Resveratrol in the treatment of asthma based on an animal model.

Resveratrol is a natural polyphenol found, for example, in red wine, grapes or nuts. One of the resveratrol's health properties is a cardioprotective activity - it is believed that resveratrol is responsible for the French paradox and anticancer activity. Moreover, the effectiveness of resveratrol in the treatment of asthma is confirmed by multiple research. Resveratrol displays a multiway impact on the reduction of the symptoms of the disease which contributes to the alleviation of inflammation i.a. by: inhibition of cellular infiltration, suppression of oxidative stress, reduction in the volume of mucus, relaxation of smooth muscle, stalling of the fibrosis affecting the respiratory tract or counteracting bronchial hyperresponsiveness. Resveratrol reduces the concentration of eosinophils, pro-inflammatory interleukins and interferes with many signal transduction pathways. In case of concomitance of obesity, resveratrol alleviates the course of asthma. The review juxtaposes the mechanisms of resveratrol activity and presents the results of the published research conducted on rodents.

Ecthyma gangrenosum as a serious complication of Pseudomonas aeruginosa infection in departments of paediatric oncology.

In most cases ecthyma gangrenosum is a consequence of Pseudomonas aeruginosa bloodstream infection in immunodeficient patients. This bacterium is characterized by multi-drug resistance and has a number of mechanisms that allow it to survive even in extreme conditions. The disease is characterized by an aggressive course involving the skin and mucous membranes, leading to ulceration with signs of necrosis within 12 to 24 h. Treatment includes targeted antibiotic therapy and surgical cleansing of the wound. If the perianal area is occupied, a colostomy may be performed. Prevention of bacterial infections involves taking special precautions when handling a patient with immunodeficiency.

Metal allergy after the Nuss procedure for pectus excavatum: a review.

Minimally invasive repair of pectus excavatum (MIRPE) technique (the Nuss procedure) is a minimally-invasive method that is commonly used in the treatment of pectus excavatum. An allergic reaction to the metal alloy bar that is implanted in the thorax during the procedure is a reported complication. We briefly review current literature concerning epidemiology, mechanisms and research results of allergic reactions after Nuss bar implantation. This allergic reaction occurs in approximately 2.7% of patients and is caused by metals used in the medical implant. The most common symptoms include fever and skin lesions such as allergic dermatitis. Elevated levels of C-reactive protein is a frequent finding in laboratory tests. In order to minimize the risk of such complications, taking a detailed allergy-based medical history and conducting allergy tests, i.e. patch test are required. Allergic reactions can be managed with conservative treatment such as general or topical glucocorticosteroid therapy and antihistamine agents. Severe allergic reactions can be addressed by implant revision, replacement of the steel bar with a titanium substitute or removal of the stabilization at all. Although the risk of an allergic reaction to titanium is smaller it still exists, the titanium substitute is not routinely used due to its higher cost and lesser plasticity which has a negative impact on matching a stabilizing bar during the surgery. Surgeons treating pectus excavatum should remember about the possible allergic reactions after implantation of the metal bar and be familiar with methods of diagnosis and treatment of those complications.

Treatment of haemangiomas using propranolol in paediatric patients: a retrospective cohort study.

INTRODUCTION: Haemangioma, one of the most common benign neoplasms of early childhood, is a significant clinical problem due to cosmetic reasons but also because of possible health complications. AIM: Presentation of the method and results of treatment of infantile haemangiomas (IHs) using propranolol in a maximum dose of 3 mg/kg/day. MATERIAL AND METHODS: In 2013 to 2018 there were 108 patients with IHs multidisciplinary diagnosed and treated. 77 of them were girls and 31 were boys; all were between the ages of 2 and 21 months (mean: 6.87 months). Lesions were most often located in the head region (n = 73). The main imaging study assessing the arteriovenous flow was USG, which was used to assess the size of haemangioma and its regression or progression. Also, coagulation parameters were analysed using laboratory tests. RESULTS: Reduction of lesions occurred in 103 of 108 patients, which results in a percentage score above 95. In 19 patients, after completion of treatment, there were abnormalities of coagulation in laboratory tests whereas before the treatment, these abnormalities occurred in 82 patients. The average duration of treatment was longer than 12 months and the maximum dose of propranolol of 3 mg/kg/day was achieved after 3 to 5 months of treatment. Side effects occurred totally in 19 patients, with night anxiety and nightmares being the most common. CONCLUSIONS: After achieving the maximum dose of the drug later than recommended in the Recommendation of the Polish Haemangioma and Vascular Malformations Group criteria, there was no need for longer therapy, while the effectiveness of the treatment remained unchanged. Side effects that occurred were not life-threatening or detrimental to the health of patients.

