Population pharmacokinetics of gentamicin in acute lymphoblastic leukemia pediatric patients compared to non-oncology patients.

Understanding the pharmacokinetics of gentamicin is essential in special populations, such as pediatric patients with acute lymphoblastic leukemia (ALL), in light of previous studies indicating that ALL patients have a lower volume of distribution than non-ALL patients. Furthermore, validation of such results is needed to ensure their clinical application. Accordingly, this single-center, retrospective, cross-sectional study compares the pharmacokinetic parameters of volume of distribution and clearance (Cl) of gentamicin between ALL and non-ALL patients. Inclusion criteria were pediatric patients aged between 1 and 14 years with or without ALL and receiving intravenous gentamicin for treatment courses > 72 h. Patients' characteristics, such as age, sex, height, serum albumin, diagnosis, serum creatinine (Scr) concentration, dosing, and pharmacokinetic information, including peak and trough concentrations, were retrieved. The study scrutinized a total of 115 pediatric patients, comprising toddlers (15.7 %), children (76.5 %), and adolescents (7.8 %). All patients received gentamicin every 8 h, with an average dose of 2.50 (0.64) mg/kg. Patients were divided into two groups based on disease state, with 45.2 % (n = 52) in the non-ALL group and 54.8 % (n = 63) in the ALL group. Both groups had similar characteristics in terms of gender, weight, body surface area, and dose. The only significant covariates identified were weight and creatinine clearance (Clcr) for volume of distribution (Vd). A significant difference was found in Scr, Clcr, and blood urea nitrogen (BUN); however, no significant difference between ALL and non-ALL patients emerged in the volume of distribution or Cl. In conclusion, the study findings indicate that dosing requirements were similar between the two groups. Further prospective studies with larger sample sizes are warranted.

Sorafenib and Piperine co-loaded PLGA nanoparticles: Development, characterization, and anti-cancer activity against hepatocellular carcinoma cell line.

Hepatocellular carcinoma (HCC) exhibits high mortality rates in the advanced stage (>90 %). Sorafenib (SORA) is a targeted therapy approved for the treatment of advanced HCC; however, the reported response rate to such a therapeutic is suboptimal (<3%). Piperine (PIP) is an alkaloid demonstrated to exert a direct tumoricidal activity in HCC and improve the pharmacokinetic profiles of anticancer drugs including SORA. In this study, we developed a strategy to improve efficacy outcomes in HCC using PIP as an add-on treatment to support the first-line therapy SORA using biodegradable Poly (D, L-Lactide-co-glycolide, PLGA) nanoparticles (NPs). SORA and PIP (both exhibit low aqueous solubility) were co-loaded into PLGA NPs (PNPs) and stabilized with various concentrations of polyvinyl alcohol (PVA). The SORA and PIP-loaded PNPs (SP-PNPs) were characterized using Fourier Transform Infrared (FTIR) Spectroscopy, X-ray Powder Diffraction (XRD), Dynamic Light Scattering (DLS), and Scanning Electron Microscopy (SEM), Release of these drugs from SP-PNPs was investigated in vitro at both physiological and acidic pH, and kinetic models were employed to assess the mechanism of drug release. The in vitro efficacy of SP-PNPs against HCC cells (HepG2) was also evaluated. FTIR and XRD analyses revealed that the drugs encapsulated in PNPs were in an amorphous state, with no observed chemical interactions among the drugs or excipients. Assessment of drug release in vitro at pH 5 and 7.4 showed that SORA and PIP loaded in PNPs with 0.5 % PVA were released in a sustained manner, unlike pure drugs, which exhibited relatively fast release. SP-PNPs with 0.5 % PVA were spherical, had an average size of 224 nm, and had a high encapsulation efficiency (SORA âˆ¼ 82 %, PIP âˆ¼ 79 %), as well as superior cytotoxicity compared to SORA monotherapy in vitro. These results suggest that combining PIP with SORA using PNPs may be an effective strategy for the treatment of HCC and may set the stage for a comprehensive in vivo study to evaluate the efficacy and safety of this novel formulation using a murine HCC model.

