Alveolar ridge bone changes in patients treated with the split-crest technique with simultaneous implant placement: A retrospective longitudinal observational study.

OBJECTIVES: To investigate long-term alveolar ridge bone changes in patients treated with the split-crest technique (SCT) with simultaneous implant placement. MATERIALS AND METHODS: Alveolar ridge width (ARW) was measured with a caliper immediately before (ARW1) and after SCT (ARW2) with a caliper. Existing CBCT scans taken at least 5 years postoperatively were used to assess the healed ARW (ARWF), buccal bone thickness (BBT), and lingual/palatal bone thickness (L/PBT) at 0, 3, and 5 mm apically from implant platform level (IPL). The distance between IPL and buccal bone crest (IPL-BBC) was also measured. Findings were compared with Wilcoxon and Student's t tests (p < .05). RESULTS: Records of thirty patients with 85 implants were included. Eleven patients (31 implants) presented CBCT scans taken in two separate occasions, resulting in 116 measurements. Tomographic follow-up ranged from 5 to 18 years (11.5 ± 4.18 years). Mean ARW increased from 3.2 ± 0.6 to 6.6 ± 0.48 mm after SCT, but significantly reduced overtime to 4.46 ± 0.83 mm (ARWF) (p < .0001). Mean BBT was 0.5 ± 0.9, 1.3 ± 0.9, and 2.0 ± 1.2 mm, while mean L/PBT was 0.9 ± 0.7, 1.6 ± 0.9, and 2.1 ± 1.0 mm at 0, 3, and 5 mm from IPL, respectively. IPL-BBC distance varied up to 8.7 mm (1.4 ± 2.0 mm), with 56/116 measurements (51/85 implants) showing IPL-BBC = 0 mm. CONCLUSION: Although SCT with simultaneous implant placement can predictably increase ARW postoperatively, ARW tended to significantly reduce over time, due to reductions in BBT and L/PBT, especially coronally. Nonetheless, 60% of the implants still presented some buccal bone at IPL.

Comparison of the efficiency of initial dental alignment with Invisalign® aligners changed every 7 or 14 days in mature adults: Randomized clinical trial.

OBJECTIVE: To compare the anterior crowding correction after sequential use of the first 5 aligners between two aligner exchange protocols (7 and 14 days) in mature adult patients. MATERIALS AND METHODS: Thirty-six patients over 35 years who received orthodontic treatment with Invisalign® were randomly allocated to two different aligner replacement sequence protocols: Group 1: exchange every 7 days (n = 18); and Group 2: exchange every 14 days (n = 18). All patients were scanned with iTero Element 5D® (Align Technology) in two treatment times: at pre-treatment (T1) and after using the first five aligners (T2). Little's Irregularity Index (LII) and arch widths were evaluated with OrthoCAD software. Intra and intergroup comparisons were performed with the dependent and independent t-tests. The results were considered significant for P < .05. RESULTS: Thirty-five patients completed the study. Both groups' maxillary and mandibular Irregularity Indexesi were significantly lower at T2. There was no significant difference in inter-canine, inter-premolar, and intermolar distances. G2 (14 days) presented a greater decrease in mandibular irregularity than G1 (7 days). CONCLUSION: Both exchange protocols (7 and 14 days) effectively correct anterior crowding in the initial phase of orthodontic treatment with aligners in mature adult patients. However, the 14-day exchange protocol provided a greater correction in mandibular anterior crowding in the evaluated period than the 7-day exchange protocol.

Integrated Relaxation Pressure and Its Diagnostic Ability May Vary According to the Conditions Used for HREM Recording.

