Prenatal manifestation and management of a mother and child affected by spondyloperipheral dysplasia with a C-propeptide mutation in COL2A1: case report

It is not unusual for patients with "rare" conditions, such as skeletal dysplasias, to remain undiagnosed until adulthood. In such cases, a pregnancy may unexpectedly reveal hidden problems and special needs. A 28 year old primigravida was referred to us at 17 weeks for counselling with an undiagnosed skeletal dysplasia with specific skeletal anomalies suggesting the collagen 2 disorder, spondyloperipheral dysplasia (SPD; MIM 156550)

Isolation and molecular characterisation of Halicephalobus gingivalis in the brain of a horse in Piedmont, Italy

Background: A fatal case of meningoencephalitis was reported in a 13-year-old Koninklijk Warmbloed Paard Nederland stallion, suspected of West Nile virus (WNV) infection, in the Piedmont region of Italy. Clinical signs included right head tilt and circling, depression alternated with excitability, fever and lateral strabismus. Combined treatment consisting of dimethylsulfoxide, dexamethasone, sulphonamides and sedative was administered, but because of the poor conditions the horse was euthanatized and submitted for necropsy. Results: At post-mortem examination no skin lesions were observed, all organs appeared normal on gross evaluation and only head and blood samples were further investigated. Neuropathological findings consisted of granulomatous meningoencephalitis and larvae and adult females of Halicephalobus gingivalis were isolated and identified from the digested brain. Frozen brain was submitted to PCR amplification and 220 bp multiple sequence alignment was analysed by Bayesian phylogenetic analysis. Conclusions: Phylogenetic inference revealed that the isolate belongs to H. gingivalis Lineage 3. WN surveillance can help to deepen our knowledge of horse neurological disorders investigating their causes and incidence. Moreover, it can help to understand the geographic distribution of the H. gingivalis, to unravel epidemiological information, and to estimate risk for humans

Persistent immune stimulation exacerbates genetically driven myeloproliferative disorders via stromal remodeling

Systemic immune stimulation has been associated with increased risk of myeloid malignancies, but the pathogenic link is unknown. We demonstrate in animal models that experimental systemic immune activation alters the bone marrow stromal microenvironment, disarranging extracellular matrix (ECM) microarchitecture, with downregulation of secreted protein acidic and rich in cysteine (SPARC) and collagen-I and induction of complement activation. These changes were accompanied by a decrease in Treg frequency and by an increase in activated effector T cells. Under these conditions, hematopoietic precursors harboring nucleophosmin-1 (NPM1) mutation generated myeloid cells unfit for normal hematopoiesis but prone to immunogenic death, leading to neutrophil extracellular trap (NET) formation. NET fostered the progression of the indolent NPM1-driven myeloproliferation toward an exacerbated and proliferative dysplastic phenotype. Enrichment in NET structures was found in the bone marrow of patients with autoimmune disorders and in NPM1-mutated acute myelogenous leukemia (AML) patients. Genes involved in NET formation in the animal model were used to design a NET-related inflammatory gene signature for human myeloid malignancies. This signature identified two AML subsets with different genetic complexity and different enrichment in NPM1 mutation and predicted the response to immunomodulatory drugs. Our results indicate that stromal/ECM changes and priming of bone marrow NETosis by systemic inflammatory conditions can complement genetic and epigenetic events towards the development and progression of myeloid malignancy

Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease

: Evidence that Huntington's disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing ("early treatment") or reversing ("late treatment") HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally. We show that one cycle of treatment with hybrid-g7-NPs-chol, administered in the presymptomatic ("early treatment") or symptomatic ("late treatment") stages is sufficient to normalize cognitive defects up to 5 months, as well as to improve other behavioral and neuropathological parameters. A multiple cycle treatment combining both early and late treatments ("2 cycle treatment") lasting 6 months generates therapeutic effects for more than 11 months, without severe adverse reactions. Sustained cholesterol delivery to the brain of zQ175DN mice also reduces mutant Huntingtin aggregates in both the striatum and cortex and completely normalizes synaptic communication in the striatal medium spiny neurons compared to saline-treated HD mice. Furthermore, through a meta-analysis of published and current data, we demonstrated the power of hybrid-g7-NPs-chol and other strategies able to increase brain cholesterol biosynthesis, to reverse cognitive decline and counteract the formation of mutant Huntingtin aggregates. These results demonstrate that cholesterol delivery via brain-permeable NPs is a therapeutic option to sustainably reverse HD-related behavioral decline and neuropathological signs over time, highlighting the therapeutic potential of cholesterol-based strategies in HD patients. DATA AVAILABILITY: This study does not include data deposited in public repositories. Data are available on request to the corresponding authors

Clinical evaluation of an evidence-based method based on food characteristics to adjust pancreatic enzyme supplements dose in cystic fibrosis