Synthesis, Characterization, and Toxicity Assessment of Zinc Oxide-Doped Manganese Oxide Nanoparticles in a Macrophage Model.

The doping of engineered nanomaterials (ENMs) is a key tool for manipulating the properties of ENMs (e.g., electromagnetic, optical, etc.) for different therapeutic applications. However, adverse health outcomes and the cellular biointeraction of doped ENMs, compared to undoped counterparts, are not fully understood. Previously, we have shown that doping manganese oxide nanoparticles with ZnO (ZnO-MnO2 NPs) improved their catalytic properties. In this study, we assessed the toxicity of ZnO-MnO2 NPs in Raw 264.7 cells. NPs were prepared via an eco-friendly, co-precipitation method and characterized by several techniques, including transmission and scanning electron microscopy, X-ray diffraction, and Fourier transform infrared. The physicochemical properties of ZnO-MnO2 NPs, including size, morphology, and crystalline structure, were almost identical to MnO2 NPs. However, ZnO-MnO2 NPs showed slightly larger particle aggregates and negative charge in cell culture media. Exposure to ZnO-MnO2 NPs resulted in lower toxicity based on the cell viability and functional assay (phagocytosis) data. Exposure to both NPs resulted in the activation of the cell inflammatory response and the generation of reactive oxygen species (ROS). Despite this, exposure to ZnO-MnO2 NPs was associated with a lower toxicity profile, and it resulted in a higher ROS burst and the activation of the cell antioxidant system, hence indicating that MnO2 NP-induced toxicity is potentially mediated via other ROS-independent pathways. Furthermore, the cellular internalization of ZnO-MnO2 NPs was lower compared to MnO2 NPs, and this could explain the lower extent of toxicity of ZnO-MnO2 NPs and suggests Zn-driven ROS generation. Together, the findings of this report suggest that ZnO (1%) doping impacts cellular biointeraction and the consequent toxicological outcomes of MnO2 NPs in Raw 264.7 cells.

Therapeutic benefits of quercetin in traumatic brain injury model exposed to cigarette smoke.

Scientific evidences reported the deleterious effect of cigarette smoking or passive smoking on brain health particularly cognitive functions, blood-brain barrier (BBB) permeability, up-regulation of inflammatory cascades, and depletion of the antioxidant system. These combined effects become more progressive in the events of stroke, traumatic brain injury (TBI), and many other neurodegenerative diseases. In the current study, we investigated the long-term administered therapeutic potential of quercetin in ameliorating the deleterious neurobiological consequences of chronic tobacco smoke exposure in TBI mice. After exposure to 21 days of cigarette smoke and treatment with 50 mg/kg of quercetin, C57BL/6 mice were challenged for the induction of TBI by the weight drop method. Subsequently, a battery of behavioral tests and immunohistochemical analyses revealed the beneficial effect of quercetin on the locomotive and cognitive function of TBI + smoked group mice (p < 0.05 vs control sham). Immunohistochemistry analysis (Nrf2, HO-1, NFkB, caspase 3) demonstrated a marked protection after 21 days of quercetin treatment in the chronic tobacco smoking group possibly by up-regulation of antioxidant pathways, and decreased apoptosis. In conclusion, our findings support the therapeutic effectiveness of quercetin in partly protecting the central neurological functions that become aberrantly impaired in combined habitual cigarette-smoking individuals impacted with TBI.

Radiolucent lesions that may resemble inflammatory periapical lesions: A review article.

Non-endodontic lesions (NEL) closely resemble lesions of endodontic origin. Its etiology can be odontogenic, non-odontogenic, neoplastic, or anatomic variations that can resemble inflammatory periapical lesions in the periapical area. Inflammatory periapical lesions are caused by pulpal pathoses and require endodontic treatment. Since numerous NEL may resemble inflammatory periapical lesions, they can lead to misdiagnosis and inappropriate management. Thus, a detailed review of the patients' medical and dental histories with clinical examination, including radiographic findings, is essential for the proper assessment of periapical lesions. Numerous cases of misdiagnoses of NEL have been reported in literature. Thus, this review aimed to strengthen the awareness of clinicians on periapical radiolucency, which may resemble inflammatory periapical lesions.