Integrated Residual Pressure (IRP) measured under conditions alternative to supine single swallows may provide clinically useful information regarding EGJ relaxation. This study aimed to compare IRP values obtained under different situations and explore their potential clinical utility. We analyzed and compared the values of IRP obtained from healthy volunteers and patients with suspected achalasia during supine single swallows (Ssup-IRP), sitting single swallows (Ssit-IRP), supine multiple rapid swallows (Msup-IRP), and sitting multiple rapid swallows (Msit-IRP). We analyzed the HREM recordings of 40 healthy volunteers and 53 patients with suspected achalasia. The four metrics were significantly different from each other in healthy volunteers (Ssup-IRP > Msup-IRP > Ssit-IRP > Msit-IRP) and their corresponding 95th percentiles were substantially distinct (Ssup-IRP: 25.3 mmHg, Ssit-IRP: 20.9 mmHg, Msup-IRP: 15.9 mmHg, and Msit-IRP: 11.9 mm Hg, respectively). Complete agreement among the four metrics in predicting abnormal IRP was found in 39 of the 47 patients with suspected achalasia who completed the protocol. Optimal cutoffs derived from ROC curve analysis demonstrated ≥ 0.95 specificities for detection of impaired EGJ relaxation among patients with suspected achalasia. Among the eight patients with suspected achalasia with normal Ssup-IRP, five demonstrated abnormal Msit-IRP and four abnormal Ssit-IRP. Significant differences of IRP exist depending on the measurement situation, indicating that correct interpretation of IRP values requires specific cutoffs for each situation.The sensitivities of Ssit-IRP and Msit-IRP in detecting defective EGJ relaxation appear to be slightly higher than that of Ssup-IRP.

Anatomical study of first palmar intermetacarpal flap in cadavers and application for congenital first web contracture in a child with Apert's syndrome.

INTRODUCTION: Reconstructing severe first web contractures often involves using either pedicled forearm flaps, which can cause extensive scarring, or free flaps, which can be highly complex. In this study, we present a local palmar hand flap that overcomes both of these challenges. METHODS: Ten fresh upper limbs were examined after arterial injection with colored latex. The study focused on identifying the most distal palmar vascular cutaneous branches suitable for designing an elliptical cutaneous flap over the volar intermetacarpal area. This flap's width was approximately 50% of the width of the thenar eminence. Additionally, we present the case of an 8-year-old child with a type 1 Upton's Apert's hand, which exhibited a severe first web contracture. RESULTS: In seven cadaver hands, one distal cutaneous perforator was found, while in three hands, two perforators were identified. These perforators originated from the thumb radial collateral artery six times, pollex princeps three times, index radial collateral vessels twice, and thumb ulnar collateral vessels twice. The mean perforator diameter was 0.5 mm (ranging from 0.4 to 0.6 mm), and the mean perforator length was 10 mm (ranging from 0.8 to 12 mm). Using this flap bilaterally in our patient resulted in a straightforward procedure that created a broad and functional first web. A total-thickness skin graft was necessary to cover the proximal thenar area, and fortunately, no complications arose. A wide first web with an intermetacarpal angle of 40° ultimately was obtained scoring 8 on the kapandji. CONCLUSIONS: The first palmar intermetacarpal flap presents itself as a reasonable and uncomplicated option for addressing significant moderate-to-severe first web contractures.

The effect of the interproximal contour of single external hexagon implant restorations on the prevalence of peri-implantitis: A retrospective study.

PURPOSE: The objective of this retrospective study was to evaluate the effect of the interproximal contour of single external hexagon implant restorations on the prevalence of peri-implantitis. MATERIAL AND METHODS: Records of 96 patients and 148 external hexagon (EH) implants with time in function ranging from 1 to 17 years were included in the study. The most recent clinical and radiographic data were collected from records and the prevalence of peri-implantitis was defined according to the 2017 World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions. Marginal bone level (MBL), emergence angle (EA), emergence profile (EP), and crown/implant platform horizontal ratio (CIHR) were obtained from periapical radiographs. Dichotomous variables at the patient- and implant level were compared with association tests. Mann-Whitney U-Test was performed to compare continuous quantitative values between the studied groups. Binomial logistic regression was conducted to identify risk indicators associated with the peri-implantitis event at the patient- and implant level, with the significance level set at 5% for all tests. RESULTS: Nineteen patients (19.2%) and 24 implants (16.2%) with a mean time in function of 5.0 ± 4.7 years were classified as having peri-implantitis. No statistically significant differences concerning gender, mean age, implant location in the jaw, or time in function were observed between patients with or without peri-implantitis (p > 0.05). Of 24 implants with peri-implantitis 10 (41.7%) displayed EA ≤ 30° (16.4%) while 14 (58.3%) presented EA > 30° with no statistical difference between the groups (p > 0.05). No statistically significant associations were identified between EA, EP, or CIHR and the prevalence of peri-implantitis. CONCLUSION: The findings seem to indicate that the EA, EP, and CIHR of single restorations over external hexagon implants are not associated with the presence of peri-implantitis. However, prospective studies with larger samples are required to better ascertain such an association in the long term.

