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OBJECTIVE: Posterior fossa or midline tumors are often associated with hydrocephalus and primary tumor removal with or without perioperative placement of an external ventricular drain (EVD) is commonly accepted as first-line treatment. Shunting prior to posterior fossa surgery (PFS) is mostly reserved for symptomatic cases or special circumstances. There are limited data regarding the anticipated risk for symptomatic pneumocephalus and the perioperative management using the semi-sitting position (SSP) in such a scenario. Here, we therefore assessed the safety of performing PFS in a consecutive series of patients over a period of 15 years to allow the elaboration of recommendations for perioperative management. METHODS: According to specific inclusion and exclusion criteria a total of 13 patients who underwent 17 operations was identified. Supratentorial pneumocephalus was evaluated with semiautomatic-volumetric segmentation. The volume of pneumocephalus was evaluated according to age and ventricular size. RESULTS: Ten of the 13 patients had a programmable valve (preoperative valve setting range 6-14 cmH20; mean 7.5 cmH20) while 3 patients had non programmable valves. A variable amount of supratentorial air collection was evident in all patients postoperatively (range 3.2-331 ml; mean 122.32 ml). Positive predictors for the volume of postoperative pneumocephalus were higher age and a preoperative Evans ratio > 0.3. In our series, we encountered no cases of tension pneumocephalus necessitating an air replacement procedure as well as no obstruction, disconnection, infection or hardware malfunction of the shunt system. CONCLUSIONS: Our findings indicate that a CSF shunt in situ is not a contraindication for performing PFS in the semi-sitting position and it does not increase the pre-existing risk for postoperative tension pneumocephalus. In cases of primary shunting for hydrocephalus associated with posterior fossa tumors a programmable valve set at a medium opening pressure with a gravitational device is a valid option when PFS in the semi-sitting position is opted. In patients with an indwelling shunt diversion system special caution is indicated in order to prevent and detect overdrainage especially in not adjustable valves or shunts without antisiphon devices.
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Hidrocefalia , Neoplasias Infratentoriais , Pneumocefalia , Humanos , Postura Sentada , Pneumocefalia/diagnóstico por imagem , Pneumocefalia/etiologia , Pneumocefalia/prevenção & controle , Procedimentos Neurocirúrgicos/métodos , Neoplasias Infratentoriais/cirurgia , Hidrocefalia/cirurgia , Hidrocefalia/complicações , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/diagnóstico , Derivação Ventriculoperitoneal/efeitos adversosRESUMO
OBJECTIVE: IgG4-related hypertrophic pachymeningitis is a rare fibroinflammatory disorder that may cause localized or diffused thickening of the dura mater. Misinterpretations of the clinical and imaging findings are common. Clinical manifestations depend on the location of the inflammatory lesion and on compression of neural structures leading to functional deficits. A dural biopsy is commonly needed for a definitive diagnosis. Immunomodulatory therapy is considered the therapy of choice. METHODS: Four patients with IgG4-related hypertrophic pachymeningitis were identified over a 5-year period. Patient-related characteristics including age, preoperative workup, signs and symptoms of patients, and diagnostic procedures were evaluated. Furthermore, the surgical treatment and 5-year follow-up outcomes were analyzed. RESULTS: There were two adults and two adolescents (mean age 32 years; range 15 to 67 years). Two patients were male, and two were female. No history of disease was known in any of the patients. Clinical symptoms were epilepsy (n = 2), ataxia and nausea (n = 1), and facial nerve palsy (n = 1). MR imaging studies showed contrast enhancing lesions in the temporal region in two patients, and in the cerebellar region in the other two patients. Subtotal resection was performed in two instances and a biopsy via a suboccipital retrosigmoid approach was obtained in the other two patients. Histochemical and immunohistochemical investigations revealed an IgG 4 disease in all of these patients. Immunomodulatorry therapy led to clinical stability during follow-up of 5 years in all four cases. CONCLUSION: The diagnosis of IgG4-related hypertrophic pachymeningitis is challenging, but is of great relevance as treatment differs significantly from other forms of pachymeningitis and a specific therapeutic approach may avoid long-term neurological complications. Our series contributes to a better clinical characterization of this rare disease.