The Exposure to Lead (Pb) Exacerbates Immunological Abnormalities in BTBR T+ Itpr3tf/J Mice through the Regulation of Signaling Pathways Relevant to T Cells.

Autism spectrum disorder (ASD) is a common neurodevelopmental illness characterized by abnormal social interactions, communication difficulties, and repetitive and limited behaviors or interests. The BTBR T+ Itpr3tf/J (BTBR) mice have been used extensively to research the ASD-like phenotype. Lead (Pb) is a hazardous chemical linked to organ damage in the human body. It is regarded as one of the most common metal exposure sources and has been connected to the development of neurological abnormalities. We used flow cytometry to investigate the molecular mechanism behind the effect of Pb exposure on subsets of CD4+ T cells in the spleen expressing IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, and Foxp3. Furthermore, using RT-PCR, we studied the effect of Pb on the expression of numerous genes in brain tissue, including IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, and Foxp3. Pb exposure increased the population of CD4+IFN-γ+, CD4+T-bet+, CD4+STAT1+, CD4+STAT4+, CD4+IL-9+, CD4+IRF4+, CD4+IL-22+, and CD4+AhR+ cells in BTBR mice. In contrast, CD4+IL-10+ and CD4+Foxp3+ cells were downregulated in the spleen cells of Pb-exposed BTBR mice compared to those treated with vehicle. Furthermore, Pb exposure led to a significant increase in IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, and AhR mRNA expression in BTBR mice. In contrast, IL-10 and Foxp3 mRNA expression was significantly lower in those treated with the vehicle. Our data suggest that Pb exposure exacerbates immunological dysfunctions associated with ASD. These data imply that Pb exposure may increase the risk of ASD.

Retracted: Resveratrol Derivative, Trans-3, 5, 4'-Trimethoxystilbene, Prevents the Developing of Atherosclerotic Lesions and Attenuates Cholesterol Accumulation in Macrophage Foam Cells.

Mol. Nutr. Food Res.2020, 64, 1 901 115 https://doi.org/10.1002/mnfr.201901115. The above article, published online on 22 January 2020, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal's Editor-in-Chief, Dr. Julia Reuter, and Wiley-VCH GmbH. Following publication, the journal was contacted by the University of Kansas who indicated that three of the co-authors, Jinke Li, Siying Li and Mohammed M. Almutairi, whose affiliations had been noted at the Department of Pharmacology & Toxicology, University of Kansas, were not affiliated with the university. In addition, the journal was made aware of concerns raised by third parties regarding this article which evidences image duplication between Figures 1, 2, 3, 4, 6, and 7, and Table 1 in this article and two other articles purporting to show different data. The authors were contacted to ask for their explanation of the concerns raised, but no response was received. The retraction has been agreed as the editorial team no longer have confidence in the reported results and conclusions given the significant overlap between the results reported in the Figures and other published articles.

Assessment of 5% Amlexanox, 0.1% Triamcinolone Acetonide and 0.03% Tacrolimus in the Management of Oral Lichen Planus.

Objectives: Compare 5% amlexanox, 0.1% triamcinolone acetonide, and 0.03% tacrolimus in the management of oral lichen planus (OLP). Materials and Methods: A received 0.03% tacrolimus, group B received 0.1% triamcinolone acetonide and group C received topical 5% amlexanox. All patients were evaluated for pain on visual analog scale (VAS) and erosive area on day 1, 7, and 15. Results: There was decrease in visual analogue score (VAS) for pain in all tested group after 15 days. There was significant decrease in erosive area in left and right buccal mucosa in all groups after 15 days for inter and intra group comparison. Conclusion: All the drugs used were effective in management of patients with OLP and thus it can be advised to consider these agents as alternatives.

Gingival Biotypes and its Relation to Biologic Width, Alveolar Bone Thickness, Dehiscence and Fenestration in Mandibular Anterior Region: A CBCT Analysis Study.

