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BACKGROUND: Multisystem inflammatory disease in children (MIS-C) is a post-infectious condition following coronavirus disease-19 infection. Long-term follow-up data suggests that initial clinical severity does not necessarily correlate with long-term outcomes. The long-term immunological response in children with MIS-C remains poorly understood. We analyzed cytokine profiles at diagnosis and during follow-up, in pediatric patients with MIS-C, exploring correlations among cytokine expressions and standard biochemical and hormonal test results. METHODS: Twenty-five MIS-C patients (mean 9.4 ± 3.9) with complete test results at diagnosis and at 6- and 12-months follow-up were included in the study. Selected cytokines, such as IL-9, eotaxin, IP-10, MIP-1ß, RANTES, MCP-1(MCAF), TNF-α, PDGF-B, IL-4, and MIP-1α, were included in the analysis. RESULTS: IP-10, MCP-1 (MCAF), and MIP-1α levels normalized or nearly normalized at 6-12 months, the remaining cytokines, including IL-9, eotaxin, MIP-1ß, RANTES, TNF-α, PDGF-B, IL-4, remained higher in MIS-C than in controls at our last follow-up time. At 6 months post-diagnosis, a mild negative correlation between triglycerides and HOMA-IR with MCP-1 (MCAF), IL-4, and Eotaxin was noted. At the 12-month follow-up we found a mild positive correlation of cortisol and ACTH levels with PDGF-B, MIP-1α, and TNF-α. Conversely, a negative correlation between these cytokines with fasting glucose and HOMA-IR was observed. CONCLUSIONS: Our study findings highlight a notable cytokine-mediated inflammatory response in pediatric patients with MIS-C, characterized by sustained elevated levels over a 12-month monitoring period compared to the control group. We have identified various interrelationships among different cytokines, as well as correlations between heightened cytokine levels and metabolic and hormonal patterns. The pronounced inflammatory response underscores its involvement in acute organ damage, while its persistence suggests potential implications for long-term metabolic disorders.
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OBJECTIVE: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.
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Malformaciones Vasculares del Sistema Nervioso Central , Embolización Terapéutica , Procedimientos Endovasculares , Humanos , Estudios Retrospectivos , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/cirugía , Embolización Terapéutica/efectos adversos , Procedimientos Endovasculares/efectos adversos , Factores de Riesgo , Resultado del TratamientoRESUMEN
An IFNγ-susceptible mutant of Chlamydia muridarum is attenuated in pathogenicity in the genital tract and was recently licensed as an intracellular Oral vaccine vector or intrOv. Oral delivery of intrOv induces transmucosal protection in the genital tract, but intrOv itself is cleared from the gut (without shedding any infectious particles externally) by IFNγ from group 3-like innate lymphoid cells (ILC3s). We further characterized the intrOv interactions with ILC3s in the current study, since the interactions may impact both the safety and efficacy of intrOv as an oral Chlamydia vaccine. Intracolonic inoculation with intrOv induced IFNγ that in return inhibited intrOv. The intrOv-IFNγ interactions were dependent on RORγt, a signature transcriptional factor of ILC3s. Consistently, the transfer of oral intrOv-induced ILC3s from RORγt-GFP reporter mice to IFNγ-deficient mice rescued the inhibition of intrOv. Thus, IFNγ produced by intrOv-induced ILC3s is likely responsible for inhibiting intrOv, which is further supported by the observation that oral intrOv did induce significant levels of IFNγ-producing LC3s (IFNγ+ILC3s). Interestingly, IL-23 receptor knockout (IL-23R-/-) mice no longer inhibited intrOv, which was accompanied by reduced colonic IFNγ. Transfer of oral intrOv-induced ILC3s rescued the IL-23R-/- mice to inhibit intrOv, validating the dependence of ILC3s on IL-23R signaling for inhibiting intrOv. Clearly, intrOv induces intestinal IFNγ+ILC3s for its own inhibition in the gut, which is facilitated by IL-23R signaling. These findings have provided a mechanism for ensuring the safety of intrOv as an oral Chlamydia vaccine and a platform for investigating how oral intrOv induces transmucosal protection in the genital tract.