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Meningite , Neoplasias , Adolescente , Adulto , Dura-Máter/diagnóstico por imagem , Dura-Máter/patologia , Dura-Máter/cirurgia , Feminino , Humanos , Hipertrofia , Imunoglobulina G/uso terapêutico , Imageamento por Ressonância Magnética/efeitos adversos , Masculino , Meningite/diagnóstico , Meningite/etiologia , Neoplasias/complicaçõesRESUMO
Rosette-forming glioneuronal tumor (RGNT) is a rare tumor entity which has been reported mainly occurring in the fourth ventricle. It has been described as a benign lesion with limited extension into surrounding structures, including the cerebellar vermis, midbrain, and cerebral aqueduct. More recently, few cases involving also other midline structures have been documented as well. Here, we report about diagnosis and treatment of RGNT in the septum pellucidum in a pediatric patient which has not been described previously. A 7-year-old boy had a 3-week history of headache. Magnetic resonance imaging showed a solid mass in the septum pellucidum accompanied by hydrocephalus. The tumor was resected via a transcortical approach. Histological examination revealed the typical findings of a RGNT. At 2-year follow-up, there was no tumor recurrence, and clinical outcome was unremarkable. RGNT has to be considered in the differential diagnosis of pediatric midline tumors also outside of the fourth ventricle. Surgical resection is the first-line therapy which may result in beneficial outcome in the long term. The role of adjuvant therapy needs further definition since due to the rarity of this tumor entity, available data is very limited.
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Neoplasias do Ventrículo Cerebral , Glioma , Neoplasias do Ventrículo Cerebral/diagnóstico por imagem , Neoplasias do Ventrículo Cerebral/cirurgia , Criança , Quarto Ventrículo , Glioma/diagnóstico por imagem , Glioma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia , Septo Pelúcido/diagnóstico por imagem , Septo Pelúcido/cirurgiaRESUMO
BACKGROUND: Various synthetic materials are used in neurosurgery and left in place intentionally during surgery for several purposes such as hemostasis, dural closure, or cranioplasty. Although leaving such substances in surgical sites is considered safe, in general, foreign body granuloma may occur months or years after intracranial surgery. Thus, far relatively little is known about treatment and outcome of such lesions. METHODS: A systematic review of 3466 histopathological examinations after cranial surgeries achieved over a 13-year period was performed. After excluding patients with Teflon granulomas or infection, a total of 12 patients with foreign body granulomas induced by synthetic material used in a prior surgery were identified. Patient records, imaging studies, and histopathological data were analyzed. Furthermore, postoperative outcome was assessed. RESULTS: Mean age at the second surgery was 51 years (range, 11-68 years). The median time between the primary and the secondary surgery was 13 months (range, 1-545 months). Eight patients (75%) presented with signs and symptoms related to the foreign body granulomas. Total resection of the foreign body granulomas was performed in all patients. The granulomas were induced by oxidized cellulose polymer (n = 6), suture material (n = 3), Gelfoam (n = 1), methylmethacrylate (n = 1), and bone wax (n = 1). The mean postoperative follow-up time was 54 months (range 1-137 months). There was symptomatic improvement in all instances. Imaging studies did not demonstrate any recurrence. CONCLUSION: Despite its rarity, foreign body granuloma should be taken into consideration in the differential diagnosis of intracranial mass lesions especially in cases of suspected tumor recurrence after prior surgery. The pathogenesis of foreign body granuloma still needs further clarification. Our study demonstrates that they have good prognosis after surgical removal.
