Early symptoms in the prodromal phase of delirium: a prospective cohort study in elderly patients undergoing hip surgery.

OBJECTIVES: The authors investigated prodromal delirium symptoms in elderly patients undergoing hip surgery. METHODS: This was a prospective cohort study in the setting of a large medical school-affiliated general hospital in Alkmaar, The Netherlands. Participants were patients undergoing hip surgery aged 70 and older at risk for delirium. Before surgery, patients were randomized to low-dose prophylactic haloperidol treatment or placebo. Daily assessments were based on patient interviews with the Mini-Mental State Examination and Digit Span test. The Delirium Rating Scale-Revised (DRS-R-98) was used to measure early symptoms during the prodromal phase before the onset of delirium. RESULTS: Data of 66 patients with delirium were compared with those of 35 at-risk patients who did not develop delirium: 14 of 66 patients (21%) had delirium on the day of surgery or early the day after, 32 of 66 (48%) on the second day, 14 of 66 on the third, and six of 66 (9%) on the fourth. The average DRS-R-98 total scores on day -4 to day -1 before delirium were 1.9 for the comparison group patients and 5.0, 4.3, 5.8, and 10.7 for patients with postoperative delirium. Multivariate analysis showed that the early symptoms memory impairments, incoherence, disorientation, and underlying somatic illness predict delirium. CONCLUSIONS: Most elderly patients undergoing hip surgery with postoperative delirium already have early symptoms in the prodromal phase of delirium. These findings are potentially useful for screening purposes and for optimizing prevention strategies targeted at reducing the incidence of postoperative delirium.     

A slim needle-shaped multiwire microelectrode for intracerebral recording

The construction of a needle-shaped multiwire microelectrode is described. It can be made with simple mechanical tools. The presented electrode assembly consists of 12 insulated nichrome wires (core diameter 25 μm) which are embedded in epoxylite resin. The straight-cut wire tips are aligned lengthwise and have a relative spacing of 150 μm. Outer dimensions vary from 100 × 180 μm at the level of the 1st electrode channel, to 100 × 100 μm at the level of the 12th channel at the tip. The configuration of this electrode was determined by its application: the laminar analysis of evoked potentials in the cortex of the rat. However, the number of channels, the diameter of the (nichrome) wire which determines the surface area of these channels, and the channel spacing can be easily adjusted during construction to meet other experimental requirements, such as the recording of single-unit activity. The electrode which is composed of biocompatible materials is suited for the study of field potentials and multiple-unit activity, in both acute and chronic experiments, and can be used repeatedly. To demonstrate the performance of the electrode assembly, a depth profile of field potentials is presented, accompanied by the corresponding current source density distribution. The potentials were recorded in the somatosensory cortex of the rat following stimulation of the median nerve under ketamine anesthesia.     

Identification of two proteins associated with virulence of Streptococcus suis type 2.

The protein profiles of various cell fractions of 180 strains of Streptococcus suis type 2, which were isolated from diseased pigs, from healthy pigs when they were slaughtered, and from human patients, were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The isolates from diseased pigs contained two proteins that were absent in most of the isolates from healthy pigs. One of these proteins was a 136-kDa protein that was previously identified as the muramidase-released protein (MRP). This protein was predominantly detected in protoplast supernatants and culture supernatants. The second protein was a 110-kDa protein that was detected only in culture supernatants and therefore was provisionally called extracellular factor (EF). Three phenotypes of S. suis type 2 strains were recognized. Isolates from organs of diseased pigs mainly belonged to the MRP+ EF+ phenotype (77%), while isolates from tonsils of healthy pigs mainly had the MRP- EF- phenotype (86%). Most of the isolates from human patients contained MRP (89%); 74% had the MRP+ EF- phenotype. These findings confirm the results of previous investigations which demonstrated that S. suis type 2 strains differ in virulence. Monoclonal antibodies raised against the 110-kDa EF recognized proteins with higher molecular weights in culture supernatants of all of the strains with the MRP+ EF- phenotype. However, none of the strains with the MRP+ EF+ phenotype produced these high-molecular-weight proteins. Our results demonstrate that MRP and EF are associated with virulence. This suggests that one or both of these proteins are virulence factors that play a role in the pathogenesis of S. suis type 2 infections in pigs and human patients.     

