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1.
J Neurophysiol ; 130(5): 1142-1149, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37791381

ABSTRACT

Allocentric and egocentric reference frames are used to code the spatial position of action targets in reference to objects in the environment, i.e., relative to landmarks (allocentric), or the observer (egocentric). Previous research investigated reference frames in isolation, for example, by shifting landmarks relative to the target and asking participants to reach to the remembered target location. Systematic reaching errors were found in the direction of the landmark shift and used as a proxy for allocentric spatial coding. Here, we examined the interaction of both allocentric and egocentric reference frames by shifting the landmarks as well as the observer. We asked participants to encode a three-dimensional configuration of balls and to reproduce this configuration from memory after a short delay followed by a landmark or an observer shift. We also manipulated the number of landmarks to test its effect on the use of allocentric and egocentric reference frames. We found that participants were less accurate when reproducing the configuration of balls after an observer shift, which was reflected in larger configurational errors. In addition, an increase in the number of landmarks led to a stronger reliance on allocentric cues and a weaker contribution of egocentric cues. In sum, our results highlight the important role of egocentric cues for allocentric spatial coding in the context of memory-guided actions.NEW & NOTEWORTHY Objects in our environment are coded relative to each other (allocentrically) and are thought to serve as independent and reliable cues (landmarks) in the context of unreliable egocentric signals. Contrary to this assumption, we demonstrate that egocentric cues alter the allocentric spatial memory, which could reflect recently discovered interactions between allocentric and egocentric neural processing pathways. Furthermore, additional landmarks lead to a higher contribution of allocentric and a lower contribution of egocentric cues.


Subject(s)
Cues , Spatial Memory , Humans , Psychomotor Performance , Space Perception , Mental Recall
2.
Acta Neurochir (Wien) ; 165(11): 3521-3527, 2023 11.
Article in English | MEDLINE | ID: mdl-37715821

ABSTRACT

PURPOSE: Pedicle subtraction osteotomy (PSO) as an invasive procedure with high reoperation and complication rates in an often elderly population has often been questioned. The purpose of our study was to evaluate the impact of PSO for sagittal imbalance (SI) on patient-reported outcomes including self-reported satisfaction and health-related quality of life 2 years postoperatively. METHODS: Consecutive patients who underwent correction of their spinal deformity by thoracolumbar PSO were assessed using self-reporting questionnaires 2 years postoperatively. Outcome was measured by visual analogue scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and EQ-5D scores. Additionally, a Patient Satisfaction Index (PSI) rated in four grades (A: very satisfied to D: not satisfied), walking range, and the Timed Up and Go (TUG) Test were evaluated. RESULTS: Sixty-five patients were included, and each parameter was assessed preoperatively and 24 months postoperatively. The intervention led to significant improvements in back pain (8.1 ± 1.2 vs. 2.9 ± 1.9; p < 0.001), as well as ODI scores (57.7 ± 13.9 vs. 32.6 ± 18.9; p < 0.001), walking range (589 ± 1676 m vs. 3265 ± 3405 m; p < 0.001), and TUG (19.2 s vs. 9.7 s; p < 0.05). 90.7% of patients (n = 59/65) reported a PSI grade "A" or "B" 24 months postoperatively. CONCLUSION: Patient satisfaction 24 months after PSO for SI is high. Quality of life improved significantly by restoring sagittal balance.


Subject(s)
Kyphosis , Spinal Fusion , Humans , Aged , Quality of Life , Osteotomy/adverse effects , Osteotomy/methods , Patient Satisfaction , Back Pain , Walking , Retrospective Studies , Spinal Fusion/methods , Treatment Outcome , Lumbar Vertebrae/surgery , Kyphosis/surgery , Thoracic Vertebrae/surgery
3.
Neuron ; 111(6): 888-902.e8, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36608692

ABSTRACT

The adult CA1 region of the hippocampus produces coordinated neuronal dynamics with minimal reliance on its extrinsic inputs. By contrast, neonatal CA1 is tightly linked to externally generated sensorimotor activity, but the circuit mechanisms underlying early synchronous activity in CA1 remain unclear. Here, using a combination of in vivo and ex vivo circuit mapping, calcium imaging, and electrophysiological recordings in mouse pups, we show that early dynamics in the ventro-intermediate CA1 are under the mixed influence of entorhinal (EC) and thalamic (VMT) inputs. Both VMT and EC can drive internally generated synchronous events ex vivo. However, movement-related population bursts detected in vivo are exclusively driven by the EC. These differential effects on synchrony reflect the different intrahippocampal targets of these inputs. Hence, cortical and subcortical pathways act differently on the neonatal CA1, implying distinct contributions to the development of the hippocampal microcircuit and related cognitive maps.


