminary study included three patients with chronic PD. The average follow-up time was 5 weeks, corresponding to the end of the healing process and the resumption of normal daily activities. Only one mild complication occurred during the study period. No short-term side effects were reported. The cosmetic result was reported as satisfactory. Conclusion: NovoX is easy to apply, safe, and effective for treating pediatric patients undergoing open surgical treatment for PD, leading to slightly faster wound healing with good aesthetic outcomes.
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Background: Esophageal atresia (EA) is a rare congenital malformation. A high incidence of GER unresponsive to medical management is noted with EA. Literature suggests that complications from GER can persist in adulthood. In paediatric age, laparoscopic treatment is a valid option even if recurrence rate is not negligible. Aims and Objectives: To evaluate our experience with gastro-esophageal reflux (GER) treatment after esophageal atresia (EA) repair. Materials and Methods: We retrospectively analysed 29 consecutive patients treated for EA at birth and studied for GER at our Institute in a period of 11 years. Results: 24/29 (82,7%) cases had symptoms of reflux, 17/29 (58,6%) cases were treated with laparoscopic fundoplication (LF). Three infants were younger than 6 months and had apparent life threatening events (ALTE) condition as principal indication for surgery. No intra-operative complications occurred. 3/17 LF had open surgical conversion due to technical problems. 2/17 cases required a second operation. At the last follow-up: (1) 6/17 (35,3%) of patients healed after the last operation, (2) 8/17 (47,1%) have GER improvement (four still in medical treatment), (3) 2/17 (11,8%) have persistent GER, (4) 1/17 (5,9%) died for causes not related to antireflux surgery. Conclusions: According to literature and to our retrospective analysis, LF for GER after EA repair is feasible, even if recurrence risk is not negligible. Infants less than 6 months old with associated conditions (malformations, gastrostomy/jejunostomy) seem to have a higher failure rate with a greater risk of conversion. Longer follow-up and multicenter experiences would guarantee an adequate surveillance for patients with EA.
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Atresia Esofágica , Refluxo Gastroesofágico , Laparoscopia , Adulto , Criança , Atresia Esofágica/complicações , Atresia Esofágica/cirurgia , Fundoplicatura , Refluxo Gastroesofágico/cirurgia , Gastrostomia/efeitos adversos , Humanos , Lactente , Recém-Nascido , Laparoscopia/efeitos adversos , Estudos RetrospectivosRESUMO
Introduction: The management of primary spontaneous pneumothorax (PSP) in pediatrics remains controversial. The aim of this study was to investigate the risk of recurrence after non-surgical treatment vs. surgery, the difference in the length of stay (LOS) between various treatment options, and the role of computed tomography (CT) in the management of PSP. Materials and Methods: We retrospectively reviewed patients admitted to our Pediatric Surgery Unit for an episode of PSP between June 2009 and July 2020. Medical records including clinical presentation at admission, diagnostics, treatments, complications, and LOS were collected. Results: Twenty-three patients (22 males and 1 female) were included in this study. Median age was 15.65 (range 9-18). Chest X-rays were performed in all patients and showed 5 small (22%) and 18 large (78%) PSP. Chest drain was used for large PSP (≥2 cm) if the patient was clinically unstable. Eleven patients (48%) were managed non-operatively with observation alone and a recurrence rate of 18%, chest drain was used in 11 patients with a recurrence rate of 36%, and surgery was deemed necessary as a first treatment choice in one case. Six patients (27%) had an episode of relapse after non-operative management or chest drain placement. Following surgery, a relapse occurred in 2 of the 6 patients. Chest drain insertion was associated with a longer LOS than observation alone (6.36 vs. 2.4 days), and surgery resulted in a longer LOS than other types of treatment (P = 0.001). Conclusion: According to our experience, small PSP or clinically stable larger PSP can be treated conservatively with observation alone. Operative management should be taken into consideration in children with large symptomatic PSP, persistent air leak, and/or relapse after chest drain insertion.
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Vulvovaginal candidiasis is a public health problem with a high incidence among female patients. Currently, there is an increase in the identification of Candida spp. resistant to current therapy, making it necessary to search for new therapeutic alternatives. The synergistic potential of curcumin with fluconazole is described in the literature. However, due to its high lipophilicity, it is necessary to use drug-delivery systems to adequately explore its potential, among which is the nanostructured lipid carrier. However, to date, there is no validated method of high-performance liquid chromatography for simultaneous determination of fluconazole and curcumin in the literature. Thus, the present work developed a high-performance liquid chromatography method for simultaneous determination of fluconazole and curcumin co-encapsulated in nanostructured lipid carrier which was validated according to the International Conference on Harmonization (Technical Requirements for Registration of Pharmaceuticals for Human Use) - Q2 (R1) and the Food and Drug Administration - Guidance for Bioanalytical Method. The method was applied to determine the encapsulation efficiency and drug-loading of curcumin and fluconazole in nanostructured lipid carriers. The developed method proved to be selective, precise, accurate, and robust for the simultaneous determination of both drugs, enabling the quantification of encapsulation efficiency and drug-loading of curcumin and fluconazole in nanostructured lipid carriers.
