Different composition of leucocytes in cortical and cancellous bone healing in a mouse model.

OBJECTIVES: Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline. METHODS: Ten-week-old male C56/Bl6J mice were randomized to either cancellous injury in the proximal tibia or cortical injury in the femoral diaphysis. Regenerating tissues were analyzed with flow cytometry at days 3 and 5, using panels with 15 antibodies for common macrophage and lymphocyte markers. The cellular response from day 3 to 5 was compared in order to identify differences in how cancellous and cortical bone healing develop. RESULTS: Between day 3 and 5, the granulocytes increased in the cancellous model, whereas the lymphocytes (T cells, B cells, NK cells) and monocytes (CD11b+, F4/80+, CD206+, CD14+) increased in the cortical model. CONCLUSION: These results suggest an acute type of inflammation in cancellous bone healing, and a more chronic inflammation in cortical healing. This might explain, in part, why cancellous healing is faster and more resistant to anti-inflammatory drugs than are diaphyseal fractures.Cite this article: L. Tätting, O. Sandberg, M. Bernhardsson, J. Ernerudh, P. Aspenberg. Different composition of leucocytes in cortical and cancellous bone healing in a mouse model. Bone Joint Res 2018;7:620-628. DOI: 10.1302/2046-3758.712.BJR-2017-0366.R2.

Glucocorticoids inhibit shaft fracture healing but not metaphyseal bone regeneration under stable mechanical conditions.

OBJECTIVES: Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors. METHODS: We investigated the role of inflammation in three different models: a metaphyseal screw pull-out, a shaft fracture with unstable nailing (IM-nail) and a stable external fixation (ExFix) model. For each, half of the animals received dexamethasone to reduce inflammation, and half received control injections. Mechanical and morphometric evaluation was used. RESULTS: As expected, dexamethasone had a strong inhibitory effect on the healing of unstable, but also stable, shaft fractures. In contrast, dexamethasone tended to increase the mechanical strength of metaphyseal bone regenerated under stable conditions. CONCLUSIONS: It seems that dexamethasone has different effects on metaphyseal and diaphyseal bone healing. This could be explained by the different role of inflammation at different sites of injury. Cite this article: Bone Joint Res 2015;4:170-175.

Effect of local vs. systemic bisphosphonate delivery on dental implant fixation in a model of osteonecrosis of the jaw.

Locally applied bisphosphonates may improve the fixation of metal implants in bone. However, systemic bisphosphonate treatment is associated with a risk of osteonecrosis of the jaw (ONJ). We hypothesized that local delivery of bisphosphonate from the implant surface improves the fixation of dental implants without complications in a setting where systemic treatment induces ONJ. Forty rats were randomly allocated to 4 groups of 10. All groups received a titanium implant inserted in an extraction socket. Group I received the implants only. Group II received dexamethasone (0.5 mg/kg). Group III received dexamethasone as above plus alendronate (200 µg/kg). Group IV received zoledronate-coated implants and dexamethasone as above. The animals were sacrificed 2 weeks after tooth extraction. All 10 animals with systemic alendronate treatment developed large ONJ-like changes, while all with local treatment were completely healed. Implant removal torque was higher for the bisphosphonate-coated implants compared with the other groups (p < 0.03 for each comparison). Micro-computed tomography of the maxilla showed more bone loss in the systemic alendronate group compared with groups receiving local treatment (p = 0.001). Local bisphosphonate treatment appears to improve implant fixation in a setting where systemic treatment caused ONJ.

Nasal continuous positive airway pressure in stroke patients with sleep apnoea: a randomized treatment study.

The authors have investigated whether treatment of sleep apnoea with nasal continuous positive airway pressure (nCPAP) improves depressive symptoms, personal activities of daily living (ADL), cognitive functioning and delirium in patients that have suffered a stroke. Sixty-three patients consecutively admitted to a stroke rehabilitation unit 2-4 weeks after a stroke, with an apnoea/hypopnoea index > or =15, were randomized to either nCPAP treatment (n=33) or a control group (n=30). Four patients dropped out after randomization. Both groups were assessed at baseline and after 7 and 28 nights using the Montgomery-Asberg Depression Rating Scale (MADRS), Barthel-ADL index, and the Mini-Mental State Examination (MMSE) scale. Compared to the control group, depressive symptoms (MADRS total score) improved in patients randomized to nCPAP treatment (p=0.004). No significant treatment effect was found with regard to delirium, MMSE or Barthel-ADL index. Delirium and low cognitive level (MMSE score) explained poor compliance with nCPAP. Depressive symptoms are reduced through nasal continuous positive airway pressure treatment in patients with severe stroke and sleep apnoea. Compliance with nasal continuous positive airway pressure treatment is a problem in stroke patients, especially when delirium and severe cognitive impairment occur.

Sleep apnea, delirium, depressed mood, cognition, and ADL ability after stroke.