Background: Gingival biotype and its relationship to biologic width and alveolar bone thickness may affect surgical periodontal therapy outcomes. Hence, it is vital to assess the gingival biotype prior to any of these treatments for its success. Aim: The study aims to compare the thick and thin gingival biotype in the mandibular anterior region concerning biologic width, buccal bone thickness, prevalence and distribution of dehiscence, and fenestration in lower anterior teeth. Materials and Methods: A total of 30 patients were selected for the study based on the inclusion and exclusion criteria. The Cone Beam Computed Tomography analysis was performed in the mandibular anterior area to assess gingival thickness (biotype), biologic width, buccal bone thickness, dehiscence, and fenestrations. The data were analyzed using SPSS version 26. An independent t-test was used to assess the relationship between the variables. Results: Our study identified an increased biologic width in the thick gingival biotype, a higher frequency of dehiscence in the thin gingival biotype than in the thick biotype, and a greater mean alveolar bone thickness in the thick biotype group. Conclusion: A statistical difference was not observed between the groups; however, the thick biotype showed better results than the thinner biotype for the periodontal parameters examined.

Analysis of the Self-Healing Capability of Thermoplastic Elastomer Capsules in a Polymeric Beam Structure Based on Strain Energy Release Behaviour during Crack Growth.

The objective of this study was to investigate the elastic and plastic responses of 3D-printed thermoplastic elastomer (TPE) beams under various bending loads. The study also aimed to develop a self-healing mechanism using origami TPE capsules embedded within an ABS structure. These cross-shaped capsules have the ability to be either folded or elastically deformed. When a crack occurs in the ABS structure, the strain is released, causing the TPE capsule to unfold along the crack direction, thereby enhancing the crack resistance of the ABS structure. The enhanced ability to resist cracks was confirmed through a delamination test on a double cantilever specimen subjected to quasi-static load conditions. Consistent test outcomes highlighted how the self-healing process influenced the development of structural cracks. These results indicate that the suggested self-healing mechanism has the potential to be a unique addition to current methods, which mostly rely on external healing agents.

Adverse Responses following Exposure to Subtoxic Concentrations of Zinc Oxide and Nickle Oxide Nanoparticles in the Raw 264.7 Cells.

The incorporation of engineered nanomaterials (ENMs) in biomedical and consumer products has been growing, leading to increased human exposure. Previous research was largely focused on studying direct ENM toxicity in unrealistic high-exposure settings. This could result in overlooking potential adverse responses at low and subtoxic exposure levels. This study investigated adverse cellular outcomes to subtoxic concentrations of zinc oxide (ZnONPs) or nickel oxide (NiONPs) nanoparticles in the Raw 264.7 cells, a macrophage-like cell model. Exposure to both nanoparticles resulted in a concentration-dependent reduction of cell viability. A subtoxic concentration of 6.25 µg/mL (i.e., no observed adverse effect level) was used in subsequent experiments. Exposure to both nanoparticles at subtoxic levels induced reactive oxygen species generation. Cellular internalization data demonstrated significant uptake of NiONPs, while there was minimal uptake of ZnONPs, suggesting a membrane-driven interaction. Although subtoxic exposure to both nanoparticles was not associated with cell activation (based on the expression of MHC-II and CD86 surface markers), it resulted in the modulation of the lipopolysaccharide-induced inflammatory response (TNFα and IL6), and cells exposed to ZnONPs had reduced cell phagocytic capacity. Furthermore, subtoxic exposure to the nanoparticles distinctly altered the levels of several cellular metabolites involved in cell bioenergetics. These findings suggest that exposure to ENMs at subtoxic levels may not be devoid of adverse health outcomes. This emphasizes the importance of establishing sensitive endpoints of exposure and toxicity beyond conventional toxicological testing.

Effect of monitoring adherence to regular inhaled corticosteroid (ICS) alone or in combination with a long-acting ß2-agonist (LABA) using electronic methods on asthma outcomes: a narrative systematic review.