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Infecciones por Chlamydia , Chlamydia muridarum , Animales , Ratones , Linfocitos , Inmunidad Innata , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Vacunas Atenuadas , Infecciones por Chlamydia/prevención & control , Interleucina-23RESUMEN
PURPOSE OF REVIEW: The purine nucleotide adenosine triphosphate (ATP) is released into extracellular spaces as extracellular ATP (eATP) as a consequence of cell injury or death and activates the purinergic receptors. Once released, eATP may facilitate T-lymphocyte activation and differentiation. The purpose of this review is to elucidate the role of ATP-mediated signaling in the immunological events related to type 1 diabetes (T1D). RECENT FINDINGS: T lymphocytes mediate immune response during the onset of T1D and promote pancreatic islet or whole pancreas rejection in transplantation. Recent data suggest a potential role for eATP in early steps of T1D onset and of allograft rejection. In different preclinical experimental models and clinical trials, several drugs targeting purinergic signaling have been employed to abrogate lymphocyte activation and differentiation, thus representing an achievable treatment to prevent/revert T1D or to induce long-term islet allograft function. SUMMARY: In preclinical and clinical settings, eATP-signaling inhibition induces immune tolerance in autoimmune disease and in allotransplantation. In this view, the purinergic system may represent a novel therapeutic target for auto- and allo-immunity.
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Enfermedades Autoinmunes , Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Enfermedades Autoinmunes/tratamiento farmacológico , Trasplante Homólogo , Linfocitos T/metabolismo , Adenosina Trifosfato/metabolismoRESUMEN
BACKGROUND: Sterotactic radiosurgery is becoming an integral modality in the management of intracranial meningiomas, both as the primary treatment or as adjuvant therapy. This study analyzes the scholarly impact of the top 100 cited articles on the stereotactic radiosurgical management of intracranial meningiomas. METHODS: A ranked list of the 100 most-cited articles was generated using the Scopus database by searching the keywords 'intracranial meningioma' and 'stereotactic radiosurgery'. All articles were then evaluated on multiple criteria regarding both the publication of the articles (year of publication, journal, country of origin, and authors) as well as their methods and foci (type of study, location of studied meningiomas, and type of radiosurgical modality). Quantitaitve and qualitative analyses were then performed from the collected data. RESULTS: The most frequently cited articles on stereotactic radiosurgical management of intracranial meningiomas were published between 1990 and 2016. The average citation-per-year across all papers in the list was 6.1. The most studied anatomic area of intracranial meningiomas was the skull base, with the cavernous sinus being the most well-studied specific site. The most utilized stereotactic radiosurgical modality was Gamma Knife radiosurgery. The country with the highest number of publications was the United States. Twenty-six percent of the articles were published in the journal Neurosurgery; Lunsford, Kondziolka, Flickinger, Sheehan, and Pollock were respectively the most frequent listed authors among this list. The most active academic institute publishing on this topic was the University of Pittsburgh Medical Center. CONCLUSION: Stereotactic radiosurgery is an integral modality in the management of intracranial meningiomas. This bibliometric analysis sheds the light on the ways in which intracranial meningiomas have been studied in the past two decades in order to identify trends among neurosurgeons and radiation oncologists and to reveal areas of rising and declining focus.
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Neoplasias Meníngeas , Meningioma , Radiocirugia , Humanos , Meningioma/radioterapia , Meningioma/cirugía , Radiocirugia/métodos , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirugía , Procedimientos Neuroquirúrgicos , Bibliometría , Resultado del TratamientoRESUMEN
Coronavirus disease 19 (COVID-19) is clinically less severe in children, even if the wide variety and degree of severity of symptoms reported in children pose a still-unresolved challenge for clinicians. We performed an in-depth analysis of the immunological profiles of 18 hospitalized SARS-CoV-2-infected children, whose results were compared to those obtained from 13 age- and sex-matched healthy controls (HC). The patients were categorized as paucisymptomatic/moderate (55.6%) or severe/critical (44.5%) according to established diagnostic criteria and further stratified into the categories of infants (1-12 months), children (1-12 years), and adolescents (>12 years). We assessed SARS-CoV-2-specific RBD antibodies (Ab), neutralizing antibodies (nAb), and circulating cytokines/chemokines in the plasma, and the SARS-CoV-2-specific immune response was measured in PBMCs by gene expression and secretome analyses. Our results showed peculiar circulating cytokine/chemokine profiles among patients sharing a similar clinical phenotype. A cluster of patients consisting of infants with severe symptoms presented hyperinflammatory profiles, together with extremely polarized antibody profiles. In a second cluster consisting of paucisymptomatic patients, a less pronounced increase in the level of inflammatory cytokines, together with an association between the selected cytokines and humoral responses, was observed. A third cluster, again consisting of paucisymptomatic patients, showed a circulating cytokine/chemokine profile which overlapped with that of the HC. The SARS-CoV-2-stimulated production of pro-inflammatory proteins, T lymphocyte activation, and migration-specific proteins, were significantly increased in SARS-CoV-2-infected children compared to the HC. Our findings suggest that immune response activation in the course of SARS-CoV-2 infection in children is directly correlated with clinical severity and, to a lesser extent, age.
