[Application and value of intravascular ultrasound for excimer laser ablation combined with drug-coated balloon in the treatment of lower limb arteriosclerotic obliterans].

Objective: To examine the value of intravascular ultrasound (IVUS) for excimer laser ablation (ELA) combined with drug-coated balloon (DCB) in treating lower limb arteriosclerotic obliterans (ASO). Methods: As a prospective case series study, patients who underwent ELA combined with DCB for lower limb ASO with the guidance of IVUS from September 2021 to March 2022 at Department of Vascular Surgery, Zhongshan Hospital, Fudan University were enrolled prospectively. Lesion characteristics, procedure-related outcomes and complications were collected. The therapy outcomes were compared with baseline data by paired t test. Results: There were 8 males and 2 females, aged (72.0±5.9) years (range: 61 to 81 years). Of all the 11 lesions, there were 8 lesions in superficial femoral artery and 3 in popliteal artery. The lesion length was (7.0±2.4) cm (range: 3.2 to 9.8 cm). There were 4 chronic totally occlusion and 7 severe stenosis. All patients underwent the operation successfully. The technical success rate was 10/11. Bailout stenting was performed in one lesion because of flow-limiting dissection. Four lesions were grade 3 to 4 in peripheral artery calcium score system, and 9 lesions with calcification arc≥180°. Larger diameter drug-coated balloons were selected in 5 lesions after measurement of intravascular ultrasound. The follow-up time was (6.0±1.9) months (range: 3 to 9 months). The ankle-brachial index of the patient was significantly improved immediately after surgery (0.97±0.13 vs. 0.48±0.18, t=-7.60, P<0.01) and at 3 months after surgery (0.95±0.12 vs. 0.48±0.18, t=-7.17, P<0.01). The 3-month primary patency rate was 11/11, the target lesion reintervention was 0 and ulcer healing rate was 3/4. Conclusion: IVUS assisted ELA in the treatment of lower limb artery lesions is safe and effective in early stage.

[Application value of excimer laser ablation combined with drug-coated balloon in non-stent atherosclerotic lesions of lower extremity arteries].

Objective: To examine the effect of excimer laser ablation (ELA) combining with drug-coated balloon (DCB) for atherosclerotic lesions in no-stenting zones (NSZ) of the lower extremity. Methods: From June 2019 to December 2021, 46 patients who underwent ELA combining with DCB in lesions of NSZ at Zhongshan Hospital, Fudan University and Jinshan Hospital, Fudan University were retrospectively enrolled, including 29 males and 17 females. The age was (72.5±11.7) years (range: 42 to 93 years). Among them, 44 lesions (95.7%, 44/46) were in popliteal artery and 2 lesions (4.3%, 2/46) were in common femoral artery. Chronic total occlusion (CTO) was observed in 31 patients (76.4%, 31/46), and stenotic lesions were observed in 15 patients (32.6%, 15/46). The length of lesions was (7.3±2.7) cm (range: 3.0 to 13.2 cm). Patients were followed at 6, 12 months after surgery and every year thereafter, and they underwent Doppler and CT angiography examination at each follow-up point. The primary endpoint was primary patency. The secondary endpoints included major amputation-free survival (MAFS) rate, technical success, bailout stent, ankle-brachial index (ABI), target lesion reintervention (TLR). Student t test was applied to compare the difference between ABI of 6 or 12 months after surgery and the baseline. Primary patency, freedom from TLR, and MAFS rate were calculated by Kaplan-Meier method. Results: The technical success rate was 91.3% (42/46). The rate of procedure-related complication was 6.5% (3/46), and all the complications were distal embolization. The rate of flow-limiting dissection was 8.7% (4/46). ABI was significantly increased at 6 and 12 months compared to preoperatively (0.90±0.10 vs. 0.42±0.10, t=-4.48, P<0.01; 0.87±0.12 vs. 0.42±0.10, t=-5.21, P<0.01). The follow-up time[M(IQR)] was 22.5 (8.8) months (range: 6 to 32 months). TLR was performed in 4 patients (4/46, 8.7%). The 2-year primary patency was 86.2% (95%CI: 71.8% to 93.5%). The 2-year freedom from TLR and MAFS rate were 90.7% (95%CI: 77.0% to 96.4%) and 97.8% (95%CI: 85.6% to 99.7%), respectively. Conclusion: ELA combining with DCB can be applied to treat atherosclerotic lesions in NSZ.