Prevalence of Helicobacter pylori genotypes: cagA, vacA (m1), vacA (s1), babA2, dupA, iceA1, oipA and their association with gastrointestinal diseases. A cross-sectional study in Quito-Ecuador.

BACKGROUND: The most prevalent stomach infection in the world is caused by Helicobacter pylori (H. pylori). Several pathogenicity genes, including cagA, vacA, babA2, dupA, iceA, and oipA, are associated with an increased risk of gastrointestinal disease such as peptic ulcer and stomach cancer. This research aims to determine the prevalence of different H. pylori genotypes and correlate their risk in the development of gastrointestinal diseases in the Ecuadorian population. METHODS: A cross-sectional research of 225 patients at the Calderón Hospital in Quito, Ecuador, was conducted. End point PCRs were run to determine the presence of 16S rRNA, cagA, vacA (m1), vacA (s1), babA2, dupA, iceA1, and oipA virulence genes. Chi-square test, odds ratios (OR) and 95% confidence intervals (CI) were utilized for the statistical analysis. RESULTS: H. pylori infection was present in 62.7% of people. Peptic ulcers were seen in 22.2% and malignant lesions in 3.6% of patients. Genes oipA (93.6%), vacA (s1) (70.9%), and babA2 (70.2%) were the most prevalent. cagA/vacA (s1m1) and cagA/oipA (s1m1) combinations were found in 31.2% and 22.7% of the cases, respectively. Acute inflammation has a significant correlation with the genes cagA (OR = 4.96 95% CI: 1.1-22.41), babA2 (OR = 2.78 95% CI: 1.06-7.3), and the cagA/oipA combination (OR = 4.78, 95% CI: 1.06-21.62). Follicular hyperplasia was associated with iceA1 (OR = 3.13; 95% CI: 1.2-8.16), babA2 (OR = 2.56; 95% CI: 1.14-5.77), cagA (OR = 2.19; 95% CI: 1.06-4.52), and the cagA/oipA combination (OR = 2.32, 95% CI: 1.12-4.84). The vacA (m1) and vacA (s1m1) genes were associated with gastric intestinal metaplasia (OR = 2.71 95% CI: 1.17-6.29) (OR = 2.33 95% CI: 1.03-5.24). Finally, we showed that cagA/vacA (s1m1) gene combination increased the risk of duodenal ulcer development (OR = 2.89, 95% CI 1.10-7.58). CONCLUSION: This study makes a significant contribution by offering genotypic information regarding H. pylori infection. The presence of several H. pylori genes was associated with the onset of gastrointestinal illness in the Ecuadorian population.

Four single implant-supported crowns replacing the maxillary incisors: A retrospective report of 10 cases with 2-9 years of follow-up.