Age-dependent determinants of infectious complications profile in children and adults after hematopoietic cell transplantation: lesson from the nationwide study.

Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fungal disease (IFD) in children and adults after hematopoietic cell transplantation (HCT) were compared in 650 children and 3200 adults in multicenter cross-sectional nationwide study. Infections were diagnosed in 60.8% children and 35.0% adults, including respectively 69.1% and 63.5% allo-HCT, and 33.1% and 20.8% auto-HCT patients. The incidence of bacterial infections was higher in children (36.0% vs 27.6%; p < 0.0001). Infections with Gram-negative bacteria were more frequent than Gram-positives in adults (64.6% vs 44.8%; p < 0.0001). Outcome of bacterial infections was better in children (95.5% vs 91.4%; p = 0.0011). The IFD incidence (25.3% vs 6.3%; p < 0.0001) and outcome (88.0% vs 74.9%; p < 0.0001) were higher in children. The incidence of viral infections was higher in children after allo-HCT (56.3% vs 29.3%; p < 0.0001), and auto-HCT (6.6% vs 0.8%; p < 0.0001). Outcome of viral infections was better in children (98.6% vs 92.3%; p = 0.0096). Infection-related mortality was 7.8% in children and 18.4% in adults (p < 0.0001). No child after auto-HCT died of infection. Adult age, mismatched transplants, acute leukemia, chronic GVHD, CMV reactivation, infection with Gram-negatives, and duration of infection > 21 days were risk factors for death from infection. In conclusion, pediatric patients have 2.9-fold higher incidence and 2.5-fold better outcome of infections than adults after HCT.

Epidemiology and outcome of invasive fungal disease in children after hematopoietic cell transplantation or treated for malignancy: Impact of national programme of antifungal prophylaxis.

The objective of the study was the analysis of incidence and outcome of invasive fungal disease (IFD) in children treated for malignancy (PHO, paediatric hematology-oncology) or undergoing hematopoietic cell transplantation (HCT) over a period of six consecutive years in nationwide study. A total number of 5628 patients with newly diagnosed malignancies and 971 patients after HCT (741 allo-HCT and 230 auto-HCT) were screened for infectious complications in biennial reports. IFD incidence was lower among PHO patients: 8.8% vs 21.2% (P < .0001) and survival from IFD was better: 94.2% vs 84.1% (P < .0001). Auto-HCT patients had lower incidence (10.9% vs 24.4%) and lower mortality than allo-HCT patients. Introduction of national antifungal prophylaxis programme in HCT and acute leukaemia patients decreased incidence of IFD in HCT (from 23.1% to 13.4%) and AML on conventional chemotherapy (from 36% to 23%) but not in ALL patients during chemotherapy. In multivariate analysis, the incidence of IFD was higher in patients after HCT, diagnosed for ALL, AML or NHL, and in patients > 10 years old. Factors contributing to death with infection were as follows: undergoing HCT, diagnosis of acute leukaemia (ALL or AML) and duration of treatment of infection > 21 days. In conclusion, the incidence of IFD in allo-HCT and in AML patients on chemotherapy has decreased after introduction of national programme of antifungal prophylaxis, while the incidence of IFD in ALL patients on chemotherapy did not change significantly. The outcome of IFD both in PHO and HCT patients has largely improved in comparison with historical international data.

Complex profile of multiple hepatobiliary and gastrointestinal complications after hematopoietic stem cell transplantation in a child with Nijmegen breakage syndrome.

Patients with Nijmegen breakage syndrome (NBS) can develop life-threatening immunodeficiency, which should be treated with hematopoietic stem cell transplantation (HSCT). We report the case of a 14-year-old girl with NBS who due to an increasing number of severe complications was referred for HSCT from a matched unrelated donor. After reduced-intensity conditioning and transplantation of peripheral blood hematopoietic cells, during the early post-transplant period (days 0-30), the girl suffered from severe mucositis, fever episodes, mild acute renal injury and facial vasculitis. All these complications were managed successfully. During the intermediate post-transplant period (days 30-100) a number of hepatic and gastrointestinal complications occurred, including cholecystitis, cholelithiasis with choledocholithiasis, pancreatitis as well as acute bleeding from the lower gastrointestinal tract caused by rectal and recto-sigmoid junction ulcers. All the obstacles were obviously attributable both to the primary congenital disease, its complications, and transplantation itself. We overcame these complications and treated the patient with the best possible and safe methods. The multidisciplinary approach based on combined surgical, endoscopic and conservative management of multiple post-transplant complications was successful for the patient.

Endocrine systems of the skin.