Quantification of bone marrow interstitial pH and calcium concentration by intravital ratiometric imaging.

The fate of hematopoietic stem cells (HSCs) can be directed by microenvironmental factors including extracellular calcium ion concentration ([Ca2+]e), but the local [Ca2+]e around individual HSCs in vivo remains unknown. Here we develop intravital ratiometric analyses to quantify the absolute pH and [Ca2+]e in the mouse calvarial bone marrow, taking into account the pH sensitivity of the calcium probe and the wavelength-dependent optical loss through bone. Unexpectedly, the mean [Ca2+]e in the bone marrow (1.0 ± 0.54 mM) is not significantly different from the blood serum, but the HSCs are found in locations with elevated local [Ca2+]e (1.5 ± 0.57 mM). With aging, a significant increase in [Ca2+]e is found in M-type cavities that exclusively support clonal expansion of activated HSCs. This work thus establishes a tool to investigate [Ca2+]e and pH in the HSC niche with high spatial resolution and can be broadly applied to other tissue types.

Physio-Cognitive Decline Syndrome as the Phenotype and Treatment Target of Unhealthy Aging.

In this era of unprecedented longevity, healthy aging is an important public health priority. Avoiding or shortening the period of disability or dementia before death is critical to achieving the defining objectives of healthy aging, namely to develop and maintain functional capabilities that enable wellbeing in older age. The first step is to identify people who are at risk and then to implement effective primary interventions. Geriatricians have identified a distinct clinical phenotype of concurrent physical frailty and cognitive impairment, which predicts high risk of incident dementia and disability and is potentially reversible. Differing operational definitions for this phenotype include "cognitive frailty", "motoric cognitive risk syndrome" and the recently proposed "physio-cognitive decline syndrome (PCDS)". PCDS is defined as concurrent mobility impairment no disability (MIND: slow gait or/and weak handgrip) and cognitive impairment no dementia (CIND: ≥1.5 SD below the mean for age-, sex-, and education-matched norms in any cognitive domain but without dementia). By these criteria, PCDS has a prevalence of 10-15% among community-dwelling older persons without dementia or disability, who are at increased risk for incident disability (HR 3.9, 95% CI 3.0-5.1), incident dementia (HR 3.4, 95% CI 2.4-5.0) and all-cause mortality (HR 6.7, 95% CI 1.8-26.1). Moreover, PCDS is associated with characteristic neuroanatomic changes in the cerebellum and hippocampus, and their neurocircuitry, which are distinct from neuroimaging features in normal aging and common dementia syndromes. Basic research and longitudinal clinical studies also implicate a hypothetical muscle-brain axis in the pathoetiology of PCDS. Most important, community-dwelling elders with PCDS who participated in a multidomain intervention had significant improvements in global cognitive function, and especially in the subdomains of naming and concentration. Our proposed operational definition of PCDS successfully identifies an appreciable population of at-risk older people, establishes a distinct phenotype with an apparently unique pathoetiology, and is potentially reversible. We now need further studies to elucidate the pathophysiology of PCDS, to validate neuroimaging features and muscle-secreted microRNA biomarkers, and to evaluate the effectiveness of sustained multidomain interventions.

[Debulking strategy of endovascular treatment for lower extremity artery lesions].