OBJECTIVE: This retrospective case series aimed to assess the stability of the papilla around four single crowns supported by narrow-diameter implants replacing all maxillary incisors. Secondary objectives included assessment of marginal bone level stability, incidence of technical and biological complications, and patient satisfaction. MATERIALS AND METHODS: Individuals with four adjacent implants in maxillary incisor sites, placed with a 3 mm inter-implant distance and rehabilitated with single crowns were included. Retrospective data were obtained from photographs and radiographs taken at the delivery of the prosthesis (baseline-T0). Patients were then recalled (≥2 years after T0) for clinical and radiographic examination (follow-up-T1). Photographs were obtained and patient satisfaction was assessed using a visual analogue scale. Papilla height and marginal bone level were compared over time. RESULTS: Data from 10 patients with medium-low smile lines and rehabilitated with 40 implants, in function for 5.4 ± 1.9 years, were analyzed. The papilla height between implants (T0: 2.3 ± 0.9 mm; T1: 2.6 ± 0.7 mm; p = .011) and between tooth and implant (T0: 3.4 ± 0.9 mm; T1: 3.8 ± 0.8 mm; p = .025) increased significantly over the years. The marginal bone level remained stable over time (T0: 0.88 ± 0.57 mm; T1: 0.71 ± 0.67 mm; p = .007). Patients were highly satisfied (97.7 ± 0.3%) with the treatment outcome. CONCLUSION: Within its limitations, this study demonstrated that four single implant-supported crowns placed at maxillary incisor sites may exhibit soft tissue and marginal bone stability over a long period of time. This treatment approach, however, should be restricted to few patients as it requires a proper case selection and skillful execution of all surgical and prosthetic steps.

How to become a pediatric neurosurgeon in Latin America: training opportunities, current status, and future challenges.

PURPOSE: To provide an analysis of pediatric neurosurgery educational opportunities in Latin America in order to characterize and evaluate the strengths, weaknesses, and limitations to assume a career in pediatric neurosurgery. METHODS: An online survey was distributed to pediatric neurosurgeons in Latin America to assess aspects of pediatric neurosurgical education, working conditions, and training opportunities. The survey was open to neurosurgeons that treat pediatric patients, whether or not they had completed fellowship training in pediatrics. A descriptive analysis was done with a subgroup analysis stratified the results among certified pediatric neurosurgeons and non-certified pediatric neurosurgeons. RESULTS: In total, 106 pediatric neurosurgeons completed the survey, of whose the vast majority completed their training in a Latin American pediatric neurosurgery program. A total of 19 accredited academic programs in pediatric neurosurgery were found in Latin America distributed in 6 different countries. On average, the pediatric neurosurgical training in America Latina has a duration of 278 years, ranging from 1 to > 6 years. CONCLUSIONS: This study is the first of its kind to review pediatric neurosurgical training in Latin America, in which both pediatric and general neurosurgeons provide neurosurgical care to children in the continent; however, we found that in the majority of the cases, children are treated by certified pediatric neurosurgeons, of whose the vast majority were trained in Latin American programs. On the other hand, we found areas of improvement in the specialty in the continent, including regulation of training opportunities, increased support for funding, and more opportunities for education among all countries.

Can a new noninvasive method for assessment of intracranial pressure predict intracranial hypertension and prognosis?

PURPOSE: Individuals with TBI are at risk of intracranial hypertension (ICH), and monitoring of intracranial pressure (ICP) is usually indicated. However, despite many new noninvasive devices, none is sufficiently accurate and effective for application in clinical practice, particularly in the management of TBIs. This study aimed to compare the noninvasive Brain4Care system (nICP) with invasive ICP (iICP) curve parameters in their ability to predict ICH and functional prognosis in severe TBI. METHODS: Observational, descriptive-analytical, and prospective study of 22 patients between 2018 and 2021, simultaneously monitored with nICP and iICP. The independent variables evaluated were the presence of ICH and functional prognoses. The dependent variables were the P2/P1 pressure ratio metrics, time to peak (TTP), and TTP × P2/P1. RESULTS: We found a good nonlinear correlation between iICP and nICP waveforms, despite a moderate Pearson's linear correlation. The noninvasive parameters of P2/P1, P2/P1 × TTP, and TTP were not associated with outcomes or ICH. The nICP P2/P1 ratio showed sensitivity/specificity/accuracy (%) of 100/0/56.3, respectively for 1-month outcomes and 77.8/22.2/50 for 6-month outcomes. The nICP TTP ratio had values of 100/0/56.3 for 1-month and 99.9/42.9/72.2 for 6-month outcomes. The nICP P2/P1 × TTP values were 100/0/56.3 for 1-month outcomes and 81.8/28.6/61.1 for 6-month outcomes. CONCLUSION: Brain4Care's noninvasive method showed low specificity and accuracy and cannot be used as the sole means of monitoring ICP in patients with severe TBI. Future studies with a larger sample of patients with P2 > P1 and new nICP curve parameters are warranted.