Structural brain abnormalities in patients with schizophrenia and their healthy siblings

OBJECTIVE: The authors sought to investigate the contribution of genotype on structural brain abnormalities in schizophrenia. METHOD: Intracranial volumes and volumes of the cerebrum, white and gray matter, lateral and third ventricles, frontal lobes, caudate nucleus, amygdala, hippocampus, parahippocampal gyrus, and the cerebellum were measured in 32 same-sex siblings discordant for schizophrenia and 32 matched comparison subjects by means of magnetic resonance imaging. RESULTS: Third ventricle volumes did not differ between the schizophrenic patients and their healthy siblings. However, both had higher third ventricle volumes than did the comparison subjects. The schizophrenic patients had lower cerebrum volumes than did the comparison subjects, whereas the cerebrum volume of the healthy siblings did not significantly differ from the patients or comparison subjects. Additionally, patients with schizophrenia displayed a volume reduction of the frontal lobe gray matter and a volume increase of the caudate nuclei and lateral ventricles compared to both their healthy siblings and comparison subjects. Intracranial volume, CSF volume, or volumes of the cerebellum, amygdala, hippocampus, or the parahippocampal gyrus did not significantly differ among the patients, siblings, and comparison subjects. CONCLUSIONS: Healthy siblings share third ventricle enlargement with their affected relatives and may partially display a reduction in cerebral volume. These findings suggest that third ventricular enlargement, and to some extent cerebral volume decrease, may be related to genetic defects that produce a susceptibility to schizophrenia.     

Thallium-201 single-photon emission computed tomography as an early predictor of outcome in recurrent glioma.

PURPOSE: With limited response rates and potential toxicity of chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. Currently, the assessment of treatment response in glioma patients is based on the combination of radiologic and clinical findings. However, response monitoring with computed tomography (CT) or magnetic resonance imaging (MRI) is hampered by several pitfalls and is prone to interobserver variability. The aim of this study was to establish the value of thallium-201 single-photon emission computed tomography (201Tl-SPECT) as a predictor of overall survival and response to chemotherapy in recurrent glioma, and to compare the value of 201Tl-SPECT with that of CT and MRI. PATIENTS AND METHODS: We studied patients who underwent CT or MRI and 201Tl-SPECT before chemotherapy (n = 57), and patients who also had undergone CT or MRI and 201Tl-SPECT after two courses of chemotherapy (n = 44). The value of the radiologic variables (CT-MRI tumor size, 201Tl-SPECT tumor size, and maximal tumor intensity) at baseline and at follow-up in predicting overall survival, and the percentage of patients alive and progression-free at 6 months (APF6) were examined using Cox regression and logistic regression analysis. RESULTS: Both at baseline and at follow-up, 201Tl-SPECT maximal tumor intensity was the strongest predictive variable and was inversely related to overall survival and APF6. In particular, progression of maximal tumor intensity after two courses of chemotherapy was a powerful predictor of poor outcome. CONCLUSION: 201Tl-SPECT is superior to conventional CT-MRI in the early prediction of overall survival and response to chemotherapy in patients with recurrent glioma.     

Traumatic Brain Injury in Patients Receiving Direct Oral Anticoagulants

BackgroundEmergency departments (EDs) are faced with a growing number of patients with traumatic brain injury (TBI) using direct oral anticoagulants (DOACs). However, there remains uncertainty about the bleeding risk, rate of hematoma expansion, and the efficacy of reversal strategies in these patients.ObjectiveThis study aims to identify the risk of traumatic hemorrhagic complications in patients with TBI using DOACs.MethodsIn this retrospective study we included patients with TBI. All TBI patients were using DOACs, attended one of the three EDs of our hospital between January 2016 and October 2019, and received a computed tomography (CT) scan of the brain. The primary outcome was any traumatic intracranial hemorrhage on CT. Secondary outcomes were the use of reversal agents, secondary neurological deterioration, a neurosurgical intervention within 30 days after the injury, length of stay (LOS), Glasgow Outcome Scale (GOS) at discharge, and mortality.ResultsOf the included patients (N = 316), 24 patients (7.6%, 95% confidence interval [CI] 4.2–9.8) presented with a traumatic intracranial hematoma (ICH). Seven patients (2.2%, 95% CI 0.6–3.8) received a reversal agent and 1 patient (0.3%, 95% CI ?0.3–0.9) underwent a neurosurgical intervention. Of the 24 patients with a traumatic ICH, progression of the lesion was seen in 6 patients (1.9%, 95% CI 0.4–3.4). The mean LOS was 6.5 days (95% CI 3.0–10.1) and the mean GOS at discharge was 4 (95% CI 3.6–4.6). Death occurred in 1 patient (0.3%, 95% CI ?0.3–0.9) suffering from an ICH.ConclusionBased on the present findings it can be postulated that TBI patients using DOACs have a low risk for ICH. Hematoma progression occurred, however, in a substantial number of patients. Considering the retrospective nature of the present study, future prospective trials are needed to confirm this finding.     