Apart from its protective function, the skin is also both hormonally and metabolically active. Many hormones are produced in the skin and the regulation of these changes is controlled, as are other organs, by the pituitary gland and hypothalamus. Under the influence of stress factors such as ultraviolet radiation, many reactions are stimulated. After exposure to light in keratinocytes apart from eumelanin, also proopiomelanocortin, dopamine, and opioid substances - ß-endorphins are produced. The skin also has a hypothalamic-pituitary-adrenal axis homolog. A corticotropin-releasing hormone is produced and reacts with its skin receptors that lead to, among others, increasing vascular permeability or induce keratinocytes differentiation. A similar homologous system found in skin structures is the hypothalamic-pituitary-thyroid axis, which is expressed by the presence of e.g. thyroid-stimulating hormone (TSH) receptors or thyroglobulin genes. Our review presents selected hormonal skin systems, reactions within them and their products.

Systemic lupus erythematosus of the urinary tract: focus on lupus cystitis.

Systemic lupus erythematosus (SLE) frequently manifests as urinary tract disease, most commonly in the form of lupus nephritis. Bladder involvement in the disease course takes a subclinical form and may affect both children and adults. Lupus cystitis can precede SLE diagnosis and may present with very unspecific urinary and digestive tract symptoms or no symptoms at all. The exact mechanism of bladder inflammation in lupus is not fully understood; however, histopathological studies suggest a possible role of immune complex-mediated small vessel vasculitis. Lupus cystitis is a rare SLE manifestation, but poses a challenge for physicians, due to its complex diagnostics and treatment.

Use of diagnostic imaging in the evaluation of gastrointestinal tract duplications.

BACKGROUND: Gastrointestinal tract duplication is a rare malformation associated with the presence of additional segment of the fetal gut. The aim of this study was to retrospectively review clinical features and imaging findings in intraoperatively confirmed cases of gastrointestinal tract duplication in children. MATERIAL/METHODS: The analysis included own material from the years 2002-2012. The analyzed group included 14 children, among them 8 boys and 6 girls. The youngest patient was diagnosed at the age of three weeks, and the oldest at 12 years of age. RESULTS: The duplication cysts were identified in the esophagus (n=2), stomach (n=5), duodenum (n=1), terminal ileum (n=5), and rectum (n=1). In four cases, the duplication coexisted with other anomalies, such as patent urachus, Meckel's diverticulum, mesenteric cyst, and accessory pancreas. Clinical manifestation of gastrointestinal duplication cysts was variable, and some of them were detected accidently. Thin- or thick-walled cystic structures adjacent to the wall of neighboring gastrointestinal segment were documented on diagnostic imaging. CONCLUSIONS: Ultrasound and computed tomography are the methods of choice in the evaluation of gastrointestinal duplication cysts. Apart from the diagnosis of the duplication cyst, an important issue is the detection of concomitant developmental pathologies, including pancreatic heterotopy.

Use of Staged vs. Primary Repair in Thoracoscopic Esophageal Atresia Repair.

INTRODUCTION: Morbidity after thoracoscopic primary repair of esophageal atresia (EA) is still high in many centers. We retrospectively assessed the outcomes of a center-specific standardized approach in a group of newborns with EA that had been classified into one of two surgical management groups. METHODS: 38 consecutive newborns with EA (median birth weight: 2570 g, range: 1020-3880) were treated between 2013 and 2022. The patients were classified into one of two groups: one-stage or multi-stage approach. The decision was based on the patients' general condition, the results of preoperative tests and/or by local conditions during thoracoscopy. RESULTS: Thirty patients (all with type C EA) underwent primary esophageal anastomosis and 8 patients (21%) underwent multi-stage surgery and delayed anastomosis. The decision to take a multi-stage approach was made in the following cases: hemodynamic instability (n = 3), severely hypoplastic (up to 2 cm) distal esophagus (n = 1), extremely high position of the proximal esophagus (n = 2) and in all patients with type A EA (n = 2). In the multi-stage group, the second-stage procedure was performed after a median of 13 days (range: 7-42). Overall survival for all patients was 89%, with a median follow-up of 4.5 years. We did not note either anastomotic leaks or conversion to the open technique in our cohort. CONCLUSION: In selected cases, the multi-stage approach can affect patient safety in terms of surgical morbidity. Considering multi-stage correction of EA in advance can positively affect outcomes, especially in terms of lower rates of anastomosis leakage and of conversion to open surgery. LEVEL OF EVIDENCE: III.

Short-term and mid-term effects of thoracoscopic repair of esophageal atresia: No anastomotic leaks or conversions to open technique.

