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1.
Mol Pharm ; 20(2): 1039-1049, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36548544

RESUMO

Delayed gastric emptying is known to have a major impact on drug absorption. While the test meal recommended by the FDA and EMA to study food effects represents a worst-case scenario, it does not reflect the reality of the patients. Physiologically based pharmacokinetic (PBPK) models could bridge the gap between clinical settings of food effect studies and the diverse nonclinical situations by simulating the effect of meals with different compositions and volumes. A mathematical equation based on a stretched exponential function was reparameterized to describe the gastric emptying process of mixed solid meals. The model was fitted to literature data including the gastric emptying data of 23 meals from 15 studies. Using a multiple linear regression model, we were able to predict the two function parameters from the meal characteristics caloric content and the percentage of calories derived from fat. After implementation into the PBPK software PK-Sim, the model, together with a separate compartment for liquid gastric contents, was compared to commercially available software. The model is able to simulate the gastric emptying of mixed solid meals containing drugs based on specific meal characteristics. A second compartment allows for distribution between liquid and solid components and rapid gastric emptying along the Magenstrasse.


Assuntos
Gastroparesia , Humanos , Refeições , Modelos Lineares , Fatores de Tempo , Esvaziamento Gástrico
2.
Childs Nerv Syst ; 39(8): 2079-2086, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36951979

RESUMO

PURPOSE: The perioperative treatment of hydrocephalus in pediatric posterior fossa tumors with an external ventricular drain (EVD) is the treatment of choice in our center. We analyzed our experience in using EVD concerning safety and effectivity. METHODS: This is a single-center retrospective cohort study of 100 consecutive pediatric patients who underwent resection for a newly diagnosed tumor in the posterior fossa between 2011 and 2022. RESULTS: Of the 100 patients with posterior fossa tumors, 80 patients (80%) had radiological signs of hydrocephalus at presentation, 49 patients (49%) of whom underwent placement of an EVD. In 40 patients, the EVD was inserted at a mean of 2.25 days prior to the tumor resection; 9 had the EVD inserted during tumor resection (frontal trajectory in 7 patients, occipital trajectory in 2 patients). Histology revealed pilocytic astrocytoma in 48 patients, medulloblastoma in 32, ependymoma in 11, and other histologic entities in 9 patients. Gross total/near-total resection was achieved in 46 (95.83%) of the 48 pilocytic astrocytomas, 30 (93.75%) of the 32 medulloblastomas, and 11 (100%) of the 11 ependymomas. The mean number of total days with the EVD in place was 8.61 ± 3.82 (range 2-16 days). The mean number of days with an EVD after tumor resection was 6.35 ± 3.8 (range 0-16 days). EVD-associated complications were seen in 6 patients (12.24%) including one infection. None of these resulted in a worse clinical course or any long-term sequelae. Permanent CSF diversion at 6 months after surgery was necessary in 13 patients (13%), including two VP shunt, two SD-shunt, six endoscopic third ventriculostomy (ETV), and three combined VP shunt and ETV procedures. Patients with a medulloblastoma or ependymoma had a higher rate of permanent CSF diversion needed than the group of pilocytic astrocytoma patients (27.9% versus 2.13%, p < 0.001). In patients with metastatic disease, 7 of 17 patients (41.18%) needed a permanent CSF diversion, compared to 6 of 83 patients (7.23%) in the group without metastasis (p = 0.001). CONCLUSION: The treatment of hydrocephalus in pediatric posterior fossa tumors with an EVD as a temporary measure is safe and effective, provided that a multi-professional understanding for its handling is given and there is no need for a long transport of the children.


Assuntos
Astrocitoma , Neoplasias Cerebelares , Ependimoma , Hidrocefalia , Neoplasias Infratentoriais , Meduloblastoma , Criança , Humanos , Meduloblastoma/diagnóstico por imagem , Meduloblastoma/cirurgia , Meduloblastoma/complicações , Estudos Retrospectivos , Neoplasias Infratentoriais/diagnóstico por imagem , Neoplasias Infratentoriais/cirurgia , Neoplasias Infratentoriais/complicações , Ventriculostomia/métodos , Ependimoma/cirurgia , Ependimoma/complicações , Astrocitoma/diagnóstico por imagem , Astrocitoma/cirurgia , Astrocitoma/complicações , Hidrocefalia/cirurgia , Hidrocefalia/complicações , Neoplasias Cerebelares/cirurgia
3.
Proc Natl Acad Sci U S A ; 117(37): 22800-22804, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32873640

