Acceptability of compounded preparations - A Romanian pediatric hospital perspective.

Compounded medicines are widely used, especially for pediatric patients. The aim of this study was to evaluate children's acceptability of compounded preparations and to provide information regarding compounding practices' characteristics in a Romanian hospital setting. An observational, cross-sectional, and retrospective study was conducted in three Clinical Pediatric Departments (Emergency Clinical Hospital for Children, Cluj-Napoca). The study population comprised patients under 18 years old taking at least one compounded medication. Study data was collected mainly through an interviewer-administered questionnaire and medicine acceptability was assessed based on the children's first reaction to the preparations using a 3-point facial hedonic scale. A total of 162 compounded medications were evaluated. A positive/negative reaction was reported for 20.83%/58.33%, 20.63%/49.21%, and 66.67%/7.41% of oral, oromucosal and cutaneous dosage forms. Although patient disapproval was recorded for various reasons, medication administration was successful in over 75% of cases. Factors such as fewer steps required for intake of a dose, capsule dosage form, no additional food/drink immediately after drug intake, medication perceived as "easy/very easy" to swallow, were correlated with a better acceptability of oral preparations. This study highlights the importance of identifying factors that can improve the acceptability of compounded preparations and, subsequently, treatment outcomes in pediatric patients.

The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets.

Cholangiopathies are defined as focal or extensive damage of the bile ducts. According to the pathogenetic mechanism, it may be immune-mediated or due to genetic, infectious, toxic, vascular, and obstructive causes. Their chronic evolution is characterized by inflammation, obstruction of bile flow, cholangiocyte proliferation, and progression toward fibrosis and cirrhosis. Immune-mediated cholangiopathies comprise primary sclerosing cholangitis (PSC), autoimmune cholangitis and IgG4-associated cholangitis in adults and biliary atresia (BA), neonatal sclerosing cholangitis (NSC) in children. The main purpose of this narrative review was to highlight the similarities and differences among immune-mediated cholangiopathies, especially those frequent in children in which cholangiocyte senescence plays a key role (BA, NSC, and PSC). These three entities have many similarities in terms of clinical and histopathological manifestations, and the distinction between them can be hard to achieve. In BA, bile duct destruction occurs due to aggression of the biliary cells due to viral infections or toxins during the intrauterine period or immediately after birth. The consequence is the activation of the immune system leading to severe inflammation and fibrosis of the extrahepatic biliary tract, lumen stenosis, and impairment of the biliary flow. PSC is characterized by inflammation and fibrosis of intra- and extrahepatic bile ducts, leading to secondary biliary cirrhosis. It is a multifactorial disease that occurs because of genetic predisposition [human leukocyte antigen (HLA) and non-HLA haplotypes], autoimmunity (cellular immune response, autoantibodies, association with inflammatory bowel disease), environmental factors (infections or toxic bile), and host factors (intestinal microbiota). NSC seems to be a distinct subgroup of childhood PSC that appears due to the interaction between genetic predisposition (HLA B8 and DR3) and the disruption of the immune system, validated by elevated IgG levels or specific antibodies [antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA)]. Currently, the exact mechanism of immune cholangiopathy is not fully understood, and further data are required to identify individuals at high risk of developing these conditions. A better understanding of the immune mechanisms and pathophysiology of BA, NSC, and PSC will open new perspectives for future treatments and better methods of preventing severe evolution.

Use of complementary and alternative medicine in children affected by oncologic, neurologic and liver diseases: a narrative review.

Complementary and alternative medicine (CAM) consist of a broad group of restorative resources often linked to existing local cultures and established health care systems and are also increasingly used in children with some serious illnesses. In this narrative review, we examine the epidemiology of the use, efficacy, and safety of complementary and alternative medicine in pediatric oncology, neurology, and hepatology. We searched for relevant articles published in Pubmed evaluating CAM use and its efficacy in safety in children affected by oncologic, neurologic and liver diseases. CAM is used to improve the success of conventional therapies, but also to alleviate the pain, discomfort, and suffering resulting from the diseases and their treatment, which are often associated with a significant burden of adverse effects. CAM use must be evaluated in children with neurological, oncological and liver diseases.

Wolcott-Rallison Syndrome, a Rare Cause of Permanent Diabetes Mellitus in Infants-Case Report.

Wolcott-Rallison syndrome is a rare cause of permanent neonatal diabetes mellitus caused by mutations in the eukaryotic translation initiation factor 2 alpha kinase 3 gene (EIF2AK3). Individuals affected by this disorder have severe hyperglycemia, pancreatic failure, and bone abnormalities and are prone to severe and life-threatening episodes of liver failure. This report illustrates the case of a 2-month-old infant with extreme hyperglycemia and severe diabetic ketoacidosis. Acute management was focused on correcting severe acidosis. Further management aimed to obtain stable blood glucose levels, balancing the patient's need for comfort and lack of distress with the clinicians' need for adequate information regarding the patient's glycemic control. Genetic testing of the patient and his parents confirmed the diagnosis. The follow-up for 18 months after diagnosis is detailed, illustrating both the therapeutic success of subcutaneous insulin therapy and the ongoing complications that patients with Wolcott-Rallison syndrome are subject to.