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Encéfalo/cirurgia , Granuloma de Corpo Estranho/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Idoso , Criança , Diagnóstico Diferencial , Feminino , Esponja de Gelatina Absorvível/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Suturas/efeitos adversosRESUMO
A novel magnetic metal-organic framework (MOF) consisting of MIL-101(Fe) and morin-modified magnetite nanoparticles was synthesized and utilized for the extractive speciation analysis of V(IV) and V(V) at trace levels. The magnetic MOF exhibits selectivity toward V(V) at pH = 5.8. The concentration of V(IV) can be determined after its oxidation to V(V) and extracting total vanadium. After sorption and elution steps, vanadium can be determined by ETAAS. Under the optimal conditions, the limit of detection, linearity and the relative standard deviation for V(V) are 3.0 ng L-1, 10-750 ng L-1 and 6.0%, respectively. The new method was validated by employing two certified reference materials. Finally, the method was successfully utilized for fast and selective speciation analysis of V(IV) and V(V) in water and food samples. Graphical abstract A novel functionalized magnetic metal-organic framework was synthesized and used for the speciation and preconcentration of trace amounts of vanadium.
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PURPOSE: Desmoplastic infantile gliomas (DIG) are rare tumors that occur in infants aged between 1 and 24 months. The tumor in general has a favorable prognosis after surgical resection. There are no treatment algorithms, however, for patients with multiple intracranial and intraspinal presentations. CASE REPORT: In an 11-month-old girl with a history of nystagmus, magnetic resonance imaging (MRI) demonstrated contrast-enhancing lesions in the suprasellar region, the cerebellar vermis, and the spinal axis. The tumor in the cerebellar vermis was removed via a suboccipital midline approach. The histological examination revealed a desmoplastic infantile astrocytoma (DIA) WHO grade I. Postoperatively, it was decided to adopt a wait-and-see strategy. Further development, up to 16 months after surgery, was unremarkable. Follow-up MRI showed no recurrence of the posterior fossa tumor, mild progress of the suprasellar tumor, and significant regression of the spinal tumors. CONCLUSION: DIA is a rare mostly benign brain tumor found in infants. The final diagnosis always relies on histology. Surgical resection is the recommended therapy for symptomatic tumors; however, more experience is needed to develop treatment recommendations for multiple-site tumors.
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Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Neoplasias da Coluna Vertebral/terapia , Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Feminino , Seguimentos , Humanos , Lactente , Imageamento por Ressonância Magnética , Neoplasias da Coluna Vertebral/diagnósticoRESUMO
PURPOSE: Navigated intracranial endoscopy with conventional technique usually requires sharp head fixation. In children, especially in those younger than 1 year of age and in older children with thin skulls due to chronic hydrocephalus, sharp head fixation is not possible. Here, we studied the feasibility, safety, and accuracy of electromagnetic (EM)-navigated endoscopy in a series of children, obviating the need of sharp head fixation. METHODS: Seventeen children (ten boys, seven girls) between 12 days and 16.8 years (mean age 4.3 years; median 14 months) underwent EM-navigated intracranial endoscopic surgery based on 3D MR imaging of the head. Inclusion criteria for the study were intraventricular cysts, arachnoid cysts, aqueduct stenosis for endoscopic third ventriculostomy (ETV) with distorted ventricular anatomy, the need of biopsy in intraventricular tumors, and multiloculated hydrocephalus. A total of 22 endoscopic procedures were performed. Patients were registered for navigation by surface rendering in the supine position. After confirming accuracy, they were repositioned for endoscopic surgery with the head fixed slightly on a horseshoe headholder. EM navigation was performed using a flexible stylet introduced into the working channel of a rigid endoscope. Neuronavigation accuracy was checked for deviations measured in millimeters on screenshots after the referencing procedure and during surgery in the coronal (z = vertical), axial (x = mediolateral), and sagittal (y = anteroposterior) planes. RESULTS: EM-navigated endoscopy was feasible and safe. In all 17 patients, the aim of endoscopic surgery was achieved, except in one case in which a hemorrhage occurred, blurring visibility, and we proceeded with open surgery without complications for the patient. Navigation accuracy for extracranial markers such as the tragus, bregma, and nasion ranged between 1 and 2.5 mm. Accuracy for fixed anatomical structures like the optic nerve or the carotid artery varied between 2 and 4 mm, while there was a broader variance of accuracy at the target point of the cyst itself ranging between 2 and 9 mm. CONCLUSIONS: EM-navigated endoscopy in children is a safe and useful technique enhancing endoscopic intracranial surgery and obviating the need of sharp head fixation. It is a good alternative to the common opto-electric navigation system in this age group.