Subject(s)
Hippocampus , Neurons , Animals , Mice , Hippocampus/physiology , Neurons/physiology , Thalamus , Entorhinal Cortex/physiology , CA1 Region, Hippocampal/physiology
4.
Int J Neurosci ; 133(2): 159-168, 2023 Feb.
Article in English | MEDLINE | ID: mdl-33635748

ABSTRACT

Aim: Cancer patients undergoing chemotherapy report cognitive changes collectively termed "chemo brain." Neuroinflammation is among the factors believed to contribute to "chemo brain" suggesting a potential beneficial role for anti-inflammatory drugs in cancer patients undergoing chemotherapy. We investigated whether the non-steroidal anti-inflammatory drug naproxen influenced hippocampal inflammation in non-tumor bearing female mice receiving the chemotherapy drug cyclophosphamide (CP).Materials and methods: Intact and ovariectomized C57BL/6 mice were used to examine potential role of ovarian hormones on neuroinflammation. The mice were placed on naproxen (375 ppm) or control diet, and a week later CP (100 mg/kg; i.p.) was administered every 3 days for 2 weeks. We analyzed hippocampal inflammatory biomarkers, anxiety-like behavior, spatial working memory, exploratory behavior, spontaneous locomotor activity and depression-like behavior.Results: CP produced significant effects on anti-inflammatory but not pro-inflammatory biomarkers. However, CP and naproxen in combination produced significant effects on both pro- and anti- inflammatory biomarkers. Naproxen and ovariectomy individually produced significant effects on pro- and anti-inflammatory biomarkers as well. Working memory and depression-like behavior were not significantly influenced by CP, naproxen or ovariectomy individually although CP and ovariectomy produced significant interaction effects on depression-like behavior. Exploratory behavior and locomotor activity showed significant effects of CP, and interaction between CP and naproxen was significant for locomotor activity.Conclusions: Ovariectomy, naproxen and a combination of CP and naproxen upregulate hippocampal pro- and anti- inflammatory biomarkers. None of the factors individually produce significant behavioral changes that could be consistent with chemo brain, although CP and ovariectomy in combination produced significant effects on depression-like behavior, a co-morbidity of chemo brain.


Subject(s)
Naproxen , Neuroinflammatory Diseases , Mice , Female , Animals , Naproxen/pharmacology , Naproxen/therapeutic use , Mice, Inbred C57BL , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Hippocampus
5.
Sci Rep ; 12(1): 14084, 2022 08 18.
Article in English | MEDLINE | ID: mdl-35982112

ABSTRACT

The sensations to own and control a body as well as being located in a body describe the relation between ourselves and our body, termed embodiment. Embodiment plays a central role in our everyday actions. However, its assessment is challenging. Recent findings suggest that measures on embodiment are confounded by demand characteristics and suggestibility. To investigate the impact of demand characteristics on embodiment and presence, we compared results from an online experiment measuring participants' expectations, to the same experiment in virtual reality (VR). In the online experiment, participants watched a video of a participant performing the VR experiment. In the VR experiment, participants performed a soap-bubble-kicking task, which allowed the feelings of embodiment and presence to arise. We manipulated temporo-spatial movement synchrony (Movement: synchronous, asynchronous) and avatar visibility (Visibility: visible, invisible). In addition, we assessed participants' suggestibility with exercises. The introduced manipulations influenced the ratings in both experiments similarly. Embodiment ratings were additionally affected by suggestibility. Altogether, our results show that participants were aware of the research hypotheses, which indicates that demand characteristics confound embodiment and presence research alike. Overcoming challenges of demand characteristics is crucial to correctly interpret scientific results and to translate these results into applied settings.