RESUMO

Terrorist attacks often fuel online hate and increase the expression of xenophobic and antiminority messages. Previous research has focused on the impact of terrorist attacks on prejudiced attitudes toward groups linked to the perpetrators as the cause of this increase. We argue that social norms can contain the expression of prejudice after the attacks. We report the results of a combination of a natural and a laboratory-in-the-field (lab-in-the-field) experiment in which we exploit data collected about the occurrence of two consecutive Islamist terrorist attacks in Germany, the Würzburg and Ansbach attacks, in July 2016. The experiment compares the effect of the terrorist attacks in hate speech toward refugees in contexts where a descriptive norm against the use of hate speech is evidently in place to contexts in which the norm is ambiguous because participants observe antiminority comments. Hate toward refugees, but not toward other minority groups, increased as a result of the attacks only in the absence of a strong norm. These results imply that attitudinal changes due to terrorist attacks are more likely to be voiced if norms erode.

4.
J Cardiothorac Vasc Anesth ; 36(8 Pt A): 2339-2343, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34879925

RESUMO

OBJECTIVE: The aim of this study was to identify perioperative risk factors associated with intensive care unit readmission and in-hospital death after cardiac surgery. DESIGN: Retrospective analysis using a multivariate regression model to identify independent risk factors for intensive care unit [ICU] readmission and in-hospital mortality. SETTING: The study was carried out in a single tertiary-care hospital. PARTICIPANTS: This was an analysis of 2,789 adult patients. INTERVENTIONS: All patients underwent cardiac surgery and were admitted to the intensive care unit perioperatively at the General Hospital Vienna. MEASUREMENTS AND MAIN RESULTS: Among the 2,789 patients included in the analysis, 167 (6%) were readmitted to the intensive care unit during the same hospital stay. Preoperative risk factors associated with ICU readmission included end-stage renal failure (odds ratio [OR] 2.80, 95% CI: 1.126-6.964), arrhythmia (OR 1.59, 95% CI: 1.019-2.480), chronic obstructive pulmonary disease (OR 1.51, 95% CI: 1.018-2.237), age >80 (OR 2.55, 95% CI: 1.189-5.466), and European System for Cardiac Operative Risk Evaluation II >8 (OR 1.40, 95% CI: 1.013-1.940). Readmitted patients were more likely to die than nonreadmitted patients (OR 5.3, 95% CI: 3.284-8.558). In-hospital mortality in readmitted patients was 19.2%, whereas that in the nonreadmitted study population was 5.1%. CONCLUSION: Preoperative risk assessment is crucial for identifying cardiac surgery patients at risk of ICU readmission and in-hospital death. The potentially modifiable risk factors pinpointed by this study call for the optimization of care before surgery and after ICU discharge.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Readmissão do Paciente , Adulto , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Estudos Retrospectivos , Fatores de Risco
5.
Proc Natl Acad Sci U S A ; 115(11): 2722-2727, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29483253

RESUMO

Recent waves of immigration to Western nations have fueled a debate over the consequences of ethnic diversity for social cohesion. One prominent argument in this debate holds that diversity is detrimental to trust and cooperation because individuals in heterogeneous communities face difficulties in enforcing social norms across ethnic lines. We examine this proposition in a field experiment involving real-life interactions among residents of multiethnic German neighborhoods. We find significant ethnic asymmetries in the pattern of norm enforcement: Members of the majority "native" German population are more active in sanctioning norm violations, while ethnic minorities are more likely to find themselves the target of sanctions. We interpret these results in light of prevailing status inequalities between ethnic minorities and the native majority. We further calculate that, as a result of ethnic discrimination, social control is likely to rise in communities with moderate minority population shares.


