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Monkeypox (Mpox) is an infectious disease caused by the Mpox virus belonging to the Orthopoxvirus genus in the Poxviridae family and has been declared by the WHO as a global health emergency owing to its rapid spread during 2022 and 2023. All patients diagnosed with Mpox who were confirmed by PCR between July 2022 and April 2023 were included in this study. In total, 405 patients in whom clade 2 was identified were included. Notably, 99% of included patients were men, with 82% of them aged 20–39 years. Furthermore, 71% were men who had sex with men, and 34% were HIV carriers. Regarding the morphology of the lesions, approximately 63% presented with papulonecrotic rash, which sometimes alternated with pustules depending on the stage they were in. All patients presented with systemic symptoms. Five patients required hospital admission, one of whom died, and presented with HIV and severe immunosuppression. Clinical findings suggest that contact during sexual intercourse is the most likely transmission mechanism and genital involvement is the most frequent clinical form. HIV was the primary comorbidity. Genital lesions were common, especially in vulnerable populations such as those who engage in high-risk sexual behaviors.

Purpose: To examine whether image processing of non-mydriatic DRI Triton SS-OCT (Topcon Corporation, Tokyo, Japan) using the red free filter could assess the presence of choroidal nodules and thus include their detection as a diagnostic criterion in neurofibromatosis type 1 (NF1). Material and methods: We included 417 eyes from 210 patients, 377 - from 190 patients diagnosed with NF1 according to the criteria established by the National Institutes of Health Consensus Development Conference (NIH) and 40 from 20 healthy patients as a control group. The mean age was 9.4 years (range 2 years–18 years). All patients had their visual acuity measured by a test according to age, were examined for the presence of lisch nodules and an Optical Coherence Tomography (OCT) of the macular area was performed. All the OCT images were analysed to check if visible nodules could be identified. Results: Ages 14 (95% CI=(9.7,18.3)) and 12 years (95% CI=(9.1,14)) are the cut-off points that best separate those with choroidal nodules with Triton OCT and lisch with slit lamp, respectively, from those without. lisch nodules were detected in 50% of cases of NF1 patients. The presence of choroidal nodules did not present a statistically significant correlation with the occurrence of optic pathway glioma (p = 0.96) nor with the patient's visual worsening (p = 0.072). A statistically significant correlation was observed between the presence of choroidal nodules and the presence of lisch nodules (p

It was studied the effect of two zilpaterol hydrochloride (ZH) brands on carcass and meat quality traits of crossbred Bos indicus young bulls under tropical conditions. The patented ZH formulation (Zilmax®, ZHp) and a generic brand (Zipamix®, ZHg) were added to the feed (6 ppm) for 30 d before slaughter. Animals (n= 288) were randomly assigned to 1 of 3 diets, with 32 animals per pen and 3 replicates, for a total of 96 bulls per treatment: 1) basal diet without ZH (Control), 2) basal diet supplemented with Zipamix® at 6 ppm in the diet, as fed-basis (ZHg), and 3) basal diet supplemented with Zilmax® at the same concentration in the feed (ZHp). Carcass yield traits were significantly improved by ZH supplementation. Carcasses of ZH-treated bulls were 6-9 kg heavier (P=0.0023) and produced about 8-10 kg more of lean tissue (P