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Cistos Aracnóideos/cirurgia , Fenômenos Eletromagnéticos , Endoscopia/métodos , Hidrocefalia/cirurgia , Neuronavegação/métodos , Ventriculostomia/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Posicionamento do Paciente , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The incidence of diabetes has been steadily increasing. The only curative option for diabetes is pancreas transplantation (PTx). Porcine models are valuable because of their anatomical and physiological similarities to human beings. Our aim is to introduce a simplified technique of PTx in a porcine model. METHODS: In Landrace pigs (n = 32), after median laparotomy, the pancreas was mobilized, and the portal and splenic veins were divided. The proper hepatic and splenic arteries and the bile duct were also prepared, and the duodenal bulb was prepared and stapled. The third portion of the duodenum was freed up to the ligament of Treitz and stapled, and the renal arteries were ligated. After systemic heparinization, the pancreas was perfused through the abdominal aorta with histidine-tryptophan-ketoglutarate solution. The portal and splenic veins were cut for evaluating the sufficiency of perfusion. Whole pancreaticoduodenal graft was procured along with an aortic jump graft containing mesenteric and celiac trunks. In recipients, after total pancreatectomy, the suprarenal inferior vena cava and infrarenal aorta were prepared for vascular anastomosis in an end-to-side manner. After pancreas reperfusion, duodenoduodenostomy was performed in an end-to-side manner. RESULTS: Median cold and warm ischemia times were 10 h (range, 9-14 h) and 50 min (range, 35-80 min), respectively. The hemodynamic status was stable throughout the operation. The median follow-up period was 7 days (range, 4-10). There were no major intra- and postoperative complications. CONCLUSION: By using an aortic jump graft, there was no need to perform additional arterial reconstruction resulting in a short warm ischemic and operation time. End-to-side portocaval and duodenoduodenal anastomoses make this model of PTx a very feasible method for experimental evaluations.
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Transplante de Pâncreas/métodos , Animais , Modelos Animais , Período Pós-Operatório , SuínosRESUMO
Infection associated with ventriculoperitoneal (VP) shunt implantation can be a significant problem. VP shunt infection with Serratia marcescens, a gram-negative anaerobic rod, usually is related to underlying abdominal disease. This article describes treatment of two patients suffering from a VP shunt infection with S. marcescens without underlying abdominal disease.
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Infecções do Sistema Nervoso Central/microbiologia , Infecções por Serratia/microbiologia , Serratia marcescens , Derivação Ventriculoperitoneal/efeitos adversos , Adulto , Feminino , Humanos , Infecções por Serratia/diagnóstico , Infecções por Serratia/tratamento farmacológicoRESUMO
BACKGROUND: Surgical site infections (SSIs) are among the most common postoperative complications. Glioblastoma multiforme is the most frequent malignant brain tumor with a dismal prognosis despite combined treatment. The effect of SSIs on the course of glioblastoma patients has not been fully clarified since available data are limited and partially contradictory. The aim of this study is to investigate the impact of SSIs on the course of patients with glioblastoma. METHODS: The medical records of all patients undergoing surgery for glioblastoma between 2010 and 2020 in our institution were scanned and those with surgical site infections after glioblastoma resection were identified and compared to an age-matched control group. Overall survival and progression-free survival were the primary endpoints followed by the number of hospitalizations and the length of stay in hospital. RESULTS: Out of 305 patients undergoing surgery for glioblastoma, 38 patients with postoperative surgical site infection after resection were identified and 15 (5 men and 10 women aged between 9 and 72) were included in this study. 23 patients were excluded. The control group consisted of 30 age-matched patients without SSI (18 men and 12 women). There were no significant differences in median overall survival. Progression-free survival was higher in the SSI group. The number of hospitalizations and the length of stay were significantly higher in the SSI group. CONCLUSION: Our data suggest that SSIs might reduce early recurrences without affecting overall survival. Furthermore, they might decrease health-related quality of life by doubling the total length of hospital stay.