Objective: To explore the debulking strategy of lower extremity artery lesions. Methods: Retrospectively analyzed the clinical data of 101 patients underwent debulking therapy at Department of Vascular Surgery,Zhongshan Hospital,Fudan University from June 2019 to June 2020.There were 74 males and 27 females,aged (73.2±11.7)years (range:35 to 93 years).There were 31 cases in Rutherford class 3,39 cases in class 4 and 31 cases in class 5. Hypertension occurred in 72 patients. One hundred and forty lesions were treated in 101 patients. Among them, there were 13 lesions(9.3%) in iliac artery,72 lesions(51.4%) in superficial femoral artery,41 (29.3%) lesions in popliteal artery,10 lesions(7.1%) in tibiofibular trunk,and 4 lesions(2.9%) in below the knee artery.Percutaneous mechanical thrombectomy (PMT) was mainly used in acute thrombosis,excimer laser ablation (ELA) was mainly used for chronic in-stent restenosis and chronic stenosis or totally occlusive lesions,while directional atherectomy (DA) was mainly used for short calcified lesions. Results: All of the patients underwent debulking therapy. Eighty-two lesions(58.6%,82/140) were treated by PMT, 56 (40.0%,56/140) were treated by ELA,and 2 (1.4%,2/140) were treated by DA.The ankle-brachial index of the patient was 0.44±0.19 before surgery, 0.87±0.17 immediately after surgery (t=-16.26, P<0.01), and 0.81±0.20 at 6 months after surgery(t=-14.67,P<0.01),and 0.79±0.15 (t=-14.12,P<0.01) at 12 months after surgery. At 12 months,the primary patency was 86.1% (87/101),mortality was 5.0% (5/101), freedom from major-amputation survival rate was 93.1% (94/101),and target lesion reintervention rate was 9.9% (10/101). Conclusions: Debulking is feasible and effective to eliminate the arterial contents and maximize the acquisition of lumen.Selection of suitable debulking methods for different segments and lesions would be helpful to improve the technical success and obtain satisfactory results.

Linking Stage-Specific Plasma Biomarkers to Gray Matter Atrophy in Parkinson Disease.

BACKGROUND AND PURPOSE: The shortcomings of synucleinopathy-based Parkinson disease staging highlight the need for systematic clinicopathologic elucidation and biomarkers. In this study, we investigated associations of proteinopathy and inflammation markers with changes in gray matter volume that accompany Parkinson disease progression. MATERIALS AND METHODS: We prospectively enrolled 42 patients with idiopathic Parkinson disease, subdivided into early-/late-stage groups and 27 healthy controls. Parkinson disease severity and participants' functional and cognitive performance were evaluated. Peripheral plasma α-synuclein, ß-amyloid42, and tau were quantified with immunomagnetic reduction assays, and nuclear DNA by polymerase chain reaction, and regional gray matter volumes were determined by MR imaging. Statistical tests identified stage-specific biomarkers and gray matter volume patterns in the early-stage Parkinson disease, late-stage Parkinson disease, and control groups. Correlations between gray matter volume atrophy, plasma biomarkers, Parkinson disease severity, and cognitive performance were analyzed. RESULTS: Patients with Parkinson disease had significantly elevated α-synuclein, tau, and ß-amyloid42 levels compared with controls; nuclear DNA levels were similar in early-stage Parkinson disease and controls, but higher in late-stage Parkinson disease (all P < .01). We identified 3 stage-specific gray matter volume atrophy patterns: 1) control > early-stage Parkinson disease = late-stage Parkinson disease: right midfrontal, left lingual, and fusiform gyri, left hippocampus, and cerebellum; 2) control > early-stage Parkinson disease > late-stage Parkinson disease: precentral, postcentral, parahippocampal, left superior-temporal, right temporal, right superior-frontal, and left cingulate gyri, occipital lobe, and bilateral parts of the cerebellum; 3) control = early-stage Parkinson disease > late-stage Parkinson disease: left midfrontal, superior-frontal and temporal, amygdala, and posterior cingulate gyri, caudate nucleus, and putamen. We discovered stage-specific correlations among proteinopathy, inflammation makers, topographic gray matter volume patterns, and cognitive performance that accompanied Parkinson disease progression. CONCLUSIONS: Identifying associations linking peripheral plasma biomarkers, gray matter volume, and clinical status in Parkinson disease may facilitate earlier diagnosis and improve prognostic accuracy.