Background: The aim of this study was to test the feasibility and utility of developing patient-derived orthotopic xenograft (PDOX) models for patients with malignant peripheral nerve sheath tumors (MPNSTs) to aid therapeutic interventions in real time. Patient & Methods: A sporadic relapsed MPNST developed in a 14-year-old boy was engrafted in mice, generating a PDOX model for use in co-clinical trials after informed consent. SNP-array and exome sequencing was performed on the relapsed tumor. Genomics, drug availability, and published literature guided PDOX treatments. Results: A MPNST PDOX model was generated and expanded. Analysis of the patient’s relapsed tumor revealed mutations in the MAPK1, EED , and CDK2NA/B genes. First, the PDOX model was treated with the same therapeutic regimen as received by the patient (everolimus and trametinib); after observing partial response, tumors were left to regrow. Regrown tumors were treated based on mutations (palbociclib and JQ1), drug availability, and published literature (nab-paclitaxel; bevacizumab; sorafenib plus doxorubicin; and gemcitabine plus docetaxel). The patient had a lung metastatic relapse and was treated according to PDOX results, first with nab-paclitaxel, second with sorafenib plus doxorubicin after progression, although a complete response was not achieved and multiple metastasectomies were performed. The patient is currently disease free 46 months after first relapse. Conclusion: Our results indicate the feasibility of generating MPNST-PDOX and genomic characterization to guide treatment in real time. Although the treatment responses observed in our model did not fully recapitulate the patient’s response, this pilot study identify key aspects to improve our co-clinical testing approach in real time.

Monkeypox (Mpox) is an infectious disease caused by the Mpox virus belonging to the Orthopoxvirus genus in the Poxviridae family and has been declared by the WHO as a global health emergency owing to its rapid spread during 2022 and 2023. All patients diagnosed with Mpox who were confirmed by PCR between July 2022 and April 2023 were included in this study. In total, 405 patients in whom clade 2 was identified were included. Notably, 99% of included patients were men, with 82% of them aged 20–39 years. Furthermore, 71% were men who had sex with men, and 34% were HIV carriers. Regarding the morphology of the lesions, approximately 63% presented with papulonecrotic rash, which sometimes alternated with pustules depending on the stage they were in. All patients presented with systemic symptoms. Five patients required hospital admission, one of whom died, and presented with HIV and severe immunosuppression. Clinical findings suggest that contact during sexual intercourse is the most likely transmission mechanism and genital involvement is the most frequent clinical form. HIV was the primary comorbidity. Genital lesions were common, especially in vulnerable populations such as those who engage in high-risk sexual behaviors. [ABSTRACT FROM AUTHOR]

Background Selumetinib is the first approved treatment for pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN) in the EU and US, as well as in multiple other countries. Evidence for the management of selumetinib-associated adverse events (AEs) is mostly limited to clinical trials and expanded-access programs. We gathered a panel of European healthcare practitioners with clinical experience prescribing selumetinib and/or managing pediatric patients with NF1-PN to provide recommendations on the prevention and management of AEs. Methods A modified Delphi approach was used to develop the recommendations among the group of experts. Initial statements were developed from a literature review of current management recommendations and regulatory reports. The panel refined the statements and rated the extent to which they agreed with them in 2 sessions and a follow-up survey. The panel comprised 2 pediatric neuro-oncologists, 1 pediatric oncologist, 1 pediatrician, 1 neuropediatrician, 1 oncologist, 1 neurologist, 2 psychologists, and 1 dermatologist. Results The experts agreed on the relative frequency and impact of AEs potentially associated with selumetinib. Consensus-level agreement was reached for 36 statements regarding the prevention and management of AEs potentially associated with selumetinib. Experts recommended treatments for AEs based on their experience. Conclusions The development of a variety of consensus statements indicates expert agreement on best practices for the prevention and management of AEs potentially associated with selumetinib in pediatric patients with NF1-PN. These events are generally manageable and should be considered alongside treatment benefit. Information sharing is warranted as further experience is gained. [ABSTRACT FROM AUTHOR]

Summary: The germline TP53 p.R337H mutation is reported as the most common germline TP53 variant. It exists at a remarkably high frequency in the population of southeast Brazil as founder mutation in two distinct haplotypes with the most frequent co-segregating with the p.E134∗ variant of the XAF1 tumor suppressor and an increased cancer risk. Founder mutations demonstrate linkage disequilibrium with neighboring genetic polymorphic markers that can be used to identify the founder variant in different geographic regions and diverse populations. We report here a shared haplotype among Brazilian, Portuguese, and Spanish families and the existence of three additional distinct TP53 p.R337H alleles. Mitochondrial DNA sequencing and Y-STR profiling of Brazilian carriers of the founder TP53 p.R337H allele reveal an excess of Native American haplogroups in maternal lineages and exclusively European haplogroups in paternal lineages, consistent with communities established through male European settlers with extensive intermarriage with Indigenous women. The identification of founder and independent TP53 p.R337H alleles underlines the importance for considering the haplotype as a functional unit and the additive effects of constitutive polymorphisms and associated variants in modifier genes that can influence the cancer phenotype.