Infection by Moniliophthora perniciosa reprograms tomato Micro-Tom physiology, establishes a sink, and increases secondary cell wall synthesis.

Witches' broom disease of cacao is caused by the pathogenic fungus Moniliophthora perniciosa. By using tomato (Solanum lycopersicum) cultivar Micro-Tom (MT) as a model system, we investigated the physiological and metabolic consequences of M. perniciosa infection to determine whether symptoms result from sink establishment during infection. Infection of MT by M. perniciosa caused reductions in root biomass and fruit yield, a decrease in leaf gas exchange, and down-regulation of photosynthesis-related genes. The total leaf area and water potential decreased, while ABA levels, water conductance/conductivity, and ABA-related gene expression increased. Genes related to sugar metabolism and those involved in secondary cell wall deposition were up-regulated upon infection, and the concentrations of sugars, fumarate, and amino acids increased. 14C-glucose was mobilized towards infected MT stems, but not in inoculated stems of the MT line overexpressing CYTOKININ OXIDASE-2 (35S::AtCKX2), suggesting a role for cytokinin in establishing a sugar sink. The up-regulation of genes involved in cell wall deposition and phenylpropanoid metabolism in infected MT, but not in 35S::AtCKX2 plants, suggests establishment of a cytokinin-mediated sink that promotes tissue overgrowth with an increase in lignin. Possibly, M. perniciosa could benefit from the accumulation of secondary cell walls during its saprotrophic phase of infection.

Glomus jugulare in a pediatric patient: case report and literature review.

PURPOSE: The jugular and tympanic glomus are rare neoplasms in the general population, being even more uncommon in the pediatric population. There is considerable morbidity associated with both disease and treatment. Treatment is essentially surgical, carried out in recent years in a multidisciplinary manner using preoperative embolization associated with microsurgery and eventually adjuvant radiotherapy. The outcome depends on the location of the lesion and its proximity to noble structures in addition to multidisciplinary monitoring in the postoperative period. METHODS: In this article, a literature review was carried out in the PubMed database, finding reports from 17 patients diagnosed with the disease. Only articles in English were considered. RESULTS: Moreover, we reported a case of a 14-year-old patient diagnosed with jugulotympanic glomus who underwent radical surgical treatment of the lesion. CONCLUSION: This is a rare case of jugulotympanic glomus in a pediatric patient, who underwent surgical treatment associated with multidisciplinary therapy, with a favorable postoperative outcome.

The genome of the zoonotic malaria parasite Plasmodium simium reveals adaptations to host switching.

BACKGROUND: Plasmodium simium, a malaria parasite of non-human primates (NHP), was recently shown to cause zoonotic infections in humans in Brazil. We sequenced the P. simium genome to investigate its evolutionary history and to identify any genetic adaptions that may underlie the ability of this parasite to switch between host species. RESULTS: Phylogenetic analyses based on whole genome sequences of P. simium from humans and NHPs reveals that P. simium is monophyletic within the broader diversity of South American Plasmodium vivax, suggesting P. simium first infected NHPs as a result of a host switch of P. vivax from humans. The P. simium isolates show the closest relationship to Mexican P. vivax isolates. Analysis of erythrocyte invasion genes reveals differences between P. vivax and P. simium, including large deletions in the Duffy-binding protein 1 (DBP1) and reticulocyte-binding protein 2a genes of P. simium. Analysis of P. simium isolated from NHPs and humans revealed a deletion of 38 amino acids in DBP1 present in all human-derived isolates, whereas NHP isolates were multi-allelic. CONCLUSIONS: Analysis of the P. simium genome confirmed a close phylogenetic relationship between P. simium and P. vivax, and suggests a very recent American origin for P. simium. The presence of the DBP1 deletion in all human-derived isolates tested suggests that this deletion, in combination with other genetic changes in P. simium, may facilitate the invasion of human red blood cells and may explain, at least in part, the basis of the recent zoonotic infections.