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COVID-19 , Humanos , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Citocinas , QuimiocinasRESUMEN
Bisoprolol and nebivolol are highly selective ß1-adrenoceptor antagonists, with clinical indications in many countries within the management of heart failure with reduced left ventricular ejection fraction (HFrEF), ischaemic heart disease (IHD), and hypertension. Nebivolol has additional vasodilator actions, related to enhanced release of NO in the vascular wall. In principle, this additional mechanism compared with bisoprolol might lead to more potent vasodilatation, which in turn might influence the effectiveness of nebivolol in the management of HFrEF, IHD and hypertension. In this article, we review the therapeutic properties of bisoprolol and nebivolol, as representatives of "second generation" and "third generation" ß-blockers, respectively. Although head-to-head trials are largely lacking, there is no clear indication from published studies of an additional effect of nebivolol on clinical outcomes in patients with HFrEF or the magnitude of reductions of BP in patients with hypertension.
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Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Hipertensión , Isquemia Miocárdica , Antagonistas Adrenérgicos beta/uso terapéutico , Benzopiranos/efectos adversos , Bisoprolol/farmacología , Bisoprolol/uso terapéutico , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/tratamiento farmacológico , Etanolaminas/farmacología , Etanolaminas/uso terapéutico , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Isquemia Miocárdica/tratamiento farmacológico , Nebivolol/efectos adversos , Volumen Sistólico , Vasodilatadores/uso terapéutico , Función Ventricular IzquierdaRESUMEN
To assess the effect of a fermented rice-flour obtained from Lactobacillus paracasei CBA L74 in managing infants with moderate to severe atopic dermatitis. Infants with moderate to severe atopic dermatitis, aged 6-36 months, were randomly assigned to receive once-daily consumption of rice flour containing heat-killed probiotic Lactobacillus paracasei CBA L74 or placebo for 12 weeks as supplementary approach to topical treatment. Primary outcome was SCORAD index change from baseline to 12 weeks; secondary outcomes were gut microbiota composition, as evaluated by the analysis of fecal samples, and serum cytokines at baseline and at the end of the intervention period in both groups, and steroid usage over the treatment period and one month after stopping it. V3-V4 region of the 16S ribosomal RNA gene was sequenced to evaluate changes in the gut microbiota. SCORAD index decreased over the treatment period in both groups. The difference in the SCORAD change was -2.1 (-5.5 to 1.3; p = 0.223) for the experimental vs. the placebo group, not reaching the minimal clinical difference of 8.7 units. The use of topical steroids, measured as finger tips units, decreased from 4 to 16 weeks, in both groups; the reduction was significantly higher in experimental than in placebo group (p value from Wilcoxon rank sum test = 0.031). No significant differences were observed for cytokines levels between groups. The composition of gut microbiota at the phylum and class taxonomic levels resulted very similar, at baseline and after intervention, in both groups. Similarly, no significant differences were observed in the relative abundance of bacterial genera between groups. In conclusion, though the heat-killed Lactobacillus paracaseiwas not proved to be effective in reducing the severity of atopic dermatitis, it showed a steroid sparing effect the value of which needs to be further investigated.