Subject(s)
Virtual Reality , Humans , Movement
6.
J Physiol ; 600(10): 2429-2460, 2022 05.
Article in English | MEDLINE | ID: mdl-35389519

ABSTRACT

De novo missense variants in the KCNQ2 gene encoding the Kv7.2 subunit of voltage-gated potassium Kv7/M channels are the main cause of developmental and epileptic encephalopathy with neonatal onset. Although seizures usually resolve during development, cognitive/motor deficits persist. To gain a better understanding of the cellular mechanisms underlying network dysfunction and their progression over time, we investigated in vivo, using local field potential recordings of freely moving animals, and ex vivo in layers II/III and V of motor cortical slices, using patch-clamp recordings, the electrophysiological properties of pyramidal cells from a heterozygous knock-in mouse model carrying the Kv7.2 p.T274M pathogenic variant during neonatal, postweaning and juvenile developmental stages. We found that knock-in mice displayed spontaneous seizures preferentially at postweaning rather than at juvenile stages. At the cellular level, the variant led to a reduction in M ​​current density/conductance and to neuronal hyperexcitability. These alterations were observed during the neonatal period in pyramidal cells of layers II/III and during the postweaning stage in pyramidal cells of layer V. Moreover, there was an increase in the frequency of spontaneous network-driven events mediated by GABA receptors, suggesting that the excitability of interneurons was also increased. However, all these alterations were no longer observed in layers II/III and V of juvenile mice. Thus, our data indicate that the action of the variant is regulated developmentally. This raises the possibility that the age-related seizure remission observed in KCNQ2-related developmental and epileptic encephalopathy patients results from a time-limited alteration of Kv7 channel activity and neuronal excitability. KEY POINTS: The electrophysiological impact of the pathogenic c.821C>T mutation of the KCNQ2 gene (p.T274M variant in Kv7.2 subunit) related to developmental and epileptic encephalopathy has been analysed both in vivo and ex vivo in layers II/III and V of motor cortical slices from a knock-in mouse model during development at neonatal, postweaning and juvenile stages. M current density and conductance are decreased and the excitability of layer II/III pyramidal cells is increased in slices from neonatal and postweaning knock-in mice but not from juvenile knock-in mice. M current and excitability of layer V pyramidal cells are impacted in knock-in mice only at the postweaning stage. Spontaneous GABAergic network-driven events can be recorded until the postweaning stage, and their frequency is increased in layers II/III of the knock-in mice. Knock-in mice display spontaneous seizures preferentially at postweaning rather than at juvenile stages.


Subject(s)
Brain Diseases , KCNQ2 Potassium Channel , Seizures , Animals , Disease Models, Animal , Humans , KCNQ2 Potassium Channel/genetics , Mice , Nerve Tissue Proteins , Pyramidal Cells
7.
Eur Spine J ; 31(10): 2629-2638, 2022 10.
Article in English | MEDLINE | ID: mdl-35188587

ABSTRACT

BACKGROUND: Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. METHODS: Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. RESULTS: Models were developed and integrated into a web-app ( https://neurosurgery.shinyapps.io/fuseml/ ) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59-0.74], back pain (0.72, 95%CI: 0.64-0.79), and leg pain (0.64, 95%CI: 0.54-0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. CONCLUSIONS: Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk-benefit estimation, truly impacting clinical practice in the era of "personalized medicine" necessitates more robust tools in this patient population.


Subject(s)
Spinal Fusion , Back Pain/diagnosis , Back Pain/etiology , Back Pain/surgery , Female , Humans , Lumbar Vertebrae/surgery , Male , Middle Aged , Models, Statistical , Prognosis , Spinal Fusion/methods , Treatment Outcome
8.
Trials ; 23(1): 151, 2022 Feb 15.
Article in English | MEDLINE | ID: mdl-35168640

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is the second most deadly cancer affecting US adults and is also one of the most treatable cancers when detected at an earlier clinical stage of disease through screening. CRC health disparities experienced by African Americans are due in part to the later stage of diagnosis, suggesting the importance of improving African Americans' CRC screening participation. The national Screen to Save (S2S) initiative employs a community health educator to deliver CRC screening education which can be tailored for specific populations, and such approaches have increased CRC screening rates in disadvantaged and racial/ethnic minority populations. METHODS/DESIGN: In this trial emphasizing stool-based CRC screening, focus groups informed the development of an adapted S2S video and brochure tailored for African Americans and identified preferred motivational text messages for a multicomponent community health advisor (CHA) intervention. A CHA hired from the community was trained to deliver a 6-week CRC educational intervention consisting of an initial face-to-face meeting followed by 5 weeks of calls and texts. Interested eligible persons are enrolled primarily through recruitment by two partnering community health centers (CHCs) and secondarily through various outreach channels and, after consenting and completing a baseline survey, are randomly assigned to one of two study arms. The CHCs are blinded to study arm assignment. Intervention arm participants receive the brochure and CHA intervention while participants assigned to the control group receive only the brochure. All participants receive a stool-based CRC screening test from their health center, and the primary outcome is the completion of the screening test at 12 months. Secondary objectives are to estimate the effect of the intervention on mediating factors, explore the effect of moderating factors, and perform a cost-effectiveness analysis of the CHA intervention. DISCUSSION: The TUNE-UP study will enhance understanding about CRC screening in African Americans obtaining primary health care through CHCs and is one of the very few studies to examine a CHA intervention in this context. A better understanding of the mechanisms by which the intervention affects patient beliefs and behaviors will help focus future research while the exploratory cost-effectiveness analysis will inform CHCs' decision-making about implementing a CHA program to increase screening and reduce cancer health disparities. TRIAL REGISTRATION: ClinicalTrials.gov NCT04304001 . Registered on March 11, 2020.