Assuntos
Etnicidade/psicologia , Normas Sociais/etnologia , Adolescente , Adulto , Diversidade Cultural , Emigração e Imigração , Feminino , Humanos , Masculino , Grupos Minoritários/psicologia , Características de Residência , Adulto Jovem
6.
Acta Neurochir (Wien) ; 163(2): 441-446, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009932

RESUMO

OBJECTIVE: Cranioplasty (CP) is considered as a straightforward and technically unchallenging operation; however, complication rates are high reaching up to 56%. Presence of a ventriculoperitoneal shunt (VPS) and timing of CP are reported risk factors for complications. Pressure gradients and scarring at the site of the cranial defect seem to be critical in this context. The authors present their experiences and lessons learned. METHODS: A consecutive series of all patients who underwent CP at the authors' institution between 2002 and 2017 were included in this retrospective analysis. Complications were defined as all events that required reoperation. Logistic regression analysis and chi-squared test were conducted to evaluate the complication rates according to suspected risk factors. RESULTS: A total of 302 patients underwent cranioplasty between 2002 and 2017. The overall complication rate was 17.5%. Complications included epi-/subdural fluid collection (7.3%) including hemorrhage (4.6%) and hygroma (2.6%), bone graft resorption (5.3%), bone graft infection (2.0%), and hydrocephalus (5.7%). Overall, 57 patients (18.9%) had undergone shunt implantation prior to CP. The incidence of epi-/subdural fluid collection was 19.3% in patients with VPS and 4.5% in patients without VPS, OR 5.1 (95% CI 2.1-12.4). Incidence of hygroma was higher in patients who underwent early CP. Patients with temporary shunt ligation for CP did not suffer from complications. CONCLUSION: CP in patients with a VPS remains a high-risk procedure. Any effort to understand the pressure dynamics and to reduce factors that may trigger the formation of a large epidural space must be undertaken.


Assuntos
Craniectomia Descompressiva/efeitos adversos , Craniectomia Descompressiva/métodos , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Derivação Ventriculoperitoneal/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Reabsorção Óssea/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Hidrocefalia/cirurgia , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Crânio/cirurgia , Adulto Jovem
7.
Acta Neurochir (Wien) ; 163(5): 1437-1442, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33523299

RESUMO

BACKGROUND: New-onset seizures after cranioplasty (NOSAC) are reported to be a frequent complication of cranioplasty (CP) after decompressive hemicraniectomy (DHC). There are considerable differences in the incidence of NOSAC and contradictory data about presumed risk factors in the literature. We suggest NOSAC to be a consequence of patients' initial condition which led to DHC, rather than a complication of subsequent CP. We conducted a retrospective analysis to verify our hypothesis. METHODS: The medical records of all patients ≥ 18 years who underwent CP between 2002 and 2017 at our institution were evaluated including incidence of seizures, time of seizure onset, and presumed risk factors. Indication for DHC, type of implant used, timing of CP, patient age, presence of a ventriculoperitoneal shunt (VP shunt), and postoperative complications were compared between patients with and without NOSAC. RESULTS: A total of 302 patients underwent CP between 2002 and 2017, 276 of whom were included in the outcome analysis and the incidence of NOSAC was 23.2%. Although time between DHC and CP differed significantly between DHC indication groups, time between DHC and seizure onset did not differ, suggesting the occurrence of seizures to be independent of the procedure of CP. Time of follow-up was the only factor associated with the occurrence of NOSAC. CONCLUSION: New-onset seizures may be a consequence of the initial condition leading to DHC rather than of CP itself. Time of follow-up seems to play a major role in detection of new-onset seizures.


Assuntos
Craniectomia Descompressiva/efeitos adversos , Complicações Pós-Operatórias/etiologia , Convulsões/etiologia , Derivação Ventriculoperitoneal/efeitos adversos , Adulto , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Convulsões/epidemiologia , Crânio/cirurgia
8.
Acta Neurochir (Wien) ; 163(12): 3321-3336, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34674027