[Application and value of excimer laser ablation in the treatment of lower limb atherosclerotic obliterans].

Objective: To evaluate the results of excimer laser ablation (ELA) in the treatment of lower limb atherosclerotic obliterans (ASO). Methods: From June 2019 to March 2020, patients who underwent ELA combined with drug-coated balloon (DCB) for lower limb atherosclerotic obliterans (ASO) were enrolled. Demographics, lesion characteristics, procedure-related outcomes and complications were collected and analyzed. Results: Thirty patients were enrolled, including 21 males and 9 females. The mean age was (76.5±10.5) years. The mean lesion length was (11.7±6.4) cm. A total of 41 lesions, including in-stent restenosis (ISR) in 12 (29.3%), chronic totally occlusion (CTO) at initial treatment in 24 (58.5%), and severe stenosis in 5 (12.2%) patients. Sixteen (51.6%) patients were classified as Peripheral Arterial Calcium Scoring System (PACSS) category 4. The technical success rate was 93.5%. Incidence of distal embolization and bailout stenting was 12.9% and 6.5%, respectively. The mean follow-up time was (6.6±3.0) months. Ankle-brachial index (ABI) was significantly increased from 0.43(0.32,0.55) preoperatively to 0.91(0.87,1.01) postoperatively (Z=-5.43, P<0.01) and 0.82(0.73,1.02) (Z=-3.99, P<0.01) three months after surgery. The 3-month major-amputation free survival rate was 96.7%, primary patency rate was 100%, the target lesion reintervention (TLR) rate was 0 and ulcer healing rate was 76.9%. Conclusion: Debulking of ELA is feasible and effective for both ISR and CTO at initial treatment, providing a new option for DCB preparation and reducing stent implantation.

[Influence of thread shapes of custommade root-analogue implants on stress distribution of peri-implant bone: A three-dimensional finite element analysis].

OBJECTIVE: To explore the effects from the thread shapes of custom-made root-analogue implant (RAI) on distributions of von Mises stress around the peri-implant bone. METHODS: Five one-stage RAI three-dimensional finite element (FE) models with different thread shapes (V-shaped design, square design, buttress design, reverse buttress design and none thread design) and congruent bone were created through reverse engineering technology. The data of the five models were imported into the FE analysis software to calculate. A force of 100 N was applied parallelly and of 45° to the implant axis respectively. Analysis was performed to evaluate the von Mises stress distributions at the peri-implant regions with the help of the Ansys 16 software. RESULTS: The von Mises stresses distributed mostly at the implant cervical regions and the tip ends of the threads on the cortical bone under oblique loading, while on the cancellous bone, the stresses concentrated mostly on the implant lateral cervical regions, the tip ends of the threads and the apical regions. When under vertical loading, the von Mises stresses distributed mostly at the implant cervical regions on the cortical bone while at the tip ends of the threads and the lateral apical regions on the cancellous bone. The von Mises stresses were better distributed on the thread groups under both kinds of loadings compared with no thread design. But there was no obvious difference among the different thread groups. The concentrations of the von Mises stresses on the cancellous bone in the thread groups were mostly at the tip ends of the threads while less in the apical area. The von Mises stresses were better distributed on the cancellous bone on the other three thread designs than on square design. CONCLUSION: Thread designs are advocated for the reason that adding thread designs to the RAI standard design will have a positive effect on stress distributions at the peri-implant regions and it will reduce the concentrations of von Mises stresses on the cortical bone. From the standpoint of the stress distribution, V-shaped design, buttress design and reverse buttress design are more suitable for RAI than square design. There is no difference of the distributions of the von Mises stresses in the RAI between different thread designs.

[Optimal timing of endovascular treatment for uncomplicated Stanford type B aortic dissection].