OBJECTIVES: To evaluate through a systematic review the effectiveness of electronic methods in monitoring adherence to regular inhaled corticosteroids (ICS) alone or in combination with long-acting ß2-agonists (LABAs) and their effect on clinical outcomes. DESIGN: A narrative systematic review. DATA SOURCES: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Web of Science were searched through up to 10 July 2022. ELIGIBILITY CRITERIA: We included peer-reviewed studies of qualitative and quantitative outcomes that compared the effect of electronic methods to routine non-electronic monitoring intervention or placebo among children and adults with asthma on medication adherence rates to regular ICS alone or in combination with LABA, asthma control and asthma exacerbations. DATA EXTRACTION AND SYNTHESIS: Data extraction was performed according to a predetermined sheet specific to the review objectives. The risk of bias was assessed using the Cochrane Risk of Bias Tool for randomised controlled trials and the Risk of Bias in Systematic Reviews tool for systematic reviews. Meta-analysis was not possible based on the findings of the scoping search; however, a narrative review was performed to allow for the grouping of results based on asthma inhaler adherence rates, asthma control and exacerbations. RESULTS: Six articles comprising 98 studies published from 1998 to 2022 in the USA, Canada and the UK were included. Compared with the control, electronic monitoring devices (EMDs) showed a 23% adherence improvement, mean difference (MD) of 23%, 95% CI 10.84 to 34.16, p=0.0002. Asthmatic children were 1.5 times more likely to be adherent using EMDs compared with non-EMD users (RR=1.5, 95% CI 1.19 to 1.9) (p<0.001). Mobile devices and text message reminders (MHealth) showed a 12% adherence improvement (MD 12%, 95% CI 6.22 to 18.03) (p<0.0001), alongside a small to medium improvement in asthma control (standardised mean difference (SMD) 0.31, 95% CI 0.17 to 0.44), small improvement in asthma-related quality of life (SMD 0.26) (p=0.007) and variable risk reduction in asthma exacerbations for digital health (risk ratio 0.53, 95% CI 0.32 to 0.91) (p=0.02) compared with EMDs, which showed insignificant differences (risk ratio 0.89, 95% CI 0.45 to 1.75) (p=0.72). Technologies combined yielded variable adherence effects, with an SMD for eHealth of 0.41, 95% CI 0.02 to 0.79, and MD for digital health was 14.66% higher than the control, 95% CI 7.74 to 21.57. Heterogeneity between studies was significant (eHealth I2=98%, digital I2=94%). CONCLUSION: Electronic methods improved adherence to inhaled medications in asthma. EMDs appear to be the most effective technology, followed by mHealth. The adherence improvement was associated with a small clinical improvement. There was inconsistent overlapping of terminology describing electronic methods that require standardisation. Data on the cost-effectiveness of electronic devices and their utilisation in severe asthma are lacking and require further research. PROSPERO REGISTRATION NUMBER: CRD42022303069.

Correction: Heterogeneous expression of CFTR in insulin-secreting ß-cells of the normal human islet.

[This corrects the article DOI: 10.1371/journal.pone.0242749.].

Outcomes of Pediatric Traumatic Cardiac Arrest: A 15-year Retrospective Study in a Tertiary Center in Saudi Arabia.

BACKGROUND/OBJECTIVE: Traumatic cardiac arrest (TCA) is the cessation of cardiac pumping activity secondary to blunt or penetrating trauma. The aim of this study is to identify the outcomes of traumatic cardiac arrest in pediatric patients within the local community and report the causes and resuscitation management for the defined cases. METHODS: This was a retrospectively conducted cohort study that took place in King Abdulaziz Medical City (KAMC) and King Abdullah Specialized Children Hospital (KASCH) from 2005 to 2021, Riyadh, Kingdom of Saudi Arabia. The study population involved pediatric patients aged 14 years or less who were admitted to our Emergency Department (ED) and had a traumatic cardiac arrest in the ED. RESULTS: There were 26,510 trauma patients, and only 56 were eligible for inclusion. More than half (60.71%, n= 34) of the patients were males. Patients aged four years or less constituted 51.79% (n= 29) of the included cases. The majority of patients were Saudis (89.29%, n= 50). The majority of the patients had cardiac arrest prior to ED admission (78.57%, n= 44). The majority (89.29%, n= 50) had a GCS of 3 at ED arrival. The most frequently observed first cardiac arrest rhythm was asystole, followed by pulseless electrical activity and ventricular fibrillation, accounting for 74.55%, 23.64%, and 1.82%, respectively. CONCLUSION: Pediatric TCA is high acuity. Children who experience TCA have dreadful outcomes, and survivors can suffer serious neurological impairments. We provided the experience of one of the largest trauma centers in Saudi Arabia to standardize the approach for managing TCA and, hopefully, improve its outcomes.