Subject(s)
Black or African American , Colorectal Neoplasms , Adult , Colorectal Neoplasms/diagnosis , Early Detection of Cancer , Ethnicity , Humans , Minority Groups , Public Health , Randomized Controlled Trials as Topic , Safety-net Providers
9.
Support Care Cancer ; 30(4): 3495-3501, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35018521

ABSTRACT

PURPOSE: To determine the prevalence of memory problems in individuals with or without a history of DM and cancer and assess possible compounding effects of these diseases on self-reported memory problems (SRMP). METHODS: We used data from the 2009-2018 National Health and Nutrition Examination Survey. We conducted logistic regression analyses to determine the associations among DM, cancer, and SRMP, adjusting for age, sex, race/ethnicity, education, and poverty level. We examined the interaction effects of comorbid DM and cancer on SRMP. We compared participants with both DM and cancer to those with cancer only and to those with no DM or cancer. RESULTS: We included 26,842 adults ≥ 20 years old (N = 3374 with DM, N = 23,468 without DM) and 51.87% female. There were 10,434 Whites, 5730 Blacks, 6795 Hispanics, and 3883 other races/multiracial. More individuals with DM reported memory problems than those without DM (p < 0.0001). More individuals with cancer reported memory problems than those without cancer (p < 0.0001). Of those with both DM and cancer, 14.19% reported memory problems. More individuals with DM had cancer than those without DM (p < 0.0001). Of those with both diseases, 55.75% had DM before the cancer diagnosis. DM (odds ratio[OR] = 1.87, 95%CI, 1.55-2.26) and cancer (OR = 1.81, 95%CI, 1.43-2.30) predicted SRMP. The interaction between DM and cancer was significant, and the likelihood of having both diseases compared to having neither DM nor cancer was OR = 2.09, 95%CI, 1.41 - 3.11. CONCLUSION: Strategies to mitigate SRMP in individuals with comorbid DM and cancer history should consider the impact of both diseases.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes Mellitus , Neoplasms , Adult , Diabetes Mellitus/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Male , Neoplasms/epidemiology , Nutrition Surveys , Prevalence , Self Report , United States/epidemiology , Young Adult
10.
Neurosurg Rev ; 45(1): 517-524, 2022 Feb.
Article in English | MEDLINE | ID: mdl-33963469

ABSTRACT

Three-column osteotomy (3-CO) is a powerful technique in adult deformity surgery, and pedicle subtraction osteotomy (PSO) is the workhorse to correct severe kyphotic spinal deformities. Aging of the population, increasing cases of iatrogenic flat back deformities and understanding the importance of sagittal balance have led to a dramatic increase of this surgical technique. Surgery, however, is demanding and associated with high complication rates so that every step of the procedure requires meticulous technique. Particularly, osteotomy closure is associated with risks like secondary fracture, translation, or iatrogenic stenosis. This step is traditionally performed by compression or a cantilever maneuver with sometimes excessive forces on the screws or instrumentation. Implant loosening or abrupt subluxation resulting in construct failure and/or neurological deficits can result. The aim of this prospective registry study was to assess the efficacy and safety of our surgical PSO technique as well as the osteotomy closure by flexing a hinge-powered OR table. In a series of 84 consecutive lumbosacral 3-CO, a standardized surgical technique with special focus on closure of the osteotomy was prospectively evaluated. The surgical steps with the patients positioned prone on a soft frame are detailed. Osteotomy closure was achieved by remote controlled bending of a standard OR table without compressive or cantilever forces in all 84 cases. This technique carries a number of advantages, particularly the reversibility and the slow speed of closure with minimum force. There was not a single mechanical intraoperative complication such as vertebral body fracture, subluxation, or adjacent implant loosening during osteotomy closure, compared to external cohorts using the cantilever technique (p = 0.130). The feasibility of controlled 3-CO closure by flexing a standard OR table is demonstrated. This technique enables a safe, gentle closure of the osteotomy site with minimal risk of implant failure or accidental neurological injury.