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Glioblastoma , Infecção da Ferida Cirúrgica , Masculino , Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Glioblastoma/cirurgia , Qualidade de Vida , Tempo de Internação , Hospitalização , Fatores de RiscoRESUMO
Intracranial metastases from thyroid cancer are rare. Although the prognosis of thyroid cancer patients is generally favorable, the prognosis of patients with intracranial metastases from thyroid cancer has been considered unfavorable owing to lower survival rates among such patients compared to those without intracranial involvement. Many questions about their management remain unclear. The aim of the present study was to analyze the characteristics, treatment modalities, and outcomes of patients with brain metastases from thyroid cancer. Among 4320 patients with thyroid cancer recorded in our institutional database over a 30-year period, the data of 20 patients with brain metastasis were retrospectively collected and analyzed. The clinical characteristics, histological type of primary cancer and metastatic brain tumor, additional previous distant metastasis, treatment modalities, locations and characteristics on radiologic findings, time interval between the first diagnosis of primary thyroid cancer and brain metastasis, and survival were analyzed. Among our patient cohort, the mean age at initial diagnosis was 59.3 ± 14.1 years, and at the manifestation of diagnosis of cerebral metastasis, the mean age was found to be 64.8 ± 14.9 years. The histological types of primary thyroid cancer were identified as papillary in ten patients, follicular in seven, and poorly differentiated carcinoma in three. The average interval between the diagnosis of thyroid cancer and brain metastasis was 63.4 ± 58.4 months (range: 0-180 months). Ten patients were identified as having a single intracranial lesion, and ten patients were found to have multiple lesions. Surgical resection was primarily performed in fifteen patients, and whole-brain radiotherapy, radiotherapy, or tyrosine kinase inhibitors were applied in the remaining five patients. The overall median survival time was 15 months after the diagnosis of BMs from TC (range: 1-252 months). Patients with thyroid cancer can develop brain metastasis even many years after the diagnosis of the primary tumor. The results of our study demonstrate increased overall survival in patients younger than 60 years of age at the time of diagnosis of brain metastasis. There was no difference in survival between patients with brain metastasis from papillary carcinoma and those with follicular thyroid carcinoma.
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Crowdsourcing has been used in computational pathology to generate cell and cell nuclei annotations for machine learning. Herein, we broaden its scope to the previously unsolved challenging task of glioma cell detection. This requires multiplexed immunofluorescence microscopy due to diffuse invasiveness and exceptional similarity between glioma cells and reactive astrocytes. In four pilot experiments, we iteratively developed a task design enabling high-quality annotations by crowdworkers on Amazon Mechanical Turk. We applied majority or weighted vote and validated them against ground truth in the final setting. On the base of a YOLO convolutional neural network architecture, we used these consensus labels for training with different image representations regarding colors, intensities, and immmunohistochemical marker combinations. A crowd of 712 workers defined aggregated point annotations in 235 images with an average [Formula: see text] score of 0.627 for majority vote. The networks resulted in acceptable [Formula: see text] scores up to 0.69 for YOLOv8 on average and indicated first evidence for transferability to images lacking tumor markers, especially in IDH-wildtype glioblastoma. Our work confirms feasibility of crowdsourcing to generate labels suitable for training of machine learning tools in the challenging and clinically relevant use case of glioma microenvironment.