RESUMO

OBJECTIVE: To analyze characteristics associated with long-term pain relief after microvascular decompression (MVD) for trigeminal neuralgia (TGN). Description of associated morbidity and complication avoidance. METHODS: One hundred sixty-five patients with TGN underwent 171 MVD surgeries at the authors' institution. Patient characteristics and magnetic resonance imaging (MRI) datasets were obtained through the hospital's archiving system. Patients provided information about pre- and post-operative pain characteristics and neurologic outcome. Favorable outcome was defined as a Barrow Neurological Institute (BNI) pain intensity score of I to III with post-operative improvement of I grade. RESULTS: Type of TGN pain with purely paroxysmal pain (p = 0.0202*) and TGN classification with classical TGN (p = 0.0372*) were the only significant predictors for long-term pain relief. Immediate pain relief occurred in 90.6% of patients with a recurrence rate of 39.4% after 3.5 ± 4.6 years. MRI reporting of a neurovascular conflict had a low negative predictive value of 39.6%. Mortality was 0% with major complications observed in 8.2% of patients. Older age was associated with lower complication rates (p = 0.0009***). Re-MVD surgeries showed improved long-term pain relief in four out of five cases. CONCLUSIONS: MVD is a safe and effective procedure even in the elderly. It has the unique potential to cure TGN if performed on a regular basis, and if key surgical steps are respected. Early MVD should be offered in case of medical treatment failure and paroxysmal pain symptoms. The presence of a neurovascular conflict on MRI is not mandatory. In case of recurrence, re-MVD is a good treatment option that should be discussed with patients. HIGHLIGHTS: • Long-term analysis of pain relief after MVD. • Positive predictors for outcome: classical TGN and purely paroxysmal pain. • Presence of neurovascular conflict in MRI is not mandatory for MVD surgery. • Analysis of complications and surgical nuances for avoidance. • MVD is a safe procedure also in the elderly.


Assuntos
Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo , Idoso , Humanos , Manejo da Dor , Medição da Dor , Dor Pós-Operatória , Estudos Retrospectivos , Resultado do Tratamento , Neuralgia do Trigêmeo/cirurgia
9.
Philos Trans R Soc Lond B Biol Sci ; 379(1897): 20230030, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38244595

RESUMO

The USA is fast becoming a 'majority-minority' country in which Whites will no longer comprise the numerically dominant racial group. Prior studies have linked Whites' status decline to heightened in-group solidarity and the feeling that Whites, as a group, face growing discrimination. In the light of these findings, we examine the extent to which a social norm controlling anti-White prejudice is now discernible in the USA. Drawing from an original survey measuring Americans' reactions to racially-offensive speech, we examine second-order beliefs about the social inappropriateness of offensive statements targeting White Americans. We find that White Americans (in comparison to non-Whites) are indeed more likely to profess a social norm governing anti-white prejudice. The pattern is most discernible among white Republicans whom we expect to be most fearful of demographic change. This article is part of the theme issue 'Social norm change: drivers and consequences'.


Assuntos
Grupos Minoritários , Preconceito , Humanos , Estados Unidos , Emoções , Medo , Brancos
10.
Eur J Pharm Sci ; 198: 106788, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38705421

RESUMO

Physiologically based pharmacokinetic (PBPK) models can help to understand the effects of gastric emptying on pharmacokinetics and in particular also provide a platform for understanding mechanisms of food effects, as well as extrapolation between different postprandial conditions, whether standardized clinical or patient-oriented, non-clinical conditions. By integrating biorelevant dissolution data from the GastroDuo dissolution model into a previously described mechanistic model of fed-state gastric emptying, we simulated the effects of a high-calorie high-fat meal on the pharmacokinetics of sildenafil, febuxostat, acetylsalicylic acid, theobromine and caffeine. The model was able to simulate the variability in Cmax and tmax caused by the presence of the stomach road. The main influences investigated to affect the gastric emptying process were drug solubility (theobromine and caffeine), tablet dissolution rate (acetylsalicylic acid) and sensitivity to gastric motility (sildenafil and febuxostat). Finally, we showed how PBPK models can be used to extrapolate pharmacokinetics between different prandial states using theobromine as an example with results from a clinical study being presented.


Assuntos
Simulação por Computador , Esvaziamento Gástrico , Modelos Biológicos , Período Pós-Prandial , Solubilidade , Esvaziamento Gástrico/fisiologia , Período Pós-Prandial/fisiologia , Humanos , Febuxostat/farmacocinética , Febuxostat/química , Teobromina/farmacocinética , Teobromina/química , Cafeína/farmacocinética , Cafeína/química , Cafeína/administração & dosagem , Citrato de Sildenafila/farmacocinética , Citrato de Sildenafila/química , Liberação Controlada de Fármacos , Aspirina/farmacocinética , Aspirina/química , Aspirina/administração & dosagem
11.
World Neurosurg ; 182: e253-e261, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38008172