Stanford type B aortic dissection (TBAD) is an acute and life-threatening disease. The treatment of TBAD used to be depended on whether it is complicated. The therapeutic guidelines recommend thoracic endovascular aortic repair (TEVAR) as first-line treatment for patients with acute complicated TBAD, while recommend best medical therapy for patients with acute uncomplicated TBAD (UTBAD). However, the latest studies suggest that patients with UTBAD also should be treated with pre-emptive TEVAR, which can significantly improve aortic remodeling and clinical outcome. Considering improvement of aortic remodeling and prevention of severe complications, the best timing of pre-emptive TEVAR may be 14-90 days after the onset of TBAD (subacute phase). The other main issue is identifying which patients with UTBAD should undergo pre-emptive TEVAR. Several risk factors including imaging, clinical and laboratory parameters have been shown to be associated with aortic-related events in patients with UTBAD. Among imaging finding, the diameters of aortic or false lumen, the status of true or false lumen, the size or number of entry tears have identified to be as predictors of adverse aortic events in patients with UTBAD.

Synchronous behaviour in network model based on human cortico-cortical connections.

OBJECTIVE: We consider a network topology according to the cortico-cortical connection network of the human brain, where each cortical area is composed of a random network of adaptive exponential integrate-and-fire neurons. APPROACH: Depending on the parameters, this neuron model can exhibit spike or burst patterns. As a diagnostic tool to identify spike and burst patterns we utilise the coefficient of variation of the neuronal inter-spike interval. MAIN RESULTS: In our neuronal network, we verify the existence of spike and burst synchronisation in different cortical areas. SIGNIFICANCE: Our simulations show that the network arrangement, i.e. its rich-club organisation, plays an important role in the transition of the areas from desynchronous to synchronous behaviours.

Real-Time Motor Cortex Mapping for the Safe Resection of Glioma: An Intraoperative Resting-State fMRI Study.

BACKGROUND AND PURPOSE: Resting-state functional MR imaging has been used for motor mapping in presurgical planning but never used intraoperatively. This study aimed to investigate the feasibility of applying intraoperative resting-state functional MR imaging for the safe resection of gliomas using real-time motor cortex mapping during an operation. MATERIALS AND METHODS: Using interventional MR imaging, we conducted preoperative and intraoperative resting-state intrinsic functional connectivity analyses of the motor cortex in 30 patients with brain tumors. Factors that may influence intraoperative imaging quality, including anesthesia type (general or awake anesthesia) and tumor cavity (filled with normal saline or not), were studied to investigate image quality. Additionally, direct cortical stimulation was used to validate the accuracy of intraoperative resting-state fMRI in mapping the motor cortex. RESULTS: Preoperative and intraoperative resting-state fMRI scans were acquired for all patients. Fourteen patients who successfully completed both sufficient intraoperative resting-state fMRI and direct cortical stimulation were used for further analysis of sensitivity and specificity. Compared with those subjected to direct cortical stimulation, the sensitivity and specificity of intraoperative resting-state fMRI in localizing the motor area were 61.7% and 93.7%, respectively. The image quality of intraoperative resting-state fMRI was better when the tumor cavity was filled with normal saline (P = .049). However, no significant difference between the anesthesia types was observed (P = .102). CONCLUSIONS: This study demonstrates the feasibility of using intraoperative resting-state fMRI for real-time localization of functional areas during a neurologic operation. The findings suggest that using intraoperative resting-state fMRI can avoid the risk of intraoperative seizures due to direct cortical stimulation and may provide neurosurgeons with valuable information to facilitate the safe resection of gliomas.

Anterior debridement may not be necessary in the treatment of tuberculous spondylitis of the thoracic and lumbar spine in adults: a retrospective study.