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Crowdsourcing , Glioblastoma , Glioma , Humanos , Microscopia de Fluorescência , Biomarcadores Tumorais , Microambiente TumoralRESUMO
OBJECTIVE: Ventriculoperitoneal shunt implantation has become standard treatment for cerebrospinal fluid diversion, besides endoscopic third ventriculostomy for certain indications. Postoperative X-ray radiography series of skull, chest and abdomen combined with cranial CT are obtained routinely in many institutions to document the shunt position and valve settings in adult patients. Measures to reduce postoperative radiation exposure are needed, however, there is only limited experience with such efforts. Here, we aim to compare routine postoperative cranial CT plus conventional radiography series (retrospective arm) with cranial CT and body scout views only (prospective arm) concerning both diagnostic quality and radiation exposure. PATIENTS AND METHODS: After introduction of an enhanced CT imaging protocol, routine skull and abdomen radiography was no longer obtained after VP shunt surgery. The image studies of 25 patients with routine postoperative cranial CT and conventional radiography (retrospective arm of study) were then compared to 25 patients with postoperative cranial CT and CT body scout views (prospective arm of study). Patient demographics such as age, sex and primary diagnosis were collected. The image quality of conventional radiographic images and computed tomography scout views images were independently analyzed by one neurosurgeon and one neuroradiologist. RESULTS: There were no differences in quality assessments according to three different factors determined by two independent investigators for both groups. There was a statistically significant difference, however, between the conventional radiography series group and the CT body scout view imaging group with regard to radiation exposure. The effective dose estimation calculation yielded a difference of 0.05â¯mSv (two-tailed t-test, pâ¯=â¯0.044) in favor of CT body scout view imaging. Furthermore, the new enhanced protocol resulted in a reduction of cost and the use of human resources. CONCLUSION: CT body scout view imaging provides sufficient imaging quality to determine shunt positioning and valve settings. With regard to radiation exposure and costs, we suggest that conventional postoperative shunt series may be abandoned.
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Exposição à Radiação , Tomografia Computadorizada por Raios X , Derivação Ventriculoperitoneal , Humanos , Feminino , Masculino , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Derivação Ventriculoperitoneal/métodos , Adulto , Exposição à Radiação/prevenção & controle , Idoso , Estudos Prospectivos , Estudos Retrospectivos , Doses de RadiaçãoRESUMO
PURPOSE: During kidney transplantation (KTx), the length of cold ischemia time (CIT) and the subsequent changes in energy metabolism may lead to variations in interstitial metabolites. Using microdialysis (MD), we evaluated the effects of a short and long CIT on changes of these metabolites. METHODS: Sixteen pigs were randomized in two identical groups, one with a short CIT and the other one with a long CIT. Using MD in the transplanted grafts, we evaluated the parenchyma concentrations of glucose, lactate, pyruvate, glutamate and glycerol in different stages. RESULTS: We noted that during the warm ischemia time (WIT) and in the early post-reperfusion phase glucose levels increased more significantly in the long CIT group and remained high until the end of monitoring. At the end of CIT and during WIT, the long CIT group had a significantly higher glycerol level, but the level dropped gradually in the late post-reperfusion phase and reached a steady state in both groups. CONCLUSIONS: The extended CIT clearly results in considerably impaired graft metabolism. The high interstitial glucose levels within hours after KTx could be considered as a marker of primary delayed function of the graft. Furthermore, the glycerol value could reflect the extent of graft injury during the ischemia time or in case of acute impairment of graft perfusion.
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Isquemia Fria , Metabolismo Energético/fisiologia , Transplante de Rim/métodos , Rim/irrigação sanguínea , Rim/fisiopatologia , Microdiálise/métodos , Animais , Glicemia/metabolismo , Ácido Glutâmico/metabolismo , Glicerol/metabolismo , Sobrevivência de Enxerto/fisiologia , Ácido Láctico/metabolismo , Ácido Pirúvico/metabolismo , Suínos , Isquemia QuenteRESUMO
Pathogenic germline variants in the DNA polymerase genes POLE and POLD1 cause polymerase proofreading-associated polyposis, a dominantly inherited disorder with increased risk of colorectal carcinomas and other tumors. POLE/POLD1 variants may result in high somatic mutation and neoantigen loads that confer susceptibility to immune checkpoint inhibitors (ICIs). To explore the role of POLE/POLD1 germline variants in glioma predisposition, whole-exome sequencing was applied to leukocyte DNA of glioma patients from 61 tumor families with at least one glioma case each. Rare heterozygous POLE/POLD1 missense variants predicted to be deleterious were identified in glioma patients from 10 (16%) families, co-segregating with the tumor phenotype in families with available DNA from several tumor patients. Glioblastoma patients carrying rare POLE variants had a mean overall survival of 21 months. Additionally, germline variants in POLD1, located at 19q13.33, were detected in 2/34 (6%) patients with 1p/19q-codeleted oligodendrogliomas, while POLE variants were identified in 2/4 (50%) glioblastoma patients with a spinal metastasis. In 13/15 (87%) gliomas from patients carrying POLE/POLD1 variants, features of defective polymerase proofreading, e.g. hypermutation, POLE/POLD1-associated mutational signatures, multinucleated cells, and increased intratumoral T cell response, were observed. In a CRISPR/Cas9-derived POLE-deficient LN-229 glioblastoma cell clone, a mutator phenotype and delayed S phase progression were detected compared to wildtype POLE cells. Our data provide evidence that rare POLE/POLD1 germline variants predispose to gliomas that may be susceptible to ICIs. Data compiled here suggest that glioma patients carrying POLE/POLD1 variants may be recognized by cutaneous manifestations, e.g. café-au-lait macules, and benefit from surveillance colonoscopy.