RESUMO

OBJECTIVE: To evaluate the neurosurgical and economic effectiveness of a newly launched intraoperative high-field (3T) magnetic resonance imaging (MRI) suite for pediatric tumor and epilepsy neurosurgery. METHODS: Altogether, 148 procedures for 124 pediatric patients (mean age, 8.7 years; range, 0-18 years) within a 2.5-year period were undertaken in a 2-room intraoperative MRI (iopMRI) suite. Surgery was performed mainly for intractable epilepsy (n = 81; 55%) or pediatric brain tumors (n = 65; 44%) in the supine (n = 113; 76%) and prone (n = 35; 24%) positions. The mean time of iopMRI from draping to re-surgery was 50 minutes. RESULTS: IopMRI was applied not in all but in 64 of 148 procedures (43%); in 45 procedures (31%), iopMRI was estimated unnecessary at the end of surgery based on the leading surgeon's decision. In the remaining 39 procedures (26%), ultra-early postoperative MRI was carried out after closure with the patient still sterile in the head coil. Of the 64 procedures with iopMRI, second-look surgery was performed in 26% (in epilepsy surgery in 17%, in tumor surgery in 9%). We did not encounter any infections, wound revisions, or position-related or anesthesiology-related complications. CONCLUSIONS: We used iopMRI in less than half of pediatric tumor and epilepsy surgery for which it was scheduled initially. Therefore, high costs argue against its routine use in pediatric neurosurgery, although it optimized surgical results in one quarter of patients and met high safety standards.


Assuntos
Neoplasias Encefálicas , Epilepsia , Neurocirurgia , Humanos , Criança , Centros de Atenção Terciária , Neuronavegação/métodos , Imageamento por Ressonância Magnética/métodos , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Epilepsia/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/complicações
12.
Brain Spine ; 4: 102755, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510599

RESUMO

Introduction: Open resective surgery remains the main treatment modality for refractory epilepsy, but is often considered a last resort option due to its invasiveness. Research question: This manuscript aims to provide an overview on traditional as well as minimally invasive surgical approaches in modern state of the art epilepsy surgery. Materials and methods: This narrative review addresses both historical and contemporary as well as minimal invasive surgical approaches in epilepsy surgery. Peer-reviewed published articles were retrieved from PubMed and Scopus. Only articles written in English were considered for this work. A range of traditional and minimally invasive surgical approaches in epilepsy surgery were examined, and their respective advantages and disadvantages have been summarized. Results: The following approaches and techniques are discussed: minimally invasive diagnostics in epilepsy surgery, anterior temporal lobectomy, functional temporal lobectomy, selective amygdalohippocampectomy through a transsylvian, transcortical, or subtemporal approach, insulo-opercular corticectomies compared to laser interstitial thermal therapy, radiofrequency thermocoagulation, stereotactic radiosurgery, neuromodulation, high intensity focused ultrasound, and disconnection surgery including callosotomy, hemispherotomy, and subpial transections. Discussion and conclusion: Understanding the benefits and disadvantages of different surgical approaches and strategies in traditional and minimal invasive epilepsy surgery might improve the surgical decision tree, as not all procedures are appropriate for all patients.

13.
Eur J Pharm Biopharm ; 198: 114277, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582180

RESUMO

BACKGROUND: The transit and distribution pattern of fluids in the small intestine is a key parameter for the dissolution and absorption of drugs. Although some information is known about the small intestinal water content after administration of fluid volumes and meals, the intestinal transit of orally ingested fluids and solutions has been barely investigated. The aim of this three-arm, cross-over, 9-subject human study was to investigate the transit of orally ingested water in the small intestine under fasting and postprandial conditions using MRI. To identify the ingested water, manganese gluconate, which can be identified with T1-weighted MRI sequences, was added as a marker. Using Horos (DICOM software), quantification of the distribution of Mn2+ ions in the gastrointestinal tract in fasted versus fed state (standard meal by FDA guidance and a light meal) was possible. The distribution and approximate wetted intestinal length was very similar in the fasting and postprandial states, suggesting rapid transport of water ingested after a meal through the chyme-filled small intestine in continuation of the "Magenstrasse" (stomach road). In some subjects, manganese gluconate reached deeper parts of the small intestine even more quickly in the postprandial state than in the fasting arm of the study. A deeper understanding of the behaviour of solutes in the gastrointestinal tract is fundamental to a mechanistic explanation for the kinetic interaction between food and drug intake (food effects).