The frequency rate of esophageal anastomosis leaks after thoracoscopic correction of esophageal atresia (EA) in the current literature is reported as 5.6%-24.7% and a conversion rate of 2%-53%. The objective of this retrospective study was to examine the characteristics of EA and analysis of the safety and efficacy of EA repair with the use of the thoracoscopic approach in a single academic center, as well as risk factors analysis in the context of short-term and mid-term follow-up status. A retrospective analysis of the management of all consecutive newborns affected by EA hospitalized in our department over a period between 2013 and 2022, including preoperative, perioperative, and postoperative management, together with the outcome, complications and long-term follow-up status was performed. A total of 38 patients with a median birth weight of 2,570 g (range; 1,020-3,880) were treated over the study period, including 30/38 (78.9%) with additional congenital anomalies. Overall, 30 patients underwent primary anastomosis of the esophagus and eight underwent a multistaged procedure, with or without an initial ligation of the tracheoesophageal fistula and delayed primary anastomosis. Overall survival for all patients was 0.894 ± 0.050, with a median follow-up of 4.5 years. We noted neither anastomotic leaks nor conversions to open technique in our cohort. Implementation of vancomycin prophylaxis was successful in preventing postoperative central venous access-related infectious complications. At the end of the follow-up, 85% of patients have a Lansky performance score ≥80. Risk factors analysis for length of hospitalization, overall survival, Lansky performance status, and neurological impairment were analyzed. In conclusion, we have found that the outcome of thoracoscopic repair of EA in terms of surgery-dependent morbidity (anastomosis leakage, conversion rate to open surgery), provides benefit to those previously reported in the literature, regardless of the prognostic criteria of the classification system.

A Severe Systemic Infection in a 14-Year-Old Boy That Took Place during the COVID-19 Pandemic.

INTRODUCTION: Since March 2020, the COVID-19 pandemic has been a global talking point. Access to health care has become more difficult, and such an obstacle increase the risk of inadequate medical care, especially among paediatric patients. CASE: This report describes the case of a previously healthy teenager who was staying home for 2 months due to a strict lockdown period in the COVID-19 pandemic and was admitted to hospital for fever, nausea and lumbar pain. He was diagnosed consecutively with meningitis, sepsis, paraspinal abscesses and endocarditis. Further investigation did not reveal any risk factors or immunodeficiency in the patient. DISCUSSION: Sepsis is defined as the presence of systemic inflammatory response syndrome (SIRS) associated with a probable or documented infection. It is the leading cause of death from infection, especially if not recognized and treated quickly. Sepsis may lead to various complications, such as infective endocarditis, meningitis and abscesses. Although such complications may initially be latent, they can promote internal organ dysfunction and the possibility of their presence should be considered in any patient with systemic infection. Any child with a fever should be treated as one with the possibility of developing a severe infection. CONCLUSION: The presented case shows that even a previously healthy child staying in long-term home isolation can develop a severe infection with multiorgan complications, and the COVID-19 pandemic should not extend the diagnostic process in patients with symptoms of infection.

Clinical Spectrum and Outcomes of Neonatal Necrotizing Enterocolitis.

BACKGROUND/AIM: The objective of the study was analysis of risk factors associated with outcome of necrotizing enterocolitis (NEC) in infants in a single-center study. PATIENTS AND METHODS: All consecutive infants hospitalized for NEC over a period of 6 years were retrospectively analyzed for clinical course, infections, treatment and outcome. RESULTS: Out of 76 patients, surgical management was applied in 56 (53 exploratory laparotomy, three initial peritoneal drain placement) and in 20 there was only a conservative approach. Segmental intestinal resection was performed in 41 patients. Survival from NEC in our cohort was 79%. We found that independent adverse risk factors of outcome of newborns and infants with NEC were gut perforation, infection, abdominal wall erythema, and development of acute kidney injury. CONCLUSION: We underline the value of both surgical and conservative approach with careful management in this cohort of patients.

Berberine in the Treatment of Diabetes Mellitus: A Review.

Berberine is an alkaloid found in plants. It has neuroprotective, anti-inflammatory and hypolipidemic activities. The research proves that it also strongly impacts carbohydrate metabolism. The compound also protects pancreatic ß-cells and increases sensitivity to insulin in peripheral tissues via the induction of GLUT-1, GLUT-4 and insulin type 1 (Ins-1) receptors activity. It also stimulates glycolysis and leads to a decrease in insulin resistance by macrophages polarization, lipolytic processes induction and energy expenditure enhancement (by reducing body mass and limiting insulin resistance caused by obesity). In liver berberine inhibits FOX01, SREBP1 and ChREBP pathways, and HNF-4α (hepatocyte nuclear factor 4 alpha) mRNA that hinder gluconeogenesis processes. In the intestines it blocks α-glucosidase contributing to glucose absorption decrease. Its interference in intestinal flora reduces levels of monosaccharides and suppresses diabetes mellitus complications development.