Purpose: Pediatric low-grade gliomas (PLGG) have an excellent overall survival, but frequently need non-surgical therapy at diagnosis or after progression when located in unresectable sites such as the optic pathway. Chemotherapy side effects have led to the need for better-tolerated regimens with a sustained response. Bevacizumab, a humanized anti-VEGF monoclonal antibody has been used in monotherapy and/or in combination for these entities. Here we present our experience with its use in PLGG. Methods: The authors performed a retrospective, observational, single-institution study, between 2008 and 2018, to evaluate the safety and efficacy of bevacizumab in progressive PLGG. Results: Twenty-six patients with a median age at diagnosis of 3.32 years old [0.12–14.7] and a median age at treatment of 8.11 years old [0.41–16.82] were included in the study. Nineteen had optic pathway gliomas and chiasmatic-hypothalamic gliomas (73.1%), 9 of them (47.4%) associated with neurofibromatosis type 1 (NF1). Fourteen non-NF1 tumors were molecularly studied, disclosing BRAF-KIAA1549 fusion transcript in 9, and BRAF V600E mutation in 2. Bevacizumab was administered in combination with other agent(s) in 16 of the 35 treatment courses. Responses were assessed at 3, 12 months and at the end of treatment. Progression free survival at 12 and 36 months was 91.4% and 31.4%, respectively, and no severe adverse events were observed. Conclusions: In our series, Bevacizumab in PLGG showed clinical efficacy with a favorable toxicity profile. Larger prospective studies may determine whether the response is conditional upon age, tumor location, and different histological and/or molecular characterization.

Background: Delaying maternity has been subject of controversy, data from the ESHRE, ASRM and the LARA network, show us that the pregnancy rate in people over 40 with IVF cycles are 6-10%, 20% and 15% respectively. Therefore, we decided to make a descriptive study of the main success rates when patients are treated by IVF cycles with their own ovules and to determine the characteristics of this population of advanced maternal age, who decide to undergo highly complex reproductive treatments. Objective: To determine the results of IVF treatments in women over 40 years of age with their own ovules in terms of pregnancy rate, live birth rate and implantation rate. Methodology: Observational, descriptive, retrospective and crosssectional study in which we analyzed the records of patients treated with IVF with own ovules from year 2015 to 2017 at Hospital Angeles del Pedregal in Mexico City, aged 40 years or more, and treated with their own ovules, with complete files, through data collection and conventional non-probabilistic sampling. Results: the overall pregnancy rate was 22%, the live birth rate was 16%, the implantation rate was 22%, achieving 16% through fresh transfer and 6% through devitrification, the total percentage of ectopic, biochemical pregnancies and abortions was 27.5%. Conclusions: The pregnancy rate decreases according to age especially after 39 years, this study represents the general panorama of a very particular population in our country, where the attention of these patients continues to be a challenge due to the low reserve and ovarian response. [ABSTRACT FROM AUTHOR]

NF2-related schwannomatosis (NF2-related SWN) is an autosomal dominant condition caused by loss of function variants in the NF2 gene, which codes for the protein Merlin and is characterized by the development of multiple tumors of the nervous system. The clinical presentation of the disease is variable and related to the type of the inherited germline variant. Here, we tested if phosphorodiamidate morpholino oligomers (PMOs) could be used to correct the splice signaling caused by variants at ±13 within the intron-exon boundary region and showed that the PMOs designed for these variants do not constitute a therapeutic approach. Furthermore, we evaluated the use of PMOs to decrease the severity of the effects of NF2 truncating variants with the aim of generating milder hypomorphic isoforms in vitro through the induction of the in-frame deletion of the exon-carrying variant. We were able to specifically induce the skipping of exons 4, 8, and 11 maintaining the NF2 gene reading frame at cDNA level. Only the skipping of exon 11 produced a hypomorphic Merlin (Merlin-e11), which is able to partially rescue the observed phenotype in primary fibroblast cultures from NF2-related SWN patients, being encouraging for the treatment of patients harboring truncating variants located in exon 11.