Assuntos
Esvaziamento Gástrico , Gluconatos , Intestino Delgado , Humanos , Imageamento por Ressonância Magnética , Água , Estudos Cross-Over
14.
Seizure ; 122: 19-25, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39303463

RESUMO

PURPOSE: Imaging and resection strategies for pediatric gangliogliomas (GG) and dysembryoplastic neuroepitheliomas (DNET) presenting with epilepsy were retrospectively analyzed in a consecutive institutional series of surgically treated patients. METHODS: Twenty-two children (median 8 years, 3-18 years) presented with seizures for 30 months median (14-55.2 months) due to a histologically verified GG/DNET. RESULTS: There were 20 GG and 2 DNT, 68 % located temporal, 32 % extra-temporal. Seizure history was significantly longer in temporal cases (38 versus 14 months median, p < 0.01). MRI contrast enhancement was present in 50 % and methionine (MET) positron emission tomography (PET) uptake in 70 % (standard uptake values (SUVs) 2.92 mean, from 1.6 to 6.4). 27 % had glucose PET hypometabolism. Primarily, in temporal GG, ECoG (electrocorticography) -guided lesionectomies were performed in 87 % and antero-mesial temporal lobe resections (AMTLR) in 13 %, whereas in extra-temporal GG/DNETs, lesionectomies were performed in 100 %. ILAE Class 1 seizure outcome was primarily achieved in 73 % of the temporal cases, and was increased to 93 % by performing six repeat surgeries using AMTLR. Extratemporal patients experienced ILAE Class 1 seizure outcomes in 86 % without additional surgeries, although harboring significantly more residual tumor (p < 0.005, mean follow-up 28 months). CONCLUSION: In children, MET PET imaging for suspected GG is proposed preoperatively showing a high diagnostic sensitivity and an option to delineate the lesions for navigated resection, whereas MRI contrast behavior was of no differential diagnostic use. As a surgical strategy we propose primarily lesionectomies for extratemporal but AMTLR for temporal GG respecting eloquent brain areas.

15.
Eur J Pharm Biopharm ; 199: 114313, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718842

RESUMO

The aim of the present study was to investigate the gastroretentive capacity of different formulation principles. This was indirectly determined by the absorption behavior of caffeine from the dosage forms. A slow and continuous appearance of caffeine in the saliva of healthy volunteers was used as a parameter for a prolonged gastric retention time. For this purpose, a four-way study was conducted with twelve healthy volunteers using the following test procedures: (1) Effervescent granules with 240 mL of still water administered in fed state, (2) effervescent granules with 20 mL of still water in fed state, (3) extended release (ER) tablet with 240 mL of still water in fed state, and (4) effervescent granules with 240 mL of still water in fasted state. The initial rise of the caffeine concentrations was more pronounced after the intake of the effervescent granules in the fed state compared to that of the ER tablets. However, tmax tended to be shorter in the fed study arms following administration of the ER tablet compared to the granules. Overall, the application of active pharmaceutical ingredients formulated as effervescent granules seems to be a promising approach to increase their gastric residence time after intake in fed state.


Assuntos
Cafeína , Preparações de Ação Retardada , Comprimidos , Humanos , Cafeína/administração & dosagem , Cafeína/farmacocinética , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Masculino , Adulto , Adulto Jovem , Feminino , Jejum , Administração Oral , Saliva/metabolismo , Saliva/química , Voluntários Saudáveis , Mucosa Gástrica/metabolismo , Estudos Cross-Over , Estômago/efeitos dos fármacos
16.
Front Robot AI ; 11: 1355409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933084