Bilateral Dacryoadenitis and Central Nervous System Involvement in a Child With Kimura Disease.

Kimura's disease (KD) is a systemic inflammatory condition characterized by lymphadenopathy and subcutaneous nodules in the head and neck region. The lesions have a distinctive histopathological pattern formed by follicular hyperplasia, eosinophilic infiltrates, fibrosis, and vessel proliferation. The disease may occur at all ages but predominates among young males with autoimmune dysfunctions. Visceral and orbital involvement is uncommon. We report a girl with KD who developed bilateral enlargement of the lacrimal glands and a lesion in the left lateral ventricle of the brain indistinguishable from a central nervous system neoplasia. A biopsy of both the lacrimal gland and the lateral ventricle was consistent with KD.

Gingival recession in mandibular anterior teeth in patients with Class II malocclusion treated with elastics and Twin Force appliance.

INTRODUCTION: This study aimed to compare the early results of gingival recession in patients with Class II malocclusion treated with Class II intermaxillary elastics and the Twin Force appliance. METHODS: The sample comprised 55 patients with Class II malocclusion treated without extraction and divided into 2 groups. Group 1 consisted of 23 patients treated with fixed appliances and Class II elastics, with mean initial age of 15.41 ± 5.65 years and a mean treatment time of 3.11 ± 0.91 years. Group 2 consisted of 32 patients treated with fixed appliances and the Twin Force mandibular protraction appliance, with a mean initial age of 18.45 ± 6.63 years and a mean treatment time of 3.17 ± 1.59 years. Dolphin software measured gingival recession in initial and final intraoral photographs. Initial and final lateral cephalograms were used to measure the position of the mandibular incisors. Intragroup and intergroup comparisons were performed by dependent and independent t tests, respectively. RESULTS: In both groups, there was no significant increase in gingival recession with orthodontic treatment, and there was significant protrusion and buccal inclination of the mandibular incisors. When changes with treatment were compared between the groups, there was no statistically significant difference in gingival recession and mandibular incisor position. CONCLUSIONS: There was no significant increase in gingival recession immediately after orthodontic treatment performed with intermaxillary elastics and the Twin Force appliance.

Reversible Bitemporal Hemihypokinetic Pupil Without Hemianopia: A New Chiasmal Sign.

Chiasmal syndromes present mostly with visual problems, such as changes in visual fields, decreased visual acuity, or dyschromatopsia (and classically without pupillary reflex defects). The prototypical bitemporal hemianopia upon visual field testing can easily suggest chiasmal compression due to sellar/suprasellar involvement. However, because of the complexity of the decussation of fibres at the optic chiasm and the presence of anatomical variants, unpredictable visual fields defects can be detected in chiasmal diseases. In some patients, especially in those who have undergone neurosurgical procedures, visual field examination and neuroimaging may not completely reflect the classical pattern of chiasmal visual loss. We describe a novel semiological sign, reporting a patient in which a pupillary bitemporal hemihypokinesia was not accompanied by hemianopia, with the phenomenon being abolished by surgical resection of the causative pituitary macroadenoma. In addition, this finding was an important tool in making the diagnosis.

Personal and Network-Related Factors Associated to Diagnosis Disclosure Reactions for Children and Adolescents Living with HIV.

The process of human immunodeficiency virus (HIV) diagnosis disclosure for vertically infected young people living with HIV has proven decisive for acceptance/adherence to treatment. Herein, we present a cross-sectional study aiming at evaluating how individual and network related variables are associated with reactions to HIV disclosure among them. We used the egocentric approach with a structured questionnaire applied to individuals aged 15-25 years in an HIV referral center in Rio de Janeiro, Brazil. Outcome variable referred to adoption or not of risk behavior after diagnostic disclosure, was classified as "good"/"bad" reactions. Results showed that, of the 80 study participants, 25% reported a "bad reaction" to diagnostic disclosure, an outcome that was more common for patients with at least one friend in their social support network (OR 4.81; 95%CI [1.05-22.07]). In conclusion, a "bad reaction" to HIV serological disclosure may be associated with inadequate structure of the individual's social support network.