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Curcumina/análise , Fluconazol/análise , Lipídeos/química , Nanoestruturas/química , Cromatografia Líquida de Alta PressãoRESUMO
BACKGROUND: Circumcision refers to the removal of the skin covering the tip of the penis and is one of the most common surgical procedures performed in childhood. Even though circumcision is a well-standardized operation, several minor and major complications may be experienced by paediatric surgeons. Glans ischemia (GI) has been widely reported in the paediatric literature as a complication following circumcision. Nonetheless, etiopathogenesis of GI is not well defined and management guidelines are lacking. CASE SUMMARY: We describe our experience with this rare and scary complication using subcutaneous enoxaparin alone or in association with a topical vasodilator. CONCLUSION: Hypothetical causes and different management strategies are discussed.
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BACKGROUND: Sactosalpinx means a collection of fluid (serum, blood or pus) in the fallopian tube. CAH (Congenital Adrenal Hyperplasia) is a typical 46XX DSD (Disorder of Sex Development) due to a steroidogenic enzymatic defect. Both conditions are rare and can lead to reduced fertility rate. CASE PRESENTATION: We describe two post-menarche virgin girls with CAH who were hospitalized for acute abdomen due to laparoscopically confirmed sactosalpinx. Case 1 recovered after conservative management, case 2 after a second-look and bilateral salpingectomy. The first case consisted of right sactosalpinx and previous peritonitis reported; the second one of bilateral symptomatic pyosalpinx and previous vaginal stenosis. Recurrent abdominal pain persisted at follow-up in Case 1: post-operative MRI (Magnetic Resonance Imaging) showed bilateral hydrosapinx that disappeared at a following ultrasound scan control. Follow-up was uneventful 36 months after surgery in Case 2, except for the surgical revision of the vaginal introitus. CONCLUSIONS: CAH-sactosalpinx association is a very rare but not negligible event. We suggest a conservative approach for sactosalpinx if tubal and/or ovary torsion can be excluded. Pyosalpinx is more challenging to treat, but during pediatric age we suggest starting with a conservative approach, especially in patients with CAH who have a potential low fertility rate. Careful gynecological follow-up after menarche is recommended to rule out any further causes of infertility.
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Hiperplasia Suprarrenal Congênita/complicações , Doenças das Tubas Uterinas/terapia , Adolescente , Tratamento Conservador , Diagnóstico Diferencial , Doenças das Tubas Uterinas/diagnóstico por imagem , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Salpingectomia , UltrassonografiaRESUMO
BACKGROUND: In recent years, the use of restorative justice (RJ) and restorative practices (RP) in schools has grown rapidly. Understanding how theory and research address this topic is important for its practical implementation based on scientific knowledge. The aim of this article was to analyse the practices derived from RJ implemented in school and what kinds of results have been achieved. Starting from the analysis of the qualitative and quantitative research in the field, a systematic review was conducted on the last decade of studies using RJ and RP at every level of school education. METHODS: For this review, methods including the PRISMA guidelines, the PRISMA flow diagram, and qualitative synthesis were carried out. Scientific articles for the literature review were selected according to the following criteria: (1) publication date between the years 2010-2021; (2) student population aged 6-18 years; (3) publications in the English language; (4) articles directly accessible or accessible by contacting the author(s); 34 articles met the inclusion criteria. RESULTS: The most used RP in school are circles (n = 26), followed by restorative conferences (n = 17), peer mediation (n = 10), restorative conversations (n = 8), mediation (n = 7), community-building circles (n = 5). RP can improve the school climate, discipline, positive conflict management through actions that aim at preventing suspensions, exclusions, conflicts, and misbehaviours (e.g., bullying). RJ practices promote positive relationships between peers and between students and teachers, as well as to prosocial behaviours through the development of social and emotional skills. CONCLUSIONS: From the studies examined, a great interest in applying restorative justice and practices in schools clearly emerged. Discussions on the benefits and challenges of implementation were provided. However, there is still limited evidence in terms of direct correlation, which suggests further studies on the impact of RJ and RP in school settings.