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Dermatitis Atópica/terapia , Harina/microbiología , Lacticaseibacillus paracasei , Oryza , Probióticos/uso terapéutico , Bacterias/genética , Preescolar , Citocinas/sangre , Dermatitis Atópica/sangre , Dermatitis Atópica/microbiología , Método Doble Ciego , Heces/microbiología , Femenino , Fermentación , Microbioma Gastrointestinal/genética , Humanos , Lactante , Masculino , ARN Ribosómico 16S , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: Weight reduction can effectively improve nonalcoholic fatty liver disease (NAFLD), which is a constant companion of severe obesity. This study aimed to determine the effect of one-anastomosis gastric bypass (OAGB) on pathological liver changes in severely obese cases with NAFLD. METHODS: The present prospective research comprised 67 subjects with morbid obesity scheduled for OAGB during the period from February 2015 to August 2018. Clinical, biological, and histologic data were evaluated pre and 15 months postoperatively. RESULTS: Fifteen months after surgery, a considerable reduction was noted in the grades of fat deposition, liver cell ballooning, and lobular inflammatory changes, in addition to the total NAS score. Fifteen months after surgery, nonalcoholic steatohepatitis (NASH) disappeared in 42% of the patients. A significant regression of fibrosis stage occurred after surgery in 79.1% of patients (p < 0.001). After surgery, patients had substantial reductions in aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, HbA1c, total cholesterol, and Low-density lipoprotein (p < 0.001, for all comparisons). Diabetes mellitus, hypertension, and dyslipidemia resolved in 54%, 59%, and 69% of the patients, respectively. CONCLUSION: OAGB resolved NASH from nearly 42% of patients and reduced the histological features of NAFLD 15 months after surgery. Bariatric procedures might be adopted as a therapeutic modality in severely obese cases with NAFLD after the failure of lifestyle modifications.
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Derivación Gástrica , Hígado/patología , Hígado/cirugía , Enfermedad del Hígado Graso no Alcohólico/patología , Adulto , Alanina Transaminasa/metabolismo , Anastomosis Quirúrgica , Aspartato Aminotransferasas/metabolismo , Femenino , Humanos , Cirrosis Hepática/patología , Masculino , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Pérdida de PesoRESUMEN
BACKGROUND: Bariatric procedures are the most effective management for obesity. There is no standard venous thromboembolism (VTE) prophylaxis for both dosing and duration of anticoagulation following laparoscopic sleeve gastrectomy. Our purpose was to assess the optimum regimen for VTE prophylaxis in bariatric procedures and to reduce the incidence of perioperative bleeding. METHODS AND MATERIALS: This is a prospective randomized study which involved 100 morbidly obese patients, subdivided into two groups; group A received postoperative low molecular weight heparin (LMWH) prophylaxis alone starting from day 1 to day 15 in dose 1 mg/kg/day in a maximum dose 120 mg/day, and group B received both pre- and postoperative LMWH; at night of surgery 12 h preoperatively and postoperative starting from day 1 to day 15 with the same dose. All patients underwent mesenteric and bilateral lower limbs duplex 15 days postoperative using Philips iU machine and linear (L9-3), convex (C5-1) and sector (S5-1) probes. RESULTS: Regarding postoperative VTE, we found statistically significant increase in postoperative VTE in patients of group A (four cases) without any case complicated with VTE in patients of group B (P value = 0.041). Regarding postoperative bleeding, we found statistically insignificant percent of cases complicated with postoperative bleeding in group B compared to group A (P value 0.315). CONCLUSION: Preoperative as well as a postoperative prophylactic anticoagulant as LMWH is recommended to prevent perioperative VTE. There was an insignificant increase in postoperative bleeding in patients who received preoperative prophylactic anticoagulants.
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Anticoagulantes/uso terapéutico , Cirugía Bariátrica , Heparina de Bajo-Peso-Molecular/uso terapéutico , Obesidad Mórbida , Tromboembolia Venosa , Adolescente , Adulto , Anticoagulantes/administración & dosificación , Cirugía Bariátrica/efectos adversos , Quimioprevención , Enoxaparina/administración & dosificación , Enoxaparina/uso terapéutico , Femenino , Heparina de Bajo-Peso-Molecular/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Cuidados Posoperatorios , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Cuidados Preoperatorios , Estudios Prospectivos , Tromboembolia Venosa/diagnóstico por imagen , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Adulto JovenRESUMEN
Vehicle-to-vehicle communication is a promising paradigm that enables all vehicles in the traffic road to communicate with each other to enhance traffic performance and increase road safety. Through vehicle-to-vehicle (V2V) communication, vehicles can understand the traffic conditions based on the information sent among vehicles on the road. Due to the potential delay caused by traffic jams, emergency vehicles may not be able to reach their destination in the required time, leading to severe losses. The case is more severe especially in developing countries where no emergency-vehicle-dedicated lanes are allocated. In this study, a new emergency vehicle route-clarifying strategy is proposed. The new clarifying strategy is based on vehicular traffic management in different interference medium scenarios. The proposed model aims, through V2V communication, to find the nearest vehicle with which to communicate. This vehicle plays an important role in reducing the travel time: as the emergency message is received, this vehicle will immediately communicate with all the neighboring vehicles on the road. Based on V2V communications, all the vehicles in the road will clear from the lane in the road for the emergency vehicle can safely reach its destination with the minimum possible travel time. The maximum distance between the emergency vehicle and the nearest vehicle was determined under different channel conditions. The proposed strategy applied an optimization technique to find the varied road traffic parameters. The proposed traffic management strategy was evaluated and examined through different assumptions and several simulation scenarios. The obtained results validated the effectiveness and the accuracy of the proposed model, and also indicated significant improvement in the network's performance in terms of packet delivery ratio (PDR) and average end-to-end delay (E2E).