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Glioblastoma , Glioma , Humanos , DNA Polimerase II/genética , Domínio Catalítico , Mutação em Linhagem Germinativa , Glioma/genética , DNA , DNA Polimerase III/genéticaRESUMO
BACKGROUND: In kidney transplantation (KTx), vascular thrombosis has a major impact on morbidity and graft survival. The ischaemia, caused by thrombosis, can lead to interstitial metabolite changes. The aim of this experimental study was to create conditions in which the graft would be prone to vascular thrombosis following KTx and then to evaluate the role of microdialysis (MD) for its early detection. METHODS: Sixteen randomized pigs in the control group received heparin and immunosuppressive drugs, while the case group received none. Based on histopathological evidence of vascular thrombosis, the case group was subdivided into mildly and severely congested subgroups. Using MD, we evaluated the interstitial concentrations of glucose, lactate to pyruvate ratio, glutamate and glycerol in the transplanted grafts during different phases of KTx. RESULTS: Following reperfusion, we noted considerable changes. The severely congested subgroup showed a low and decreasing level of glucose. Only in this group did the lactate to pyruvate ratio continue to increase until the end of monitoring. The glycerol level increased continuously in the entire case group and this increase was most significant in the severely congested subgroup. In all of the study groups, glutamate concentration remained in a low steady state until the end of monitoring. CONCLUSION: MD can be an appropriate method for early detection of vascular complications after KTx. Decreasing glucose levels, increased lactate to pyruvate ratio and increased glycerol levels are appropriate indicators for early detection of vascular thromboses following KTx. Particularly, the glycerol level could predict the necessity and urgency of intervention needed to ultimately save the transplanted kidney.
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Biomarcadores/metabolismo , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Microdiálise/métodos , Trombose/diagnóstico , Análise de Variância , Animais , Biomarcadores/análise , Biópsia por Agulha , Glicemia/análise , Modelos Animais de Doenças , Diagnóstico Precoce , Ácido Glutâmico/análise , Ácido Glutâmico/metabolismo , Glicerol/análise , Glicerol/metabolismo , História do Século XIX , Imuno-Histoquímica , Transplante de Rim/métodos , Ácido Láctico/análise , Ácido Láctico/metabolismo , Ácido Pirúvico/análise , Ácido Pirúvico/metabolismo , Distribuição Aleatória , Valores de Referência , Sensibilidade e Especificidade , Sus scrofa , Suínos , Trombose/etiologiaRESUMO
BACKGROUND AND INTRODUCTION: Without adequate prophylaxis, liver transplantation (LTx) is frequently followed by hepatitis B virus (HBV) reinfection, which results in rapidly progressing liver disease and significantly decreased overall survival. In the last two decades, significant progress has been made in the prophylaxis and treatment of HBV. DISCUSSION: We present an overview of different protocols and regimens used for prophylaxis of HBV reinfection after LTx and describe the protocol implemented at our center. Following LTx, HBV reinfection can be effectively prevented by administration of anti-hepatitis B immunoglobulin (HBIg) alone or more recently in combination with antiviral nucleoside/nucleotide analogs (NUCs). Several studies reported good results with the use of HBIg alone, but combination treatment with HBIg and NUCs has proven to be a superior prophylactic regimen for HBV recurrence. At present, combination therapy (HBIg and a nucleoside or nucleotide analog) is the gold standard used in many transplantation centers. This preventive regimen reduces the risk of a recurrence of HBV infection and thereby the need for re-transplantation. Future and ongoing studies will show how long HBIg must be given after transplantation, especially when used in combination with potent antivirals, such as entecavir or tenofovir.