RESUMO

Objectives: We recently introduced a frameless, navigated, robot-driven laser tool for depth electrode implantation as an alternative to frame-based procedures. This method has only been used in cadaver and non-recovery studies. This is the first study to test the robot-driven laser tool in an in vivo recovery animal study. Methods: A preoperative computed tomography (CT) scan was conducted to plan trajectories in sheep specimens. Burr hole craniotomies were performed using a frameless, navigated, robot-driven laser tool. Depth electrodes were implanted after cut-through detection was confirmed. The electrodes were cut at the skin level postoperatively. Postoperative imaging was performed to verify accuracy. Histopathological analysis was performed on the bone, dura, and cortex samples. Results: Fourteen depth electrodes were implanted in two sheep specimens. Anesthetic protocols did not show any intraoperative irregularities. One sheep was euthanized on the same day of the procedure while the other sheep remained alive for 1 week without neurological deficits. Postoperative MRI and CT showed no intracerebral bleeding, infarction, or unintended damage. The average bone thickness was 6.2 mm (range 4.1-8.0 mm). The angulation of the planned trajectories varied from 65.5° to 87.4°. The deviation of the entry point performed by the frameless laser beam ranged from 0.27 mm to 2.24 mm. The histopathological analysis did not reveal any damage associated with the laser beam. Conclusion: The novel robot-driven laser craniotomy tool showed promising results in this first in vivo recovery study. These findings indicate that laser craniotomies can be performed safely and that cut-through detection is reliable.

17.
J Neurol ; 271(2): 804-818, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37805665

RESUMO

OBJECTIVE: Recently, the 7 Tesla (7 T) Epilepsy Task Force published recommendations for 7 T magnetic resonance imaging (MRI) in patients with pharmaco-resistant focal epilepsy in pre-surgical evaluation. The objective of this study was to implement and evaluate this consensus protocol with respect to both its practicability and its diagnostic value/potential lesion delineation surplus effect over 3 T MRI in the pre-surgical work-up of patients with pharmaco-resistant focal onset epilepsy. METHODS: The 7 T MRI protocol consisted of T1-weighted, T2-weighted, high-resolution-coronal T2-weighted, fluid-suppressed, fluid-and-white-matter-suppressed, and susceptibility-weighted imaging, with an overall duration of 50 min. Two neuroradiologists independently evaluated the ability of lesion identification, the detection confidence for these identified lesions, and the lesion border delineation at 7 T compared to 3 T MRI. RESULTS: Of 41 recruited patients > 12 years of age, 38 were successfully measured and analyzed. Mean detection confidence scores were non-significantly higher at 7 T (1.95 ± 0.84 out of 3 versus 1.64 ± 1.19 out of 3 at 3 T, p = 0.050). In 50% of epilepsy patients measured at 7 T, additional findings compared to 3 T MRI were observed. Furthermore, we found improved border delineation at 7 T in 88% of patients with 3 T-visible lesions. In 19% of 3 T MR-negative cases a new potential epileptogenic lesion was detected at 7 T. CONCLUSIONS: The diagnostic yield was beneficial, but with 19% new 7 T over 3 T findings, not major. Our evaluation revealed epilepsy outcomes worse than ILAE Class 1 in two out of the four operated cases with new 7 T findings.


Assuntos
Epilepsias Parciais , Epilepsia , Substância Branca , Humanos , Adulto , Consenso , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/cirurgia , Imageamento por Ressonância Magnética/métodos , Substância Branca/patologia
18.
J Neurosurg Sci ; 67(3): 344-350, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33709659

RESUMO

BACKGROUND: Drugs that inhibit blood clot formation are a risk factor for the development and recurrence of chronic subdural hematoma (cSDH). The use of non-steroidal anti-inflammatory drug (NSAID) was associated with higher bleeding rates in non-neurosurgical patients, but their influence on cranial hematomas is unclear. We sought to better describe the hazard associated with their use in cSDH patients and find additional risk factors. METHODS: We performed a retrospective analysis of patients undergoing burr hole drainage for cSDH over a period of 15 years. Demographic and surgical details were extracted from individual patient records. Patients were followed for up to 90 days with SDH recurrence requiring repeat surgery as the primary endpoint. Univariate and multivariate Cox regression models were performed to identify risk factors and their effect size. RESULTS: We included 361 patients, who underwent burr hole drainage for cSDH. Recurrences occurred in 73 patients (20.2%) after a median time period of 18 days. Sixty-six patients in our cohort were taking NSAIDs perioperatively. The recurrence rate was not higher in NSAID users compared to other patients with 18.2% and 20.7%, respectively. 23.5% of men, yet only 12.7% of women had recurrences revealing male sex as a risk factor in a uni- and multivariate regression. Not placing a drain was a risk factor for early recurrences, which resulted in a prolonged hospital stay. CONCLUSIONS: We identified male sex as a risk factor for cSDH recurrence after burr hole drainage, while perioperative NSAID use did not increase recurrence rates.