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Comunicación , Viaje , Simulación por ComputadorRESUMEN
BACKGROUND & AIM: Bariatric surgery is a valid treatment option for persons with non-alcoholic fatty liver disease. This study prospectively examined the impact of laparoscopic sleeve gastrectomy (LSG) on liver histopathology, and blood levels of adiponectin, leptin, resistin, and pre-B cell enhancing factor/Nampt/visfatin. PATIENTS & METHODS: In 81 patients with non-alcoholic fatty liver disease who underwent LSG, paired liver biopsies and blood specimens were obtained before and 18 months after LSG. Differences between preoperative and 18 months postoperative data were tested by paired Student's t-test or Wilcoxon rank test as appropriate. RESULTS: At follow up, there was a significant improvement in biochemical markers for glucose homeostasis, including fasting glucose, HbA1c, insulin levels, and homeostatic model assessment index. Postoperative liver function tests, namely serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase level, showed a significant improvement compared to before weight loss. The number of patients who had definite, borderline, or no non-alcoholic steatohepatitis was 43 (53%), 27 (33%), and 11 (14%), respectively, at baseline, and 9 (11%), 32 (40%), and 40 (49%) at 18-month post-surgery follow up. A significant reduction in steatosis, liver fibrosis, lobular inflammation, and hepatocyte ballooning was observed in the postoperative biopsies (P < 0.001 each). In addition, at the follow-up assessment, there was a significant increase in serum adiponectin levels and significant decline in serum levels of leptin, resisitin, and pre-B cell enhancing factor/Nampt/visfatin. CONCLUSION: Weight loss after sleeve gastrectomy was associated with a significant improvement in several metabolic parameters, liver enzyme levels, liver histopathology, and changes in serum adipokine levels towards antidiabetic and anti-inflammatory profiles.
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Adipoquinas/sangre , Cirugía Bariátrica/métodos , Endoscopía Gastrointestinal/métodos , Gastrectomía/métodos , Laparoscopía/métodos , Hígado/metabolismo , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/cirugía , Pérdida de Peso , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Femenino , Hepatocitos/patología , Humanos , Hipertrofia , Inflamación , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
In recent years, genetic studies have yielded great progress in elucidating causes of male infertility. This investigation aims to identify frequent genetic abnormalities, that is, sex chromosome aneuploidies and Y-chromosome microdeletions among infertile men in Western Saudi Arabia. From a population of infertile patients, 88 male patients with either azoospermia or severe oligozoospermia (sperm concentration <5 million/ml) were selected. In addition to a thorough clinical workup, karyotypes and Y-chromosomal microdeletions were investigated. Among those 88 infertile patients, we detected six patients with Klinefelter syndrome, two with 47 XYY syndrome and two with Y-chromosome microdeletions AZFb,c. While the prevalence of sex chromosome aneuploidies was in the range of globally investigated populations, the microdeletions appeared to be less frequent in Western Saudi Arabia compared to other regions of the world. All genetically abnormal cases showed sperm concentration <1 million/ml, and hence, this appears to be the threshold for warranting genetic investigations in Western Saudi Arabia. Since Klinefelter and 47 XYY syndromes were only discovered late in life, upon an infertility investigation, sex chromosome aneuploidies due to their many-fold comorbidities require earlier medical attention. A neonatal screening programme is suggested for detection of these aneuploidies in Saudi Arabia for the general health benefit of these patients.