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Antivirais/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Hepatite B Crônica/cirurgia , Imunoglobulinas/administração & dosagem , Transplante de Fígado/métodos , Terapia Combinada , Feminino , Sobrevivência de Enxerto , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/diagnóstico , Humanos , Imunização Passiva , Lamivudina/administração & dosagem , Falência Hepática/diagnóstico , Falência Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/imunologia , Masculino , Cuidados Pós-Operatórios , Prognóstico , Medição de Risco , Prevenção Secundária , Análise de Sobrevida , Resultado do TratamentoRESUMO
We conducted a two-center retrospective survey on standard MRI features including apparent diffusion coefficient mapping (ADC) of diffuse midline gliomas H3 K27M-mutant (DMG) compared to midline glioblastomas H3 K27M-wildtype (midGBM-H3wt). We identified 39 intracranial DMG and 18 midGBM-H3wt tumors. Samples were microscopically re-evaluated for microvascular proliferations and necrosis. Image analysis focused on location, peritumoral edema, degree of contrast enhancement and DWI features. Within DMG, MRI features between tumors with or without histomorphological GBM features were compared. DMG occurred in 15/39 samples from the thalamus (38%), in 23/39 samples from the brainstem (59%) and in 1/39 tumors involving primarily the cerebellum (2%). Edema was present in 3/39 DMG cases (8%) versus 78% in the control (midGBM-H3wt) group (p < 0.001). Contrast enhancement at the tumor rim was detected in 17/39 DMG (44%) versus 67% in control (p = 0.155), and necrosis in 24/39 (62%) versus 89% in control (p = 0.060). Strong contrast enhancement was observed in 15/39 DMG (38%) versus 56% in control (p = 0.262). Apparent diffusion coefficient (ADC) histogram analysis showed significantly higher skewness and kurtosis values in the DMG group compared to the controls (p = 0.0016/p = 0.002). Minimum relative ADC (rADC) values, as well as the 10th and 25th rADC-percentiles, were lower in DMGs with GBM features within the DMG group (p < 0.001/p = 0.012/p = 0.027). In conclusion, DMG cases exhibited markedly less edema than midGBM-H3wt, even if histomorphological malignancy was present. Histologically malignant DMGs and midGBM-H3wt more often displayed strong enhancement, as well as rim enhancement, than DMGs without histomorphological malignancy. DMGs showed higher skewness and kurtosis values on ADC-histogram analysis compared to midGBM-H3wt. Lower minimum rADC values in DMGs indicated malignant histomorphological features, likely representing a more complex tissue microstructure.
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AIMS: Different surgical transection methods have been used for distal pancreatectomy (DP), but none of them has yet achieved perfect results. This study compares 2 standard transection techniques with the alternative LigaSure technique. METHODS: Forty-eight pigs underwent a DP. Sixteen animals were operated on with a scalpel followed by hand suturing. Sixteen pigs received a DP using an Endo GIA, and the pancreas of 16 pigs was transected with LigaSure. The transection surface of remnant pancreas was observed for liquid collection and abscess on postoperative day 7. RESULTS: Operating time on the day of DP was significantly different, with a shorter operating time in the stapler and LigaSure groups. The morbidity on postoperative day 7 was similar in all groups. CONCLUSION: In the present experimental animal study, LigaSure seems to be fast and safe as well as comparable with the standard transection and closure techniques in DP.