Assuntos
Hematoma Subdural Crônico , Humanos , Masculino , Feminino , Estudos Retrospectivos , Hematoma Subdural Crônico/tratamento farmacológico , Hematoma Subdural Crônico/cirurgia , Trepanação/métodos , Drenagem/métodos , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios
19.
World Neurosurg ; 179: 146-152, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37634664

RESUMO

OBJECTIVE: Magnetic resonance thermography-guided laser interstitial thermal therapy (LITT) provides a minimally invasive treatment option in children with central nervous system tumors or medically intractable epilepsy. However, transporting anesthetized children between an operating room (OR) and a radiologic suite creates logistical challenges. Thus we describe advantages of using a 2-room intraoperative magnetic resonance imaging (MRI) concept for LITT. METHODS: Patients were pinned in a head frame that doubles as the lower part of the MRI head coil. Preoperative MRI was performed for accurate neuronavigation, after which laser fibers were stereotactically implanted. Transport between OR and MRI was achieved by sliding the top of the OR table onto a trolly. RESULTS: We performed 12 procedures in 11 children, mean age 7.1 years (range: 2 to 14 years). Ten children suffered from medically intractable epilepsy, and 1 child had a pilocytic midbrain astrocytoma. Two fibers were placed in 8 and 1 fiber in 4 procedures. Mean entry point and target errors were 2.8 mm and 3.4 mm, respectively. Average transfer time from OR to MRI and vice versa was 9 minutes (±1 minute, 40 seconds). Altogether, 50% of the seizure patients were seizure free (Engel grade I) at 22 months' follow-up time. One hemorrhagic event, which could be managed nonoperatively, occurred. We recorded no surgical site or intracranial infections. CONCLUSIONS: All LITT procedures were successfully carried out with head frame in the sterile environment. The intraoperative MRI suite proved to be advantageous for minimally invasive procedures, especially in young children resulting in short transports while maintaining high accuracy and safety.


Assuntos
Epilepsia Resistente a Medicamentos , Terapia a Laser , Neoplasias , Humanos , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Técnicas Estereotáxicas , Terapia a Laser/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias/cirurgia , Lasers , Resultado do Tratamento
20.
J Neurosurg Sci ; 67(4): 507-511, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34763388

RESUMO

BACKGROUND: The purpose of this study was to identify independent risk factors for incidental durotomy (ID) during decompressive lumbar spine surgery, and to describe its treatment. METHODS: This retrospective review includes 650 patients who underwent lumbar decompression at a tertiary institution between January 2015 and October 2019. Data collection was obtained through one independent researcher. The incidence rate and treatment of ID was evaluated by a chart review of operative notes, patient charts, physiotherapy reports, and nursing reports. RESULTS: The incidence rate of ID was 12.6%. The most common reason for admission was disc herniation (63.2%), followed by vertebral stenosis (22.1%). ID resulted in significantly longer operation time (P=0.0001) and length of hospitalization (P=0.0001). A correlation between ID and patient's diagnosis (P=0.0078) as well as the chosen type of surgery (P=0.0404) with an Odds Ratio to cause ID of 1.9 for laminectomy and 1.6 for undercutting compared to microdiscectomy were found. However, age, sex, surgeon experience, lumbar level, revision surgery, as well as multilevel surgery were not significantly correlated with the incidence of ID. Dural tears were closed with dural sealant (47.2%), polyester 4-0 sutures (11.1%) or a combination of both (37.5%) and the majority of patients had bed rest of at least two days. By usage of these treatment methods no patient needed reoperation. CONCLUSIONS: Diagnosis of vertebrostenosis as well as laminectomy were significantly correlated with the incidence of ID. Treatment with intraoperative closure and postoperative bed rest even though not standardized led to complication free outcomes.


Assuntos
Vértebras Lombares , Complicações Pós-Operatórias , Humanos , Incidência , Complicações Pós-Operatórias/epidemiologia , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fatores de Risco , Descompressão , Dura-Máter/cirurgia
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