Effect of Maxillary Expansion on the Maxillary Arch Width in Patients with Bilateral Cleft Palate: A Review.

OBJECTIVES: To perform a comprehensive review of the literature to compare the effects of slow maxillary expansion (SME) and rapid maxillary expansion (RME) on maxillary arch width in patients with bilateral cleft palate. METHODS: The databases include Medline, PubMed, Cochrane (CENTRAL) and (CDSR), OpenGrey, and ClinicalTrials.gov were searched for relevant studies that met the eligibility criteria published before or on 31 October 2022. The search was confined to the English language. The selection of eligible studies and collection of data were performed independently. Risk of bias assessment was conducted using the Cochrane Risk of Bias tool 2.0. RESULTS: Two randomized controlled trials were available based on the search in the published literature. Both studies compared arch width between SME and RME in cleft palate patients and digitals casts and three-dimensional images used for the evaluation. A moderate risk of bias was evident in the available studies. CONCLUSIONS: Both SME and RME can achieve similar amounts of maxillary expansion in patients with bilateral cleft palate.

Cadmium Exposure Is Associated with Behavioral Deficits and Neuroimmune Dysfunction in BTBR T+ Itpr3tf/J Mice.

Autism spectrum disorders (ASD) are neurobehavioral disabilities characterized by impaired social interactions, poor communication skills, and restrictive/repetitive behaviors. Cadmium is a common heavy metal implicated in ASD. In this study, we investigated the effects of Cd exposure on BTBR T+ Itpr3tf/J (BTBR) mice, an ASD model. We looked for changes in repetitive behaviors and sociability through experiments. We also explored the molecular mechanisms underlying the effects of Cd exposure, focusing on proinflammatory cytokines and pathways. Flow cytometry measured IL-17A-, IL-17F-, IL-21-, TNF-α-, STAT3-, and RORγt-expressing CD4+ T cells from the spleens of experimental mice. We then used RT-PCR to analyze IL-17A, IL-17F, IL-21, TNF-α, STAT3, and RORγ mRNA expression in the brain. The results of behavioral experiments showed that Cd exposure significantly increased self-grooming and marble-burying in BTBR mice while decreasing social interactions. Cd exposure also significantly increased the number of CD4+IL-17A+, CD4+IL-17F+, CD4+IL-21+, CD4+TNF-α+, CD4+STAT3+, and CD4+RORγt+ cells, while upregulating the mRNA expression of the six molecules in the brain. Overall, our results suggest that oral exposure to Cd aggravates behavioral and immune abnormalities in an ASD animal model. These findings have important implications for ASD etiology and provide further evidence of heavy metals contributing to neurodevelopmental disorders through proinflammatory effects.

A Systematic Review of Clinical Pharmacokinetics of Inhaled Antiviral.

Background and Objectives: The study of clinical pharmacokinetics of inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy of these drugs and how best to use them in the treatment of respiratory viral infections such as influenza and the current COVID-19 pandemic. The article presents a systematic review of the available pharmacokinetic data of inhaled antivirals in humans, which could be beneficial for clinicians in adjusting doses for diseased populations. Materials and Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted using multiple databases, and studies were screened by two independent reviewers to assess their eligibility. Data were extracted from the eligible studies and assessed for quality using appropriate tools. Results: This systematic review evaluated the pharmacokinetic parameters of inhaled antiviral drugs. The review analyzed 17 studies, which included Zanamivir, Laninamivir, and Ribavirin with 901 participants, and found that the non-compartmental approach was used in most studies for the pharmacokinetic analysis. The outcomes of most studies were to assess clinical pharmacokinetic parameters such as the Cmax, AUC, and t1/2 of inhaled antivirals. Conclusions: Overall, the studies found that the inhaled antiviral drugs were well tolerated and exhibited favorable pharmacokinetic profiles. The review provides valuable information on the use of these drugs for the treatment of influenza and other viral respiratory infections.