Summary: Background: Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder, predisposing development of benign and malignant tumours. Given the oncogenic potential, long-term surveillance is important in patients with NF1. Proposals for NF1 care and its specific manifestations have been developed, but lack integration within routine care. This guideline aims to assimilate available information on NF1 associated tumours (based on evidence and/or expert opinion) to assist healthcare professionals in undertaking tumour surveillance of NF1 individuals. Methods: By comprehensive literature review, performed March 18th 2020, guidelines were developed by a NF1 expert group and patient representatives, conversant with clinical care of the wide NF1 disease spectrum. We used a modified Delphi procedure to overcome issues of variability in recommendations for specific (national) health care settings, and to deal with recommendations based on indirect (scarce) evidence. Findings: We defined proposals for personalised and targeted tumour management in NF1, ensuring appropriate care for those in need, whilst reducing unnecessary intervention. We also incorporated the tumour-related psychosocial and quality of life impact of NF1. Interpretation: The guideline reflects the current care for NF1 in Europe. They are not meant to be prescriptive and may be adjusted to local available resources at the treating centre, both within and outside EU countries. Funding: This guideline has been supported by the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS). ERN GENTURIS is funded by the European Union. DGE is supported by the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007).

Spontaneous bilateral carotid dissection is a rare entity, of unclear etiology, but with clinical relevance, since it can occur in 15-20% of cases of dissection. We present the clinical case of a 54-year-old man, with arterial hypertension as the only vascular risk factor, who developed, in relation to an upper airway infection, a cerebral infarction of the left carotid circulation, secondary to ipsilateral carotid dissection. Two days later contralateral carotid cerebral ischemia was documented, also secondary to carotid dissection. Subsequently a review and discussion of the subject is made, due to the importance of early detection and management. [ABSTRACT FROM AUTHOR]

Abstract Background Li-Fraumeni Syndrome (LFS) is a cancer predisposition syndrome characterized by the early-onset of multiple primary cancers which can occur at different moments (metachronous onset) or, more rarely, coincidentally (synchronous onset). Here we describe a previously unreported patient with presentation of synchronous Wilms tumor and Choroid plexus papilloma, leading to the diagnosis of a Li-Fraumeni Syndrome (LFS). Case presentation A 6-year-old girl without previous complains presented with abdominal pain. Abdominal US and MRI showed a left renal tumor with subcapsular hematoma. Due to mild headaches, the diagnostic workup included a brain MRI that unexpectedly identified a large left parietal lobe tumor. Histopathological analysis determined the diagnosis of classic Wilms tumor and choroid-plexus papilloma (CPP), respectively. Both neoplasms showed intense nuclear p53 immunostaining associated with the pathogenic TP53 mutation c.844C > T (p.Arg282Trp). Our patient and her father shared the same heterozygous germline TP53 mutation, confirming the diagnosis of familiar Li-Fraumeni syndrome in the girl. The treatment was tailored to simultaneous tumor presentations. Conclusions LFS has been associated with Choroid plexus carcinoma (CPC), but rarely with CPP as in our patient. That suggests that it may be advisable to consider the possibility of analyzing TP53 mutation, not only in all patients with CPC, but also in some patients with CPP, especially when histological or clinical evidences point out to perform this study. The dissimilar presentation of LFS among our patient’s father, not having so far any neoplasia diagnosed, while her daughter presented precociously with two simultaneous different tumors, could be related to possible effects of modifier genes on the underlying mutant p53 genotype.

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