RESUMEN: El proceso de divulgación del diagnóstico del virus de inmunodeficiencia humana (VIH) es decisivo para la aceptación/adhesión a tratamiento de los jóvenes infectados verticalmente que viven con VIH. Presentamos un estudio transversal con el objetivo de evaluar cómo variables individuales y de red están asociadas con reacciones a la divulgación del VIH entre ellos. Utilizamos el enfoque egocéntrico por medio de un cuestionario estructurado aplicado a personas de 15-25 años en un Centro de Referencia para VIH en Río de Janeiro, Brasil. La variable de resultado se refiere a la adopción o no de comportamiento de riesgo después de la divulgación del diagnóstico, clasificadas como reacciones "buena"/"mala". Los resultados mostraron que, de los 80 participantes del estudio, el 25% reportó una "mala reacción" a la divulgación diagnóstica. Este resultado fue más común en pacientes con al menos un amigo en su red de apoyo social (OR:4.81; IC95% [1.05-22.07]). Como conclusión, una "mala reacción" a la divulgación serológica del VIH puede estar asociada con una estructura inadecuada de la red de apoyo social del individuo.

Perillyl alcohol for pediatric TP53- and RAS-mutated SHH-medulloblastoma: an in vitro and in vivo translational pre-clinical study.

PURPOSE: Inhalation of perillyl alcohol (POH) recently emerged as an investigational promising antiglioma strategy. However, little attention has been paid to its therapeutic potential for other brain tumors, especially in the pediatric setting. METHODS: The effects of POH were explored in medulloblastoma cell models belonging to the SHH variant with activation of RAS (ONS-76) or with TP53 mutations (DAOY and UW402), by means of proliferation and invasion assays. Interactions with methotrexate, thiotepa, or ionizing radiation were also assessed. Mice bearing subcutaneous tumors were treated with intraperitoneal injections. Alternatively, animals with intracranial tumors were exposed to intranasal POH alone or combined with radiation. Tumor growth was measured by bioluminescence. Analyses of cytotoxicity to the nasal cavity were also performed, and the presence of POH in the brain, lungs, and plasma was surveyed through chromatography/mass spectrometry. RESULTS: POH decreased cell proliferation and colony formation, with conspicuous death, though the invasive capacity was only affected in the NRAS-mutated cell line. Median-drug effect analysis displayed synergistic combinations with methotrexate. Otherwise, POH showed to be a reasonable radiosensitizer. In vivo, intraperitoneal injection significantly decreased tumor volume. However, its inhalation did not affect orthotopic tumors, neither alone or followed by cranial irradiation. Nasal cavity epithelium showed unimportant alterations, though, no traces of POH or its metabolites were detected in tissue samples. CONCLUSION: POH presents robust in vitro antimedulloblastoma effects and sensitizes cell lines to other conventional therapeutics, reducing tumor volume when administered intraperitoneally. Nevertheless, further improvement of delivery devices and/or drug formulations are needed to better characterize its effectiveness through inhalation.

Evaluating H3F3A K27M and G34R/V somatic mutations in a cohort of pediatric brain tumors of different and rare histologies.

PURPOSE: Somatic mutations on H3 histone are currently considered a genetic hallmark for midline pediatric high-grade gliomas (HGGs). Yet, different tumor histologies have been occasionally described to carry these mutations. Since histone modifications can lead to major epigenetic changes with direct impact on prognosis and treatment, we thought to investigate the occurrence of H3F3A K27M and G34R/V mutations in a cohort of pediatric tumors which included HGGs, low-grade gliomas, ependymomas, medulloblastomas, and a series of rare brain tumor lesions of different histologies. METHODS: A total of 82 fresh-frozen pediatric brain tumor samples were evaluated. PCR or RT-PCR followed by Sanger sequencing for the exon 2 of H3F3A (containing both K27 and G34 hotspots) were obtained and aligned to human genome. Loss of trimethylation mark (H3K27me3) in H3F3A/K27M-mutant samples was confirmed by immunohistochemistry. RESULTS: We found H3F3A/K27M mutation in 2 out of 9 cases of HGGs; no H3F3A/K27M mutations were detected in low-grade gliomas (27), ependymomas (n = 10), medulloblastomas (n = 21), or a series of rare pediatric brain tumors which included meningiomas, dysembryoplastic neuroepithelial tumors (DNETs), central nervous system (CNS) germ-cell tumors, choroid plexus tumors, cortical hamartoma, subcortical tubers, and schwannomas (n = 15). H3F3A/G34R/V mutation was not observed in any of the samples. CONCLUSIONS: Our investigation reinforces the low frequency of H3F3A somatic mutations outside the HGG setting. Interestingly, an atypical focal brainstem glioma carrying H3F3A K27M mutation that showed protracted clinical course with late-onset tumor progression was identified.