The Presence of a 'Sentinel' Vessel as an Anatomical Reference during Hamstring Tendon Harvesting-A Prospective Study.

BACKGROUND: The identification of the branch of the inferior medial genicular artery (bIMGA) in anterior cruciate ligament reconstructions (ACLRs) has previously been considered a landmark by some surgeons, but its consistency remains debated. The aim of this investigation was to evaluate the variability in the appearance and location of bIMGA and to assess its validity as a reliable landmark during hamstring tendon harvesting procedures. METHODS: This prospective, single-center study comprised 213 patients who underwent ACLR over a period of two years. The surgical procedures were conducted by the same surgical team, maintaining uniformity in the approach. The study sought correlations between patient demographics, level of activity, and the potential for successful identification of the bIMGA. RESULTS: A statistically significant association between patient activity levels and successful identification of the bIMGA (p = 0.035) was observed. No significant correlations were found concerning patient demographic characteristics. bIMGA demonstrated a substantial degree of anatomical variability, rendering its consistent identification in the surgical field challenging. CONCLUSIONS: Given the observed variability and the associated difficulty in its identification, the use of the bIMGA as a dependable anatomical reference during ACL graft harvesting is not recommended. This study confirms the inconsistency of bIMGA as a traditional landmark, underscoring the need for research aimed at identifying more consistent and reliable anatomical references to enhance the precision of surgical interventions in ACLR.

Detection of Novel Biomarkers in Pediatric Autoimmune Hepatitis by Proteomic Profiling.

Autoimmune hepatitis (AIH) is characterized by immune-mediated hepatocyte injury resulting in the destruction of liver cells, causing inflammation, liver failure, and fibrosis. Pediatric (AIH) is an autoimmune inflammatory disease that usually requires immunosuppression for an extended period. Frequent relapses after treatment discontinuation demonstrate that current therapies do not control intrahepatic immune processes. This study describes targeted proteomic profiling data in patients with AIH and controls. A total of 92 inflammatory and 92 cardiometabolic plasma markers were assessed for (i) pediatric AIH versus controls, (ii) AIH type 1 versus type 2, (iii) AIH and AIH-autoimmune sclerosing cholangitis overlapping syndrome and (iv) correlations with circulating vitamin D levels in AIH. A total of 16 proteins showed a nominally significant differential abundance in pediatric patients with AIH compared to controls. No clustering of AIH subphenotypes based on all protein data was observed, and no significant correlation of vitamin D levels was observed for the identified proteins. The proteins that showed variable expression include CA1, CA3, GAS6, FCGR2A, 4E-BP1 and CCL19, which may serve as potential biomarkers for patients with AIH. CX3CL1, CXCL10, CCL23, CSF1 and CCL19 showed homology to one another and may be coexpressed in AIH. CXCL10 seems to be the central intermediary link for the listed proteins. These proteins were involved in relevant mechanistic pathways for liver diseases and immune processes in AIH pathogenesis. This is the first report on the proteomic profile of pediatric AIH. The identified markers could potentially lead to new diagnostic and therapeutic tools. Nevertheless, considering the complex pathogenesis of AIH, more extensive studies are warranted to replicate and validate the present study's findings.

The Impact of Living Arrangements on the Prevalence of Falls after Total Joint Arthroplasty: A Comparison between Institutionalized and General Geriatric Population.

Due to population aging, there is an increasing need for orthopedic surgery, especially total knee arthroplasty (TKA) and total hip arthroplasty (THA). In geriatric patients, postoperative falls are common events which can compromise the success of these expensive procedures. The aim of our study was to assess the influence of living arrangements on the prevalence of postoperative falls following joint replacement. We included 441 patients after TKA or THA, living in nursing homes, alone or with family. The prevalence of falls in the first 2 years (15.2%) was significantly influenced by living arrangements: patients with TKA or THA living alone had three times higher odds of falling compared to those living with family, and institutionalized patients with THA had four times higher odds of falling compared to those living with family. Of 67 patients who fell, 6 (8.9%) needed reintervention. For TKA patients, the fall rates were not significantly different between institutions and family, indicating the interest of nursing homes in offering proper care. However, for the THA group, the results were poorer, emphasizing the need for improvement in postoperative rehabilitation. Further multi-centric studies are required for generalizing the impact of living arrangements on fall prevalence after joint replacement.

At the Edge of Orthopaedics: Initial Experience with Transarterial Periarticular Embolization for Knee Osteoarthritis in a Romanian Population.