IL-13 genetic polymorphism identifies children with late wheezing after respiratory syncytial virus infection

BACKGROUND: The nature of wheezing after respiratory syncytial virus lower respiratory tract infection (RSV LRTI) is usually transient. However, some children will develop persistent or late wheezing. OBJECTIVE: We hypothesized that early and late postbronchiolitis wheezing are determined by distinct clinical, immunologic, and genetic variables. METHODS: A cohort of 101 children hospitalized for RSV LRTI was prospectively followed for 6 years. During RSV LRTI, cytokine studies were performed and genetic polymorphisms were determined. Parents performed daily log registration of respiratory symptoms during the first 3 years of follow-up and again at age 6 years during the winter season. RESULTS: Distinctive associations for early and late postbronchiolitis wheezing were found. We previously showed that airflow limitation during RSV LRTI as well as convalescent monocyte IL-10 production are associated with early wheezing. These variables were not associated with late wheezing. On the other hand, atopic family history was not associated with early wheezing, but it was associated with late wheezing. Most importantly, the IL-13 Gln allele was associated with late wheezing (odds ratio 3.27, 95% confidence interval 1.32-8.06), but it was not associated with early wheezing. CONCLUSION: This study revealed distinct clinical, immunologic, and genetic determinants of early and late wheezing after RSV LRTI, indicating distinct pathophysiological mechanisms. We conclude that late wheezing at age 6 years, but not early postbronchiolitis wheezing, is an asthmatic phenomenon and genetically related to a functional IL-13 polymorphism. CLINICAL IMPLICATIONS: After RSV LRTI, wheezing at age 6 years is not related to early postbronchiolitis wheezing and represents a distinct disease entity.     

The importance of the disease process and disease‐modifying antirheumatic drug treatment in the development of septic arthritis in patients with rheumatoid arthritis

Objective

To evaluate the effect of disease‐modifying antirheumatic drugs (DMARDs) on the likelihood of patients with rheumatoid arthritis (RA) developing septic arthritis (SA).

Methods

The United Kingdom General Practice Research Database (GPRD) was used to identify adults with RA, and age‐, sex‐, and practice‐matched control subjects. Subjects were studied between 1987 and 2002. The risk of developing SA (excluding infected joint replacements) for individuals with RA was calculated and the effect of DMARD use determined.

Results

A total of 136,977 subjects (34,250 patients with RA, 102,747 controls) were identified. SA was identified in 345 subjects, of which 321 (236 in patients with RA, 85 in controls) cases occurred during the study period. The incidence rate of SA was 12.9 times higher in subjects with RA than in those without (95% confidence interval [95% CI] 10.1–16.5, P < 0.001). The incident rate ratios (IRRs) for developing SA while receiving DMARDs compared with receiving no DMARDs were different for different medications. Penicillamine (adjusted IRR 2.51, 95% CI 1.29–4.89, P = 0.004), sulfasalazine (adjusted IRR 1.74, 95% CI 1.04–2.91, P = 0.03), and prednisolone (adjusted IRR 2.94, 95% CI 1.93–4.46, P < 0.001) were associated with an increased incidence of SA when compared with not receiving any DMARD. The use of other DMARDs including methotrexate showed no such effect.

Conclusion

Individuals with RA have an increased risk of developing SA. This increased risk can be attributed to both the disease process and the use of DMARDs.