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Bullying , Justiça Social , Humanos , Grupo Associado , Instituições Acadêmicas , EstudantesRESUMO
A neurogenic pathway, involving airway TRPV-1, has been implicated in acute cardiovascular events occurring after peaks of air pollution. We tested whether inhaled prostaglandin-E2 (PGE2) and bradykinin (BK) regulate TRPV-1 activity in vivo by changing cough response to capsaicin (CPS) and affecting heart rate variability (HRV), while also taking into account the influence of TRPV-1 polymorphisms (SNPs). Moreover, we assessed the molecular mechanism of TRPV-1 modulation in vitro. Seventeen healthy volunteers inhaled 100 µg PGE2, 200 µg BK or diluent in a randomized double-blind fashion. Subsequently, the response to CPS was assessed by cough challenge and the sympathetic activity by HRV, expressed by low (nLF) and high (nHF) normalized frequency components, as well as nLF/nHF ratio. Intracellular [Ca2+] was measured in HeLa cells, transfected with wild-type TRPV-1, pre-treated with increasing doses of PGE2, BK or diesel exhaust particulate (DEP), after CPS stimulation. Six functional TRPV-1 SNPs were characterized in DNA from each subject. Inhalation of PGE2 and BK was associated with significant increases in cough response induced by 30 µM of CPS (cough number after PGE2 = 4.20 ± 0.42; p < 0.001, and after BK = 3.64 ± 0.37; p < 0.01), compared to diluent (2.77 ± 0.29) and in sympathetic activity (nLF/nHF ratio after PGE2 = 6.1; p < 0.01, and after BK = 4.2; p < 0.05), compared to diluent (2.5-3.3). No influence of SNPs was observed on autonomic regulation and cough sensitivity. Unlike PGE2 and BK, DEP directly activated TRPV-1. Inhalation of PGE2 and BK sensitizes TRPV-1 and is associated with autonomic dysregulation of cardiac rhythm in healthy subjects.
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Bradicinina/farmacologia , Tosse/fisiopatologia , Dinoprostona/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Canais de Cátion TRPV/efeitos dos fármacos , Canais de Cátion TRPV/fisiologia , Administração por Inalação , Adulto , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/fisiologia , Bradicinina/administração & dosagem , Capsaicina/administração & dosagem , Capsaicina/efeitos adversos , Dinoprostona/administração & dosagem , Método Duplo-Cego , Feminino , Células HeLa , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Canais de Cátion TRPV/genéticaRESUMO
BACKGROUND: Cough is a common symptom in several respiratory diseases and may occur in healthy subjects as a defense mechanism against noxious inhalants. Cough response is mediated by transient receptor potential vanilloid-1 (TRPV1) expressed by C-fibers in the airways. Capsaicin (CPS) activates TRPV1 and is regularly used as a tool to study cough response. Although single nucleotide polymorphisms (SNPs) of TRPV1 are implicated in CPS binding, their role in cough response is not fully elucidated. AIMS: In this study we investigated the relationship between capsaicin cough challenge sensitivity and multiple TRPV1 polymorphisms. METHODS: The dose-response of cough induced by CPS inhalation was determined in 20 unselected healthy volunteers and the concentration of CPS causing two coughs (C2) was calculated. The SNPs I585V(rs8065080), T505A(rs17633288), T469I(rs224534), I315 M(rs222747), P91S(rs222749), and K2N(rs9894618) were characterized in blood DNA from each subject. The association between combinations of TRPV1 SNPs and CPS sensitivity of each subject was assessed by linear regression. RESULTS: All subjects were wild type for T505A and K2N, while they exhibited two to six SNPs with high capsaicin responsiveness. The major contribution to CPS sensitivity in vivo (C2) was due to four combined SNPs: 315 M, 585I, 469I and 91S (p = 0.015). We found, however, that the presence of a minimum of two polymorphisms, such as 91S combined with 315 M (p = 0.032) or 91S with 585I (p = 0.025), was sufficient to detect an effect on C2. CONCLUSION: Capsaicin cough challenge sensitivity in healthy subjects is dependent on multiple TRPV1 polymorphisms.
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Capsaicina/farmacologia , Tosse/genética , Polimorfismo de Nucleotídeo Único , Canais de Cátion TRPV/genética , Administração por Inalação , Adulto , Tosse/tratamento farmacológico , Voluntários Saudáveis , HumanosRESUMO
BACKGROUND: The choice of the sex of rearing in patients with ovotesticular differences of sex development (OT-DSD) is difficult. The final decision should be given by the patient himself or herself, but families' opinion is not to neglect especially when the diagnosis is precocious and the patient can't give the consent to medical or surgical procedures. How should we behave if the parents refuse to raise a child with genital ambiguity? CASE PRESENTATION: We describe and comment on our multidisciplinary approach in three patients with neonatal diagnosis of OT-DSD. The families expressed a strong desire for that which concerned the sex of rearing of their babies in contrast to the International trend of "wait and see". A specific counselling and a constant psychological support were given. CONCLUSIONS: Recent trends suggest of postponing surgery to involve the patient in the decision. Child's well-being is the goal of therapy. When medical and psychological support is not able to force parents to accept a child suffering from genital ambiguity, we think that it is better to opt for reversible medical/surgical treatments rather than allowing patients to grow up within a family that does not accept them.