Management with wrap disruption after Nissen fundoplication in a child with gastro-oesophageal reflux after congenital oesophageal atresia: A case report and minireview.

Pathological gastro-oesophageal reflux (GER) is one of the most common complications that results in the aftermath of treatment of congenital oesophageal atresia (EA). The aim of this study is to present a case of a 7-year-old girl with severe gastro-oesophageal reflux disease (GERD) operated on in the neonatal period due to EA with a lower tracheo-oesophageal fistula (TEF). The patient, despite the use of adequate conservative treatment, clinically and in the endoscopic examination was diagnosed with severe oesophagitis (LA-D in the Los Angeles classification). After a laparoscopic fundoplication by the Nissen method at the age of 4, a transient clinical improvement and a reduction of inflammatory lesions in the oesophagus were obtained. Three years after the procedure, the patient presented with deterioration of GERD clinical symptoms in the form of: regularly occurring vomiting with periodic admixture of fresh blood, recurrent cough, symptoms of dysphagia and failure to thrive. An upper gastrointestinal endoscopy (upper GI endoscopy) revealed significant progression of inflammatory changes in the oesophagus and the two-level oesophageal stricture together with endoscopic signs of wrap disruption. Based on the conducted diagnostics, the girl was qualified for surgical revision. The diagnosis was confirmed intraoperatively. During the 4-month postoperative period, a significant clinical improvement and resolution of symptoms were observed. The presented case indicates the need for close and long-term monitoring of patients after EA. In the case of a recurrent reflux oesophagitis in patients after anti-reflux surgery, the possibility of prolonged complications, such as a wrap disruption, herniation or slippage should be taken into consideration.

Impact of decontamination therapy on gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic cell transplantation in children: Decontamination therapy in allo-HCT.

INTRODUCTION: Gut colonization with antibiotic-resistant bacteria (ARB) is associated with a significantly decreased overall survival in adult patients undergoing allo-HCT because of an increased treatment-related mortality. OBJECTIVE: The objective of this multicenter study was the analysis of impact of gut colonization status and the use of antibiotics on development of gastro-intestinal (GI) graft-versus-host disease (GVHD) of allo-HCT in children. METHODS: All consecutive patients who underwent allo-HCT over a period of three years in all pediatric HCT centers in Poland were analyzed for the impact of gut colonization on GI GVHD, with respect to standard of care including prophylaxis of infections and supportive therapy. RESULTS: At the time of allo-HCT, 44.2% of pediatric patients were colonized by ARB. Decontamination therapy with antibiotics was applied in 78% of children. Gut decontamination prophylactic therapy with antibiotics decreased the risk of acute GI GVHD. The use of gentamicin contributed to decreased rate of GVHD, while the use of ciprofloxacin and colistin contributed to increased incidence of GVHD after allo-HCT in children. Sepsis with ARB and non-MFD transplant contributed significantly to worse survival, while neither colonization nor gut decontamination had an impact on overall survival. CONCLUSIONS: Gut decontamination therapy contributed to lower incidence of acute GI GVHD in children undergoing allo-HCT, and the use of specific antibiotics might be responsible for this effect.

Acute Lymphoblastic Leukemia in Children: Better Transplant Outcomes After Total Body Irradiation-based Conditioning.

BACKGROUND/AIM: Comparison of transplant outcomes in long-term follow-up of children after total body irradiation (TBI)- or chemotherapy-based conditioning allogeneic hematopoietic cell transplantation (allo-HCT). PATIENTS AND METHODS: Patients undergoing allo-HCT for Acute lymphoblastic leukemia (ALL) conditioned either with TBI (n=55) or chemotherapy (n=84) were compared. The following transplant outcomes were analyzed: overall survival (OS), event-free survival (EFS), relapse incidence (RI), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS). RESULTS: All analyzed long-term transplant outcomes were significantly better for patients conditioned with TBI at 2 years after transplant. OS at 2 years was 84% after TBI and 60.5% after chemotherapy-conditioning (p=0.005). Risk factor analysis showed that two factors, TBI-based conditioning and transplant in first remission of ALL, significantly improved OS, EFS, GRFS, and decreased RI. CONCLUSION: TBI-based conditioning before allogeneic HCT in children with acute lymphoblastic leukemia provides significantly better transplant outcomes, when compared to chemotherapy-based conditioning.