Subject(s)
Kyphosis , Operating Tables , Spinal Fusion , Adult , Humans , Osteotomy , Prospective Studies , Retrospective Studies , Treatment Outcome
11.
Curr Top Behav Neurosci ; 55: 65-106, 2022.
Article in English | MEDLINE | ID: mdl-33454922

ABSTRACT

Epilepsy is commonly associated with cognitive and behavioral deficits that dramatically affect the quality of life of patients. In order to identify novel therapeutic strategies aimed at reducing these deficits, it is critical first to understand the mechanisms leading to cognitive impairments in epilepsy. Traditionally, seizures and epileptiform activity in addition to neuronal injury have been considered to be the most significant contributors to cognitive dysfunction. In this review we however highlight the role of a new mechanism: alterations of neuronal dynamics, i.e. the timing at which neurons and networks receive and process neural information. These alterations, caused by the underlying etiologies of epilepsy syndromes, are observed in both animal models and patients in the form of abnormal oscillation patterns in unit firing, local field potentials, and electroencephalogram (EEG). Evidence suggests that such mechanisms significantly contribute to cognitive impairment in epilepsy, independently of seizures and interictal epileptiform activity. Therefore, therapeutic strategies directly targeting neuronal dynamics rather than seizure reduction may significantly benefit the quality of life of patients.


Subject(s)
Cognitive Dysfunction , Epilepsy , Animals , Cognitive Dysfunction/etiology , Epilepsy/complications , Humans , Neurons/physiology , Quality of Life , Seizures/complications
12.
J Neurotrauma ; 39(9-10): 613-626, 2022 05.
Article in English | MEDLINE | ID: mdl-34937399

ABSTRACT

Sensorimotor function of patients with spinal cord injury (SCI) is commonly assessed according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). From the ISNCSCI segmental motor and sensory assessments, upper and lower extremity motor scores (UEMS and LEMS), sum scores of pinprick (PP) and light touch (LT) sensation, the neurological level of injury (NLI) and the classification of lesion severity according to the American Spinal Injury Association Impairment Scale (AIS) grade are derived. Changes of these parameters over time are used widely to evaluate neurological recovery. Evaluating recovery based on a single ISNCSCI scoring or classification variable, however, may misestimate overall recovery. Here, we propose an Integrated Neurological Change Score (INCS) based on the combination of normalized changes between two time points of UEMS, LEMS, and total PP and LT scores. To assess the agreement of INCS with clinical judgment of meaningfulness of neurological changes, changes of ISNCSCI variables between two time points of 88 patients from an independent cohort were rated by 20 clinical experts according to a five-categories Likert Scale. As for individual ISNCSCI variables, neurological change measured by INCS is associated with severity (AIS grade), age, and time since injury, but INCS better reflects clinical judgment about meaningfulness of neurological changes than individual ISNCSCI variables. In addition, INCS is related to changes in functional independence measured by the Spinal Cord Independence Measure (SCIM) in patients with tetraplegia. The INCS may be a useful measure of overall neurological change in clinical studies.


Subject(s)
Spinal Cord Injuries , Humans , Quadriplegia/complications , Recovery of Function , Sensation , Upper Extremity
13.
Intensive Care Med Exp ; 9(1): 47, 2021 Sep 17.
Article in English | MEDLINE | ID: mdl-34532776