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Aneuploidia , Infertilidad Masculina/epidemiología , Síndrome de Klinefelter/epidemiología , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/epidemiología , Adulto , Deleción Cromosómica , Cromosomas Humanos Y/genética , Pruebas Genéticas/métodos , Necesidades y Demandas de Servicios de Salud , Humanos , Incidencia , Infertilidad Masculina/diagnóstico , Infertilidad Masculina/genética , Cariotipificación , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Tamizaje Masivo/métodos , Tamizaje Masivo/organización & administración , Persona de Mediana Edad , Estudios Prospectivos , Arabia Saudita/epidemiología , Aberraciones Cromosómicas Sexuales , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/diagnóstico , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/genética , Recuento de EspermatozoidesRESUMEN
PURPOSE: The selective delivery of chemotherapeutic agent to the affected area is mainly dependent on the mode of drug loading within the delivery system. This study aims to compare the physical method to the chemical method on the efficiency of loading DOX.HCl to GNPs and the specific release of the loaded drug at certain tissue. METHOD: Bifunctional polyethylene glycol with two different functionalities, the alkanethiol and the carboxyl group terminals, was synthesized. Then, DOX·HCl was covalently linked via hydrazone bond, a pH sensitive bond, to the carboxyl functional group and the produced polymer was used to prepare drug functionalized nanoparticles. Another group of GNPs was coated with carboxyl containing polymer; loading the drug into this system by the means of electrostatic adsorption. Finally, the prepared system were characterized with respect to size, shape and drug release in acetate buffer pH 5 and PBS pH 7.4 Also, the effect of DOX.HCl loaded systems on cell viability was assessed using MCF-7 breast cancer cell line. RESULTS: The prepared nanoparticles were spherical in shape, small in size and monodisperse. The release rate of the chemically bound drug in the acidic pH was higher than the electrostatically adsorbed one. Moreover, both systems show little release at pH 7.4. Finally, cytotoxicity profiles against human breast adenocarcinoma cell line (MCF-7) exhibited greater cytotoxicity of the chemically bound drug over the electrostatically adsorbed one. CONCLUSION: Chemical binding of DOX·HCl to the carboxyl group of PEG coating GNPs selectively delivers high amount of drug to tumour-affected tissue which leads to reducing the unwanted effects of the drug in the non-affected ones.
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Antibióticos Antineoplásicos/farmacocinética , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Liberación de Fármacos , Adsorción , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/química , Neoplasias de la Mama/patología , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Oro/química , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Nanopartículas del Metal/química , Polietilenglicoles/química , Electricidad EstáticaRESUMEN
INTRODUCTION: Massive burn patients are at risk of developing intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) as a complication of resuscitation. OBJECTIVE: This study aimed to evaluate the effect of Hydroxyethyl starch (HES) versus 5% albumin solution on intra-abdominal pressure (IAP) in massive burn patients. METHODS: This was a prospective randomized clinical trial carried on at Ain Shams University (ASU) burn unit for 2 years. Where adult patients with burns more than 20% of TBSA were equally randomized into HES group or albumin group. RESULTS: Fifty-two patients were equally randomized into 2 groups. We found no difference in age, sex, weight, type of burn, and TBSA between the two groups. The mean total resuscitation fluid volume in the first 48 h was 213 ml/kg and 206.2 ml/kg for the HES group and the albumin group respectively (p = 0.674). IAP statistically was non-significantly higher in the HES group. We found no statistical difference between the two groups as regards the renal function tests. CONCLUSION: Both HES and 5% albumin solution are effective and safe colloids for burn resuscitation. As regards the IAP, it seems that both 5% albumin and HES have comparable effect regarding IAH in severely burn patients. Both HES and 5% albumin were partially equal in terms of renal involvement and vital data stability.