[EN] Background: Patients with cystic fibrosis (CF) and pancreatic insufficiency need pancreatic enzyme replacement therapy (PERT) for dietary lipids digestion. There is limited evidence for recommending the adequate PERT dose for every meal, and controlling steatorrhea remains a challenge. This study aimed to evaluate a new PERT dosing method supported by a self-management mobile-app. Methods: Children with CF recruited from 6 European centres were instructed to use the app, including an algorithm for optimal PERT dosing based on in vitro digestion studies for every type of food. At base-line, a 24h self-selected diet was registered in the app, and usual PERT doses were taken by the patient. After 1 month, the same diet was followed, but PERT doses were indicated by the app. Change in faecal fat and coefficient of fat absorption (CFA) were determined. Results: 58 patients (median age 8.1 years) participated. Baseline fat absorption was high: median CFA 96.9%, median 2.4g faecal fat). After intervention CFA did not significantly change, but range of PERT doses was reduced: interquartile ranges narrowing from 1447-3070 at baseline to 1783-2495 LU/g fat when using the app. Patients with a low baseline fat absorption (CFA<90%, n= 12) experienced significant improvement in CFA after adhering to the recommended PERT dose (from 86.3 to 94.0%, p=0.031). Conclusion: the use of a novel evidence-based PERT dosing method, based on in vitro fat digestion studies incorporating food characteristics, was effective in increasing CFA in patients with poor baseline fat absorption and could safely be implemented in clinical practice.We acknowledge the support of the MyCyFAPP Project consortium. We especially thank the participation and the effort of the patients involved in the study and their families. This work was fully funded by the European Union and the Horizon 2020 Research and Innovation Framework Programme (PHC-26-2014 call Self management of health and disease: citizen engagement and mHealth) under grant number 643806.Calvo-Lerma, J.; Boon, M.; Colombo, C.; De Koning, B.; Asseiceira, I.; Garriga, M.; Roca, M.... (2021). Clinical evaluation of an evidence-based method based on food characteristics to adjust pancreatic enzyme supplements dose in cystic fibrosis. Journal of Cystic Fibrosis. 20(5):e33-e39. https://doi.org/10.1016/j.jcf.2020.11.016Se33e3920

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy)

Objective To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the frst pandemic wave, Lombardia. Methods Adult patients admitted to 20 Neurological Units between 1/3–30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). Results Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. Conclusions We detected an increased incidence of GBS in COVID-19 patients which can refect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Evaluation of parasite contamination on toothbrushes in children in Southeastern Brazil.

Introduction: The toothbrush is an important object for the hygiene of the oral cavity and an effective mechanism to remove the oral waste. Objective: To evaluate the perception of care, storage and parasitic contamination of toothbrushes in children with special health care needs (CSHCN) and children without special health care needs (CWSHCN) in Southern of Minas Gerais State. Material and Methods: This is an observational cross-sectional non-randomized study. The population consisted in 54 children, with age between 7 and 14 years. The questionnaire was distributed to patients to evaluate the perception of care and storage of children’s toothbrushes. Investigation of toothbrushes contamination was performed by parasitological examination and real-time polymerase chain reactions. Results: Regarding the procedures performed after brushing, 50.0% of children with special health care needs (CSHCN) and 56.3% of children without special health care needs (CWSHCN) report washing their brush bristles with water (p &lt;0.001). Both groups did not use an antiseptic solution on toothbrushes. 73.3% of (CSHCN) and 58.7% of (CWSHCN) answered that they use some protection (brush holder and bathroom cabinet) to avoid exposure of brushes to the environment (p &lt;0.001). Conclusion: The children investigated by the study presented good conditions of care and storage of their toothbrushes. No contamination by pathogenic parasites was found during the study period.Introducción: El cepillo de dientes es un objeto importante para la higiene de la cavidad bucal y un mecanismo eficaz para eliminar los residuos bucales. Objetivo: Evaluar la percepción del cuidado, almacenamiento y contaminación parasitaria de los cepillos dentales en niños con necesidades especiales de salud (CSHCN) y niños sin necesidades especiales de salud (CWSHCN) en el sur del estado de Minas Gerais. Material y Métodos: Se trata de un estudio observacional transversal no aleatorio. La población consistió en 54 niños, con edad entre 7 y 14 años. El cuestionario fue distribuido a los pacientes para evaluar la percepción del cuidado y almacenamiento de los cepillos dentales de los niños. La investigación de la contaminación de los cepillos dentales se realizó mediante un examen parasitológico y reacciones en cadena de la polimerasa en tiempo real. Resultados: En cuanto a los procedimientos realizados tras el cepillado, el 50,0% de los niños con necesidades especiales de atención sanitaria (NCNEAS) y el 56,3% de los niños sin necesidades especiales de atención sanitaria (NSNEAS) refieren lavar las cerdas del cepillo con agua (p &lt;0,001). Ambos grupos no utilizaron una solución antiséptica en los cepillos de dientes. El 73,3% de los (NCNEAS) y el 58,7% de los (NSNEAS) contestaron que utilizan alguna protección (portacepillos y mueble de baño) para evitar la exposición de los cepillos al medio ambiente (p &lt;0,001). Conclusiones: Los niños investigados por el estudio presentaron buenas condiciones de cuidado y almacenamiento de sus cepillos dentales. No se encontró contaminación por parásitos patógenos durante el período de estudio