ABSTRACT

BACKGROUND: There is a strong rationale for proposing transpulmonary pressure-guided protective ventilation in acute respiratory distress syndrome. The reference esophageal balloon catheter method requires complex in vivo calibration, expertise and specific material order. A simple, inexpensive, accurate and reproducible method of measuring esophageal pressure would greatly facilitate the measure of transpulmonary pressure to individualize protective ventilation in the intensive care unit. RESULTS: We propose an air-filled esophageal catheter method without balloon, using a disposable catheter that allows reproducible esophageal pressure measurements. We use a 49-cm-long 10 Fr thin suction catheter, positioned in the lower-third of the esophagus and connected to an air-filled disposable blood pressure transducer bound to the monitor and pressurized by an air-filled infusion bag. Only simple calibration by zeroing the transducer to atmospheric pressure and unit conversion from mmHg to cmH2O are required. We compared our method with the reference balloon catheter both ex vivo, using pressure chambers, and in vivo, in 15 consecutive mechanically ventilated patients. Esophageal-to-airway pressure change ratios during the dynamic occlusion test were close to one (1.03 ± 0.19 and 1.00 ± 0.16 in the controlled and assisted modes, respectively), validating the proper esophageal positioning. The Bland-Altman analysis revealed no bias of our method compared with the reference and good precision for inspiratory, expiratory and delta esophageal pressure measurements in both the controlled (largest bias -0.5 cmH2O [95% confidence interval: -0.9; -0.1] cmH2O; largest limits of agreement -3.5 to 2.5 cmH2O) and assisted modes (largest bias -0.3 [-2.6; 2.0] cmH2O). We observed a good repeatability (intra-observer, intraclass correlation coefficient, ICC: 0.89 [0.79; 0.96]) and reproducibility (inter-observer ICC: 0.89 [0.76; 0.96]) of esophageal measurements. The direct comparison with pleural pressure in two patients and spectral analysis by Fourier transform confirmed the reliability of the air-filled catheter-derived esophageal pressure as an accurate surrogate of pleural pressure. A calculator for transpulmonary pressures is available online. CONCLUSIONS: We propose a simple, minimally invasive, inexpensive and reproducible method for esophageal pressure monitoring with an air-filled esophageal catheter without balloon. It holds the promise of widespread bedside use of transpulmonary pressure-guided protective ventilation in ICU patients.

14.
Cancer Med ; 10(13): 4366-4374, 2021 07.
Article in English | MEDLINE | ID: mdl-34057299

ABSTRACT

BACKGROUND: While docetaxel/cisplatin/5-fluorouracil (DCF) outperforms CF in first-line gastric adenocarcinoma, toxicity remains an issue. METHODS: This multicenter phase II trial randomized chemonaïve metastatic gastric adenocarcinoma patients to fractionated weekly DCF (D 40 mg/m2 , C 35 mg/m², F 1800 mg/m² over 24 h, on days 1 and 8 every 3 weeks, arm (1) or fortnightly DCF (D 50 mg/m2 , C 50 mg/m², F 2000 mg/m² over 48 h every 2 weeks, arm (2). Prophylactic granulocyte colony-stimulating factor (G-CSF) was not allowed. The primary endpoint was the rate of febrile neutropenia within the first six treatment weeks (early FN). RESULTS: A total of 106 eligible patients were recruited. The early and overall FN rates were 9.5% and 17% in arm 1, respectively, and 5.9% and 8% in arm 2, respectively. Grade ≥3 toxicities occurred in 81% of patients in arm 1 and 90% of patients in arm 2, the most common being neutropenia (33% vs. 61%), fatigue (27% vs. 25%), vomiting (21% vs. 12%), anorexia (19% vs. 18%), and diarrhea (17% vs. 10%). Median progression-free survival and overall survival were 5.1 (95% CI, 3.2-6.5) and 8.2 months (95% CI, 6.0-14.5), respectively, in arm 1 and 5.2 (95% CI, 3.0-6.9) and 11.9 months (95% CI, 7.4-15.9), respectively, in arm 2. CONCLUSIONS: Fractionated weekly and fortnightly DCF regimens are associated with a low risk of early FN, and a better hematological toxicity profile as compared to historical DCF without compromising efficacy. Both regimens offer greater convenience removing the need for systematic use of prophylactic G-CSF.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Esophagogastric Junction , Stomach Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Anorexia/chemically induced , Anorexia/epidemiology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cisplatin/administration & dosage , Cisplatin/adverse effects , Diarrhea/chemically induced , Diarrhea/epidemiology , Docetaxel/administration & dosage , Docetaxel/adverse effects , Drug Administration Schedule , Fatigue/chemically induced , Fatigue/epidemiology , Febrile Neutropenia/epidemiology , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Granulocyte Colony-Stimulating Factor , Humans , Male , Middle Aged , Neutropenia/chemically induced , Neutropenia/epidemiology , Progression-Free Survival , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Vomiting/chemically induced , Vomiting/epidemiology
15.
Epilepsy Curr ; : 15357597211001877, 2021 Mar 16.
Article in English | MEDLINE | ID: mdl-33724060

ABSTRACT

The precise coordination of neuronal activity is critical for optimal brain function. When such coordination fails, this can lead to dire consequences. In this review, I will present evidence that in epilepsy, failed coordination leads not only to seizures but also to alterations of the rhythmical patterns observed in the electroencephalogram and cognitive deficits. Restoring the dynamic coordination of epileptic networks could therefore both improve seizures and cognitive outcomes.