OBJECTIVES: The incidence of sleep apnea and stroke increases with age. The aim of this study was to investigate the presence of sleep apnea after stroke and its relationship to delirium, depressed mood, cognitive functioning, ability to perform activities of daily living (ADLs), and psychiatric and behavior symptoms. DESIGN: Cross-sectional study. SETTING: Geriatric stroke rehabilitation unit. PARTICIPANTS: 133 patients (78 women and 55 men, mean age 77.1 +/- 7.7 years) consecutively admitted to a geriatric stroke rehabilitation unit. MEASUREMENTS: All patients underwent overnight respiratory sleep recordings at 23 +/- 7 days (range 11 to 41 days) after suffering a stroke. The patients were assessed using the Organic Brain Syndrome Scale, Montgomery-Asberg-Depression-Rating Scale, Mini-Mental State Examination (MMSE), and Barthel-ADL Index. Sleep apnea was defined as an apnea-hypopnea index (AHI) of 10 or more. RESULTS: The median of the AHI for the studied sample (N = 133) was 13 (range 0-79; interquartile range 6-28). Fifty-nine percent fulfilled the criteria for sleep apnea; 52% with first-ever stroke had sleep apnea. More patients with sleep apnea than without were delirious, depressed, or more ADL-dependent. Sleep apnea patients also had a higher frequency of ischemic heart disease and had more often suffered from an earlier cerebral infarction. Multivariate analysis showed that obesity, low ADL scores, ischemic heart disease, and depressed mood were independently associated with sleep apnea. Low ADL scores, apnea-related hypoxemia, body mass index < or = 27, and impaired vision were independently associated with delirium. The presence of sleep apnea was not associated with any specific type of stroke or location of the brain lesion. CONCLUSIONS: Sleep apnea is common in stroke patients and is associated with delirium, depressed mood, latency in reaction and in response to verbal stimuli, and impaired ADL ability. We suggest a trial investigating whether delirium, depressed mood, and ADL ability improve with nasal continuous positive airway pressure treatment of sleep apnea in stroke patients.

Clinical profile of delirium in older patients.

OBJECTIVE: To examine the prevalence, psychiatric and behavior symptoms, differing symptom profiles, and diurnal variations of delirium in older patients. DESIGN: A descriptive, point prevalence study with a cross-sectional design. SETTING: One ordinary county hospital (n = 148), three nursing homes (n = 202), five old people's homes (n = 196), and home medical care patients (n = 171) in parts of a hospital catchment area in Mid-Sweden. PARTICIPANTS: A total of 717 patients 75 years of age and older were observed and assessed for the prevalence of delirium. Women accounted for 66.4% of the studied population, and the mean age for both sexes was 83.7 years. MEASUREMENTS: All patients were examined using the OBS (Organic Brain Syndrome) scale, and delirium was diagnosed according to DSM-III-R. RESULTS: Delirium was diagnosed in 315 of 717 (43.9%) patients, and 135 of 315 (42.9%) of the delirious patients had dementia. Thirty-seven percent of the patients with delirium were delirious in the afternoon, evening, or at night, and 47% of the delirious patients had morning delirium. The delirious patients presented a wide variety of psychiatric symptoms. More than half the patients exhibiting anxiety, psychomotor slowing, depressed mood, and irritability. Nearly 26% were classified as having hypoactive, 22% as having hyperactive, and 42% as having mixed delirium, whereas 11% had neither hypo- nor hyperactive delirium. Seventy-seven percent were classified as having delirium with pronounced emotional and 43% with pronounced psychotic symptoms. CONCLUSIONS: This study shows that patients with delirium have very different clinical profiles. This might indicate a need for different treatment strategies for patients with different types of delirium.

Epidemiology of delirium.

Delirium is one of the most frequent symptoms of disease in the elderly. A large variation of incidence and prevalence data is reported probably due to different patient populations and inconsistent diagnostic criteria. In medical and surgical elderly inpatients recent studies report a prevalence rate of approximately 15% and in postoperative patients the incidence and prevalence rates vary greatly, 7-52%, depending on patient population and clinical setting. In nursing homes the prevalence is even higher and delirium is often combined with dementia. Data supports the statement that delirium is most often found in hospitalized somatically ill elderly patients. As a consequence of the rising number of elderly in hospitals we have to expect an increase in the prevalence and incidence of delirium.

Prevalence of dementia, delirium and psychiatric symptoms in various care settings for the elderly.

A prevalence study of psychiatric symptoms was performed in parts of a hospital catchment area in Mid-Sweden. In total 717 patients, aged 75 years and above, who were receiving care in an emergency hospital, three nursing homes, five old people's homes and two home medical care districts were included. All patients were examined using the OBS-scale (Organic Brain Syndrome Scale). Anxiety (51%), psychomotor slowing (45%), delirium (44%), depressed mood (41%), irritability (40%) and dementia (33%) were the most prevalent psychiatric symptoms or diagnoses in the sample but there were wide differences between the four care settings. The present study shows that the prevalence of dementia, delirium and psychiatric symptoms is high in all types of care settings for the elderly. It also demonstrates the need for psychiatric medical and nursing competence in all types of care for the elderly.