AIM: Many aspects of the surgical treatment of patients with tuberculosis (TB) of the spine, including the use of instrumentation and the types of graft, remain controversial. Our aim was to report the outcome of a single-stage posterior procedure, with or without posterior decompression, in this group of patients. PATIENTS AND METHODS: Between 2001 and 2010, 51 patients with a mean age of 62.5 years (39 to 86) underwent long posterior instrumentation and short posterior or posterolateral fusion for TB of the thoracic and lumbar spines, followed by anti-TB chemotherapy for 12 months. No anterior debridement of the necrotic tissue was undertaken. Posterior decompression with laminectomy was carried out for the 30 patients with a neurological deficit. RESULTS: The mean kyphotic angle improved from 26.1° (- 1.8° to 62°) to 15.2° (-25° to 51°) immediately after the operation. At a mean follow-up of 68.8 months (30 to 144) the mean kyphotic angle was 16.9° (-22° to 54°), with a mean loss of correction of 1.6° (0° to 10°). There was a mean improvement in neurological status of 1.2 Frankel grades in those with a neurological deficit. Bony union was achieved in all patients, without recurrent infection. CONCLUSIONS: Long posterior instrumentation with short posterior or posterolateral fusion is effective in the treatment of TB spine. It controls infection, corrects the kyphosis, and maintains correction and neurological improvement over time. TAKE HOME MESSAGE: With effective anti-TB chemotherapy, a posterior only procedure without debridement of anterior lesion is effective in the treatment of TB spondylitis, and an anterior procedure can be reserved for those patients who have not improved after posterior surgery. Cite this article: Bone Joint J 2016;98-B:834-9.

Intervention versus Aggressive Medical Therapy for Cognition in Severe Asymptomatic Carotid Stenosis.

BACKGROUND AND PURPOSE: Asymptomatic carotid stenosis of ≥70% increases the incidence of microembolism and/or chronic hypoperfusion, which may consequently impair neurocognition and brain connections. We sought controlled evidence for any cognitive benefit of aggressive medical therapy and combined carotid revascularization. MATERIALS AND METHODS: Patients with asymptomatic, unilateral, ≧70% stenosis of the extracranial ICA chose either aggressive medical therapy alone or in combination with carotid artery stent placement in this nonrandomized controlled study. They were examined with a battery of neuropsychological tests, structural MR imaging, DTI, and resting-state fMRI before and 3 months after treatment. RESULTS: Forty patients were included with 15 in the medical group and 25 in the stent-placement group. Among them, 13 and 21 in the respective groups completed neuroimaging follow-up. The baseline characteristics and the changes in cognitive performance during 3 months showed no differences between treatment groups. Nevertheless, compared with the medical group, the stent-placement group showed subjective dizziness alleviation (P = .045) and a small increase in fractional anisotropy at the splenium of the corpus callosum and the posterior periventricular white matter ipsilateral to carotid artery stent placement. Moreover, only the stent-placement group showed interval improvement in immediate memory and visuospatial performance, which was accompanied by an increase of functional connectivity at the insular cortex of the dorsal attention network and the medial prefrontal cortex of the default mode network. CONCLUSIONS: Both aggressive medical therapy alone and combined carotid revascularization in ≧70% asymptomatic carotid stenosis similarly preserved cognition during 3-month follow-up, though the latter had the potential for dizziness alleviation and cognitive and connectivity enhancement.

Brain MR Imaging Findings of Cardiac-Type Fabry Disease with an IVS4+919G>A Mutation.

BACKGROUND AND PURPOSE: A high incidence of cardiac-type Fabry disease with an α-galactosidase A mutation, IVS4 + 919 G>A, has been identified in the Taiwanese population. The neurologic manifestation has not been understood in this specific cardiac variant. This study aimed to investigate the typical imaging features of classic Fabry disease in patients with IVS4 Fabry disease. MATERIALS AND METHODS: Twenty-six patients with IVS4-type Fabry disease (20 men and 6 women; age range, 43-71 years; median age, 61 years) and 26 age- and sex-matched healthy controls (age range, 44-68 years; median age, 60 years) were analyzed for white matter hyperintensities, the pulvinar sign, and basilar artery diameter. The volumes of white matter hyperintensities were calculated by comparison with an in-house data base of 276 controls. RESULTS: Infarctions were found in 9 patients with IVS4 Fabry disease (35%) and in none of the healthy controls (P = .001). A pulvinar sign was found in 8 patients with IVS4 Fabry disease (30%) and in none of the healthy controls (P = .002). No significant difference was found in Fazekas scale scores for white matter hyperintensities; however, white matter hyperintensity volume in the deep white matter was higher in patients with IVS4 Fabry disease than in those from the healthy control data base (P = .004). CONCLUSIONS: Along with its involvement of the cardiac system, IVS4-type Fabry disease has features similar to those of classic Fabry disease and a higher frequency of deep white matter hyperintensities and a higher incidence of infarctions and pulvinar signs than in healthy controls.