BACKGROUND: Transarterial embolization (TAE) of genicular artery branches is a relatively new technique that has emerged as a promising method for delaying invasive knee surgery in patients suffering from degenerative knee osteoarthritis (OA). In mild to moderate OA, invasive major surgery can be safely postponed, and patients with major risk factors now have an alternative. Our aim was to examine the impact of TAE on clinical outcomes in individuals with degenerative knee OA over a 12-month period. METHODS: A case series of 17 patients diagnosed with knee OA and treated with TAE was included in the study. Every patient was clinically evaluated at different timeframes according to the Western Ontario and McMaster Universities' arthritis index, knee injury, and osteoarthritis outcome scores, and the 36-item short-form survey (WOMAC, KOOS, and SF-36). RESULTS: At the first follow-up (1 month), KOOS and WOMAC improved from 46.6 ± 13.2 (range 27.3-78.2) to 56.5 ± 13.9 (range 32.3-78.4; p = 0.023) and 49.5 ± 13.2 (range 29.3-82.3) to 59.8 ± 12.6 (range 39.3-83.5, p = 0.018), respectively. Physical SF-36 improved significantly from 42.1 ± 7.75 (range 30.3-57.3) to 50.5 ± 9.9 (range 35.6-67.9; p = 0.032). No significant changes in scores were observed at three, six, or twelve months after TAE. CONCLUSIONS: TAE provided early pain reduction and considerable improvement in quality of life without complications for a consecutive sample of Romanian patients with mild to severe knee OA.

The Role of Vitamin D and Vitamin D Binding Protein in Chronic Liver Diseases.

Vitamin D (calciferol) is a fat-soluble vitamin that has a significant role in phospho-calcium metabolism, maintaining normal calcium levels and bone health development. The most important compounds of vitamin D are cholecalciferol (vitamin D3, or VD3) and ergocalciferol (vitamin D2, or VD2). Besides its major role in maintaining an adequate level of calcium and phosphate concentrations, vitamin D is involved in cell growth and differentiation and immune function. Recently, the association between vitamin D deficiency and the progression of fibrosis in chronic liver disease (CLD) was confirmed, given the hepatic activation process and high prevalence of vitamin D deficiency in these diseases. There are reports of vitamin D deficiency in CLD regardless of the etiology (chronic viral hepatitis, alcoholic cirrhosis, non-alcoholic fatty liver disease, primary biliary cirrhosis, or autoimmune hepatitis). Vitamin D binding protein (VDBP) is synthesized by the liver and has the role of binding and transporting vitamin D and its metabolites to the target organs. VDBP also plays an important role in inflammatory response secondary to tissue damage, being involved in the degradation of actin. As intense research during the last decades revealed the possible role of vitamin D in liver diseases, a deeper understanding of the vitamin D, vitamin D receptors (VDRs), and VDBP involvement in liver inflammation and fibrogenesis could represent the basis for the development of new strategies for diagnosis, prognosis, and treatment of liver diseases. This narrative review presents an overview of the evidence of the role of vitamin D and VDBP in CLD, both at the experimental and clinical levels.

Multisystemic Inflammatory Syndrome in Children, A Disease with Too Many Faces: A Single-Center Experience.

BACKGROUND AND AIM: Multisystemic inflammatory syndrome in children (MIS-C) is a rare and severe condition associated with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection in children with onset approximately 4-6 weeks after infection. To date, the precise mechanism that causes MIS-C is not known and there are many questions related to the etiology, risk factors, and evolution of this syndrome. We aimed to describe the clinical manifestations, treatment methods, and disease evolution and analyze the main risk factors for MIS-C in children hospitalized in our clinic. MATERIAL AND METHODS: We performed a retrospective study including children with MIS-C followed-up in the 2nd Pediatric Clinic of the Emergency Clinical Hospital for Children Cluj-Napoca, Romania, for 13 months (November 2020-December 2021). RESULTS: We included in our cohort 34 children (mean age 6.8 ± 4.6 years) who met MIS-C criteria: high and prolonged fever associated with organ dysfunction (heart, lungs, kidneys, brain, skin, eyes, bone marrow or gastrointestinal organs), and autoantibodies and/or polymerase chain reaction positives for SARS-CoV-2. Nineteen patients (55.88%) had a severe form of the disease, with multiorgan failure and shock, and myocardial or respiratory failure. The number of organs affected in the severe forms was significantly higher (more than 6 in 73.70%) than in mild forms (2-3 in 60%). Cardiac dysfunction, hypoalbuminemia, hypertriglyceridemia and hyponatremia were more important in severe forms of MIS-C. These patients required respiratory support, resuscitation with fluid boluses, vasoactive drugs, or aggressive therapy. All patients with mild forms had fully recovered compared to 63.16% in severe forms. The others with severe forms developed long-term complications (dilation of the coronary arteries, premature ventricular contraction, or myocardial fibrosis). Two patients had an extremely severe evolution. One is still waiting for a heart transplant, and the other died (hemophagocytic lymphohistiocytosis syndrome with multiorgan failure). CONCLUSIONS: From mild to severe forms with multiorgan failure, shock, and many other complications, MIS-C represents a difficult challenge for pediatricians, who must be aware of the correct diagnosis and unpredictable, possibly severe evolution.