16.
Acta Neurochir (Wien) ; 163(1): 275-280, 2021 01.
Article in English | MEDLINE | ID: mdl-33145630

ABSTRACT

BACKGROUND: Patients with intervertebral disc herniation undergo surgical removal of herniated disc material in cases of persisting symptoms and/or neurologic deficits. While motor deficits often prompt surgery, little is known about the optimal timing of surgery in these cases. The aim of this study was to prospectively evaluate the impact of timing of disc surgery on motor recovery. Does postponing surgical treatment worsen outcome? METHOD: In total, 120 patients with sciatica and/or sensorimotor deficits due to a lumbar disc herniation were surgically treated at the authors' center within a 3-month period. In 60 patients, motor deficits were present at the time of admission. Motor function was assessed using manual muscle testing and subdivided according to the Medical Research Council (MRC) scale. Patient demographics, neurologic deficits, duration of motor deficits, treatment characteristics, and outcome were assessed. At a minimum follow-up of 1 year, functional recovery and complications were collated. Patients were subdivided into groups according to the severity of the paresis (MRC ≤ 3/5 vs. MRC 4/5). Intra-group differences were compared based on the duration of the neurologic deficits. RESULTS: Patients with moderate and severe paresis (MRC ≤ 3/5) benefit from treatment within 72 h as they were shown to have a significantly higher complete recovery rate at 1-year follow-up (75% vs. 0%; p < 0.001). CONCLUSION: Immediate surgery should be offered to patients with moderate and severe motor deficits to increase the likelihood of neurologic recovery. This prospective data may have an impact on emergency triage in these patients.


Subject(s)
Diskectomy/methods , Intervertebral Disc Displacement/surgery , Lumbar Vertebrae/surgery , Postoperative Complications/epidemiology , Adult , Diskectomy/adverse effects , Female , Humans , Intervertebral Disc Displacement/pathology , Male , Middle Aged , Movement , Recovery of Function
17.
BMC Health Serv Res ; 20(1): 983, 2020 Oct 27.
Article in English | MEDLINE | ID: mdl-33109191

ABSTRACT

BACKGROUND: Patient satisfaction is a fundamental aspect of perceived health care quality. The original English version of the Patient Satisfaction with Cancer-related Care (PSCC) is a psychometrically validated, one-dimensional instrument with relevance to cancer-related care. The goal of the study was to perform a psychometric validation of the PSCC in German (PSCC-G). METHODS: A sample of 394 cancer patients were recruited at oncological clinics in Hamburg, Germany. Patients completed the PSCC-G, three subscales of the Patient Satisfaction and Quality in Oncological Care (PASQOC), and one subscale from the German version of the Recherché Evaluative sur la Performance des Réseaux de Santé (RESPERE-60) questionnaire. We conducted exploratory and confirmatory factor analyses (EFA and CFA) to determine the factorial validity, and we calculated Cronbach's coefficient alpha (α) to test the internal consistency of the PSCC-G. We examined the correlation between the PSCC-G and four subscales measuring additional dimensions of PS with care. We also conducted a multiple linear regression analysis to determine whether sociodemographics, self-perceived health status, and treatment setting predict scores on the PSCC-G. RESULTS: The EFA (using principal axis) revealed a one-factor solution. The Cronbach's α was 0.92. The convergent validity showed high correlations between three different subscales measuring patient satisfaction and the PSCC-G. Overall, males, older age patients, and those with a higher self-perceived health status were more satisfied with their cancer care based on their higher scores on the PSCC-G. CONCLUSION: The PSCC-G is a reliable and valid instrument that can assess satisfaction with cancer-related care for German-speaking cancer patients.


Subject(s)
Neoplasms , Patient Satisfaction , Psychometrics , Quality of Health Care , Surveys and Questionnaires/standards , Adult , Aged , Factor Analysis, Statistical , Female , Germany , Humans , Male , Middle Aged , Neoplasms/therapy , Reproducibility of Results
18.
Acta Neurochir (Wien) ; 162(11): 2927-2931, 2020 11.
Article in English | MEDLINE | ID: mdl-32808086

ABSTRACT

Monostotic fibrous dysplasia (MFD) of the lumbar spine represents an exceedingly rare lesion. A 26-year-old patient presented with a progressive osteolytic lesion of the vertebral body L2 and the diagnosis of MFD. A minimally invasive left-sided eXtreme Lateral Interbody Fusion (XLIF) approach with resection of the vertebral body L2 with placement of a mesh cage was performed. No complications were observed perioperatively and the symptoms rapidly improved. Minimally invasive piecemeal resection with a combined dorsolateral approach showed a favorable clinical and radiological outcome and seems to be a safe and reliable technique for MFD.