Leukemia inhibitory factor (LIF) potentiates antinociception activity and inhibits tolerance induction of opioids.

BACKGROUND: The efficacy of opioids typically decreases after long-term use owing to the development of tolerance. Glial activation and the upregulation of proinflammatory cytokines are related to the induction of tolerance. We investigated the effect of leukemia inhibitory factor (LIF) on morphine analgesia and tolerance. METHODS: LIF concentrations in rat spinal cords were measured by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) after morphine administration. LIF distribution was examined using confocal microscopy. To evaluate the effects of LIF on morphine analgesia and tolerance, LIF was intrathecally administered 30 min before morphine injection. The analgesic effect of morphine was evaluated by measuring tail-flick latency. Human LIF concentrations from the cerebrospinal fluid (CSF) of opioid tolerant patients were also determined by specific ELISA. RESULTS: Chronic morphine administration upregulated LIF concentrations in rat spinal cords. Intrathecal injection of LIF potentiated the analgesic action of morphine. Patch clamp recording of spinal cord slices showed that LIF enhanced DAMGO ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin)-induced outward potassium current. The development of tolerance was markedly suppressed by exogenous LIF, whereas neutralizing the endogenously released LIF with anti-LIF antibodies accelerated the tolerance induction. Moreover, LIF concentrations in the CSF of opioid-tolerant patients were higher than those in the opioid-naive controls. CONCLUSIONS: Intrathecal administration of LIF potentiated morphine antinociceptive activity and attenuated the development of morphine tolerance. Upregulation of endogenously released LIF by long-term use of opioids might counterbalance the tolerance induction effects of other proinflammatory cytokines. LIF might be a novel drug candidate for inhibiting opioid tolerance induction.

Characteristics of sepsis-induced cardiac dysfunction using speckle-tracking echocardiography: a feasibility study.

Septic cardiomyopathy is commonly encountered in patients with severe sepsis and septic shock. This study explores whether novel global and segmental echocardiographic markers of myocardial deformation, using two-dimensional speckle tracking, are associated with adverse sepsis outcomes. We conducted a retrospective observational feasibility study, at a tertiary care centre, of patients admitted to the ICU with a diagnosis of sepsis who underwent an echocardiogram within the first week of sepsis diagnosis. Data were collected on chamber dimensions, systolic and diastolic function, demographics, haemodynamics, and laboratory parameters. Global and segmental left ventricular longitudinal strain (LVLS) and tissue mitral annular displacement (TMAD) were assessed on 12 left ventricular segments and six mitral annulus segments in apical views, respectively. We explored associations of abnormal LVLS and TMAD with duration of mechanical ventilation, hospital length of stay, and mortality. Fifty-four patients were included. Global LVLS was not associated with any of the primary study endpoints. However, reduced systolic LVLS of the basal anterior segment was associated with in-hospital mortality. There was a suggestion that patients with a reduced global TMAD were associated with an increased risk of mortality and a short length of hospital stay but these associations were not statistically significant. Reduced global LVLS was associated with lower ejection fraction. Reduced global TMAD was associated with reduced global and segmental LVLS, reduced left ventricular ejection fraction, and increased left ventricular end-systolic and end-diastolic volumes. Speckle-tracking echocardiography can be performed feasibly in patients in sepsis. Global and segmental left ventricular deformation indices are associated with ejection fraction. Further studies need to evaluate the ability of these new indices to predict sepsis outcomes.