Diagnostic Yield of Neuroimaging for Headache in a Pediatric Emergency Department: A Single Tertiary Centre Experience.

OBJECTIVES: This study aimed to examine headache neuroimaging findings among the pediatric population visiting the emergency department in Saudi Arabia. METHODS: This was a cross-sectional retrospective study of pediatric patients who presented to the emergency department with a headache as their primary complaint. Data were extracted from the electronic medical files of the patients at King Abdullah Specialized Children Hospital (KASCH) between 2015 and 2020. The diagnosis of headache was confirmed using a computerized tomography (CT) scan or magnetic resonance imaging (MRI) upon the patients' presentation. RESULTS: A total of 263 patients met the inclusion criteria, and their data were extracted. The CT scans were abnormal in 50% of the patients. The MRI showed abnormal findings for 26% of the patients. CT scans and MRI identified that abnormalities were predominantly among patients with the secondary type of headache. The most common abnormal findings on CT were sinusitis (16%), masses (7%), and hydrocephalus (7%). The most common abnormal findings on MRI were masses (8%), cysts (5%), and hydrocephalus (3%). Of all patients with headaches, 10% had a prior diagnosis of headache, and 12% had a family history of headache. A significantly higher percentage of patients with secondary headache were prescribed NSAID and required admission compared to patients with primary headache (p ≤ 0.05). There was no statistically significant differences in the proportion of patients diagnosed with primary and secondary headache in terms of their neurological examination and headache types (p = 0.43). CONCLUSIONS: Neuroimaging is essential for diagnosing headaches in children. Headaches were associated with sinusitis in children. The secondary type was more likely to have abnormal CT and MRI results. Primary type headaches were more common in those with a family history. CT scans and MRIs are needed when a headache is accompanied by an abnormal clinical evaluation. Neuroimaging and mild CT usage may be explored if there are clinical abnormalities or family history.

Approach to Ankle Instability in Patients With a Negative Ankle MRI: A Case Series.

Objectives Injuries to the ankle ligaments are some of the most common musculoskeletal sports injuries. Ankle magnetic resonance imaging (MRI) is the standard diagnostic procedure in today's practice, but its reliability and validity remain controversial. The aim of this study was to explore the approach for patients with negative ankle MRI who continue to have symptoms of ankle instability despite conservative therapy. Methods A total of eight patients who were 14 years or older with negative ankle MRI who continue to have symptoms of ankle instability despite conservative therapy were admitted to our institution from January 1, 2015 to December 31, 2021. Results Eight patients with a mean age of 36, and a mean body mass index (BMI) of 37.7. All patients presented with ankle pain, locking, and giving way in variable severity. All the patients had a radiograph followed by an ankle MRI, which showed normal alignment of ankle joints without abnormality. Initially, all patients were treated conservatively but did not show any improvement. After that, they underwent an operation of lateral ankle ligament reconstruction by modified Brostrom technique, followed by casting and physiotherapy. The symptoms of ankle instability resolved in all patients. The ankle pain resolved completely in six patients, improved in one patient, and did not improve in one patient.  Conclusion Based on our results, we advocate reconstruction surgery by modified Brostrom technique for ligament repair in patients with clinical evidence of chronic ankle instability who have failed a trial of conservative management, even in the context of a normal ankle MRI.

Chromosome 2 Interstitial Deletion (del(2)(q14.1q22.1) Syndrome With Novel Skeletal and Central Nervous System Features.

In this report, we present the case of a Saudi baby boy with a rare de novo interstitial deletion of chromosome 2q14.1-q22.1. His karyotype was confirmed as 46,XY 1(?)q14.2-1q21.3) but further investigation using chromosomal microarray analysis yielded the deletion breakpoints as 2q14.1q22.1. To date, only 10 cases have been reported within or spanning the deletion of the 2q13-2q22.1 region. In comparison to the established cases, our proband shares similar features, such as bitemporal narrowing, deep vein thrombosis, and horseshoe kidney. However, our proband presented with new features which included congenital knee dislocation, congenital vertical talus, bilateral hip dislocation, and myelomeningocele. Moreover, all the reported cases share GLI2 deletion which may reflect the phenotypic features in patients with the deletion of 2q14.1q22.1.