Subject(s)
Fibrous Dysplasia, Monostotic/surgery , Kyphosis/surgery , Spinal Fusion/methods , Adult , Fibrous Dysplasia, Monostotic/complications , Humans , Kyphosis/etiology , Lumbar Vertebrae/surgery , Male
19.
Cereb Cortex ; 30(9): 5049-5066, 2020 07 30.
Article in English | MEDLINE | ID: mdl-32377688

ABSTRACT

Alterations in the voltage-gated sodium channel Nav.1.1 are implicated in various neurological disorders, including epilepsy, Alzheimer's disease, and autism spectrum disorders. Previous studies suggest that the reduction of Nav1.1 expression leads to a decrease of fast spiking activity in inhibitory neurons. Because interneurons (INs) play a critical role in the temporal organization of neuronal discharge, we hypothesize that Nav1.1 dysfunction will negatively impact neuronal coordination in vivo. Using shRNA interference, we induced a focal Nav1.1 knock-down (KD) in the dorsal region of the right hippocampus of adult rats. Focal, unilateral Nav1.1 KD decreases the performance in a spatial novelty recognition task and the firing rate in INs, but not in pyramidal cells. It reduced theta/gamma coupling of hippocampal oscillations and induced a shift in pyramidal cell theta phase preference. Nav1.1 KD degraded spatial accuracy and temporal coding properties of place cells, such as theta phase precession and compression of ongoing sequences. Aken together, these data demonstrate that a deficit in Nav1.1 alters the temporal coordination of neuronal firing in CA1 and impairs behaviors that rely on the integrity of this network. They highlight the potential contribution of local inhibition in neuronal coordination and its impact on behavior in pathological conditions.


Subject(s)
Hippocampus/physiology , NAV1.1 Voltage-Gated Sodium Channel/genetics , Place Cells/physiology , Spatial Behavior/physiology , Animals , Gene Knockdown Techniques , Male , Rats , Rats, Long-Evans
20.
World Neurosurg ; 140: 664-673, 2020 08.
Article in English | MEDLINE | ID: mdl-32445895

ABSTRACT

BACKGROUND: The desire to improve accuracy and safety and to favor minimally invasive techniques has given rise to spinal robotic surgery, which has seen a steady increase in utilization in the past 2 decades. However, spinal surgery encompasses a large spectrum of operative techniques, and robotic surgery currently remains confined to assistance with the trajectory of pedicle screw insertion, which has been shown to be accurate and safe based on class II and III evidence. The role of robotics in improving surgical outcomes in spinal pathologies is less clear, however. METHODS: This comprehensive review of the literature addresses the role of robotics in surgical outcomes in spinal pathologies with a focus on the various meta-analysis and prospective randomized trials published within the past 10 years in the field. RESULTS: It appears that robotic spinal surgery might be useful for increasing accuracy and safety in spinal instrumentation and allows for a reduction in surgical time and radiation exposure for the patient, medical staff, and operator. CONCLUSION: Robotic assisted surgery may thus open the door to minimally invasive surgery with greater security and confidence. In addition, the use of robotics facilitates tireless repeated movements with higher precision compared with humans. Nevertheless, it is clear that further studies are now necessary to demonstrate the role of this modern tool in cost-effectiveness and in improving clinical outcomes, such as reoperation rates for screw malpositioning.


Subject(s)
Robotic Surgical Procedures/instrumentation , Robotic Surgical Procedures/trends , Spinal Diseases/surgery , Surgery, Computer-Assisted/instrumentation , Surgery, Computer-Assisted/trends , Fluoroscopy/instrumentation , Fluoroscopy/trends , Humans , Intraoperative Neurophysiological Monitoring/instrumentation , Intraoperative Neurophysiological Monitoring/trends , Minimally Invasive Surgical Procedures/instrumentation , Minimally Invasive Surgical Procedures/trends , Randomized Controlled Trials as Topic/methods , Spinal Diseases/diagnostic imaging , Treatment Outcome
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