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Quemaduras , Hipertensión Intraabdominal , Adulto , Humanos , Estudios Prospectivos , Quemaduras/complicaciones , Quemaduras/terapia , Resucitación , Hipertensión Intraabdominal/etiología , Hipertensión Intraabdominal/terapia , Albúminas/uso terapéutico , Almidón , Fluidoterapia/efectos adversosRESUMEN
BACKGROUND: There has been a recent decrease in interventional management of cerebral arteriovenous malformations (AVMs). The objective of our study was to evaluate the changing patterns in management of AVMs in the first year of the COVID-19 pandemic. METHODS: The National Inpatient Sample (NIS) database was used. From 2016 to 2020, patients with an International Classification of Diseases, 10th revision (ICD-10) diagnosis code for a cerebral AVM were included. An intervention was defined as ICD-10 code for surgical, endovascular, or stereotactic radiosurgery treatment. Odds ratios (ORs) were calculated using a logistic regression model with covariates deemed to be clinically relevant. RESULTS: 63 610 patients with AVMs were identified between 2016 and 2020, 14 340 of which were ruptured. In 2020, patients had an OR of 0.69 for intervention of an unruptured AVM (P<0.0001) compared with 2016-19. The rate of intervention for unruptured AVMs decreased to 13.5% in 2020 from 17.6% in 2016-19 (P<0.0001). The rate of AVM rupture in 2020 increased to 23.9% from 22.2% in 2016-19 (P<0.0001). In 2020, patients with ruptured AVMs had an OR for inpatient mortality of 1.72 compared with 2016-19. Linear regression analysis from 2016 to 2020 showed an inverse relationship between intervention rate and rupture rate (slope -0.499, R2=0.88, P=0.019). CONCLUSION: In 2020, the rate of intervention for unruptured cerebral AVMs decreased compared with past years, with an associated increase in the rate of rupture. Patients with ruptured AVMs also had a higher odds of mortality.
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COVID-19 , Malformaciones Arteriovenosas Intracraneales , Radiocirugia , Humanos , Resultado del Tratamiento , Pandemias , Malformaciones Arteriovenosas Intracraneales/epidemiología , Malformaciones Arteriovenosas Intracraneales/terapia , Malformaciones Arteriovenosas Intracraneales/complicaciones , Rotura/cirugía , Estudios RetrospectivosRESUMEN
Background: Keratoconus (KC) is degenerative corneal disorder, with central and paracentral thinning and corneal ectasia. For KC progressive cases, primary treatment included corneal collagen cross linking (CXL) to stabilize coning and intracorneal rings segment (ICRS) to correct visual acuity. Aim: The aim of the study is to assess efficacy and safety of ICRS and CXL on one session (Simultaneous) or two sessions (sequential) with maximum of 1 month apart. Patients and Methods: This Prospective Intervention Comparative research made at Armed forces hospital, Cairo, Egypt from January 2017 to December 2019. Forty patients (60 eyes) with mild to moderate KC were enrolled. Patients sorted into Simultaneous group includes 21 patients (30 eyes) undergo two procedures (ICRS then CXL) at the same session and Sequential group included 19 patients (30 eyes) undergo ICRS then CXL on two sessions with month apart. Patients followed up at end of 1st, 3rd, and 6th months. Assessment included changes in corrected corneal surface irregularities as minimum keratometric 1 (K1), maximum keratometric readings (K2), and mean keratometric (Km) readings. Results: Improvement of K1, K2, and Km in Simulations and Sequential groups achieved at end of 1st-, 3rd-, and 6th-month postoperative versus preoperative. Maximum improvement in Simulations and Sequential groups in K1 achieved at end of 6th and 1st months, in K2 at end of 3rd and 6th months and in Km at end of 1st and 3rd months. Conclusions: Combined ICRS and CXL act safely in one or two sessions and there are no statistically significant variations between results on both methods in keratometric readings.
RESUMEN
BACKGROUND: Preliminary studies show that patients with large vessel occlusion (LVO) acute ischemic strokes have worse outcomes with concurrent COVID-19 infection. We investigated the outcomes for patients with LVO strokes undergoing mechanical thrombectomy (MT) with concurrent COVID-19 infection. METHODS: The National Inpatient Database (NIS) was used for our analysis. Patients in the year 2020 with an ICD-10 diagnosis code for acute ischemic stroke and procedural code for MT were included with and without COVID-19. Odds ratios (OR) were calculated using a logistic regression model with age, sex, stroke location, Elixhauser comorbidity score, and other patient variables deemed clinically relevant as covariates. RESULTS: Patients in the COVID-19 group were younger (64.3±14.4 vs 69.4±14.5 years, P<0.001), had a higher rate of inpatient mortality (22.4% vs 10.1%, P<0.001), and a longer length of stay (10 vs 6 days, P<0.001). Patients with COVID-19 had higher odds of death (OR 2.78, 95% CI 2.11 to 3.65) and lower odds of a routine discharge (OR 0.65, 95% CI 0.48 to 0.89). There was no difference in the odds of subsequent stroke and cerebral hemorrhage, but patients with COVID-19 had statistically significantly higher odds of respiratory failure, pulmonary embolism, deep vein thrombosis, myocardial infarction, acute kidney injury, and sepsis. CONCLUSIONS: Patients with LVOs undergoing MT within the 2020 NIS database had worse outcomes when co-diagnosed with COVID-19, likely due to non-neurological manifestations of COVID-19.