Efficacy of platelet-rich plasma and plasma for symptomatic treatment of knee osteoarthritis: a double-blinded placebo-controlled randomized clinical trial.

BACKGROUND: Platelet-rich plasma (PRP) has a still conflicting efficacy for knee osteoarthritis (KOA) and might be a minimally invasive and safe treatment alternative. The potential benefit of only plasma (non-enriched) has never been investigated. Our aim was to evaluate the efficacy of intra-articular platelet-rich plasma (PRP) and plasma to improve pain and function in participants with KOA over 24 weeks. METHODS: Randomized, double-blind, placebo-controlled trial with 3 groups (n = 62): PRP (n = 20), plasma (n = 21) and saline (n = 21). Two ultrasound-guided knee injections were performed with a 2-week interval. The primary outcome was visual analog scale 0-10 cm (VAS) for overall pain at week 24, with intermediate assessments at weeks 6 and 12. Main secondary outcomes were: KOOS, OMERACT-OARSI criteria and TUGT. RESULTS: At baseline, 92% of participants were female, with a mean age of 65 years, mean BMI of 28.0 Kg/m2and mean VAS pain of 6.2 cm. Change in pain from baseline at week 24 were -2.9 (SD 2.5), -2.4 (SD 2.5) and -3.5 cm (SD 3.3) for PRP, plasma and saline, respectively (p intergroup = 0.499). There were no differences between the three groups at weeks 6 and 12. Similarly, there were no differences between groups regarding secondary outcomes. The PRP group showed higher frequency of adverse events (65% versus 24% and 33% for plasma and saline, respectively, p = 0.02), mostly mild transitory increase in pain. CONCLUSIONS: PRP and plasma were not superior to placebo for pain and function improvement in KOA over 24 weeks. The PRP group had a higher frequency of mild transitory increase in pain. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03138317 , 03/05/2017.

A Comparative Study of the Effects of Early Versus Late Cranioplasty on Cognitive Function.

Cranioplasty (CP) after decompressive craniectomy (DC) is associated with neurological improvement. We evaluated neurological recovery in patients who underwent late CP (more than 6 months after DC) in comparison with early CP. This prospective study of 51 patients investigated neurological function using the Addenbrooke's Cognitive Examination Revised (ACE-R), Mini-Mental State Examination (MMSE), Barthel Index (BI), and Modified Rankin Scale (mRS) prior to and after CP. Most patients with traumatic brain injury (74%) were young (mean age 33.4 ± 12.2 years) and male (33/51; 66%). There were general improvements in the patients' cognition and functional status, especially in the late-CP group. The ACE-R score increased from the time point before CP to 3 days after CP (51 ± 28.94 versus 53.1 ± 30.39, P = 0.016) and 90 days after CP (51 ± 28.94 versus 58.10 ± 30.43, P = 0.0001). In the late-CP group, increments also occurred from the time point before CP to 90 days after CP in terms of the MMSE score (18.54 ± 1.51 versus 20.34 ± 1.50, P = 0.003), BI score (79.84 ± 4.66 versus 85.62 ± 4.10, P = 0.028), and mRS score (2.07 ± 0.22 versus 1.74 ± 0.20, P = 0.015). CP is able to improve neurological outcomes even more than 6 months after DC.