Asunto(s)
Arteriopatías Oclusivas , Isquemia Encefálica , COVID-19 , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Estudios Retrospectivos , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/etiología , Trombectomía/efectos adversos , Resultado del Tratamiento , Accidente Cerebrovascular/etiología , Arteriopatías Oclusivas/etiología , Isquemia Encefálica/terapia , Isquemia Encefálica/etiologíaRESUMEN
BACKGROUND: Transradial access is an important tool for many neuroendovascular procedures. Occlusion of the radial or ulnar artery is not uncommon after transradial or transulnar access and can present a challenge for patients requiring repeat angiography. METHODS: Between March 2022 and June 2023, patients undergoing transradial or transulnar angiography who were found to have a radial artery occlusion or ulnar artery occlusion were identified. Repeat catheterization of the occluded artery was attempted using a 21-gauge single wall puncture needle and a 0.021-inch wire to traverse the occlusion and insert a 23-cm sheath into the brachial artery. RESULTS: A total of 25 patients undergoing 26 angiograms during the study period were found to have a radial artery occlusion or ulnar artery occlusion. Successful repeat catheterization of the occluded artery was achieved in 21 of 26 cases (80.7%). Outer diameter sheath size ranged from 5 Fr (0.0655 inch) to 8 Fr (0.1048 inch). No access complications were encountered. Number of prior angiograms, time since prior angiogram, and prior angiogram procedure time were associated with lower likelihood of successful access. CONCLUSIONS: Transradial or transulnar neuroangiography through an occluded radial or ulnar artery is safe and feasible by traversing the occlusion into the brachial artery with a 23-cm sheath. Repeat catheterization is most successful in patients with an arterial occlusion <6 months old. This technique is important in patients who have limited options for arterial access, avoiding access site complications inherent in transfemoral access, and in patients who specifically require radial or ulnar artery access.
Asunto(s)
Arteriopatías Oclusivas , Arteria Cubital , Humanos , Lactante , Arteria Cubital/diagnóstico por imagen , Arteria Cubital/cirugía , Arteria Braquial/cirugía , Angiografía , Arteria Radial/cirugía , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/cirugía , Arteriopatías Oclusivas/etiología , Angiografía Coronaria/métodosRESUMEN
Chordomas can be treated surgically, with radiotherapy, and more recently, chemotherapy.1,2 A 22-year-old female patient presented with recurrence of a clival chordoma, after subtotal resection at an outside institution 3 months prior. MRI showed a predominantly midline lesion at the craniocervical junction with significant lateral extension eccentric to the left. A 3-staged operation was planned. A redo-endoscopic endonasal transclival transodontoid approach3-5 was used to resect the midline component, followed by an extreme lateral transcondylar transodontoid approach with transposition of the ipsilateral vertebral artery followed by drilling of the ipsilateral occipital condyle and C1 lateral mass to resect the lateral component, followed by occiput to C3 fusion given the induced craniocervical instability. Careful subperiosteal dissection with preservation of the periosteal sheath overlying the vertebral artery was performed. There was no overt evidence of vertebral artery injury intraoperatively or on immediate postoperative imaging. However, 3 weeks later, the patient presented with blood from the oral/nasal cavity. Computed tomography angiography showed an unexpected left vertebral artery pseudoaneurysm. Pseudoaneurysms can develop after microtears in the muscularis layer.6-8 Management is based on size, location, and vertebral artery dominance.9,10 This pseudoaneurysm was coiled. Postcoiling, the patient had left hypoglossal palsy. We demonstrate the step-by-step technique of an extreme lateral transcondylar transodontoid approach for a clival chordoma and the unfortunate complication of a vertebral artery pseudoaneurysm with discussion of its etiology and management options for this potentially devastating complication. The patient consented to the procedure/publication. Institutional Review Board approval not obtained as the patient was deidentified, and no additional risk is posed by the publication of this video.