PPA Group Research Articles

Role of pause duration in primary progressive aphasia

ABSTRACT Aims To detect differences in speech fluency in separate primary progressive aphasia syndromes (PPA) using automated analysis techniques. The resulting linguistic features are evaluated for their use in a predictive model to identify common patterns in speakers with PPA. As fluency is observable in audio recordings, its quantification may provide a low-cost instrument that augments spontaneous speech analyses in clinical practice. Methods and Procedures Speech was recorded in 14 controls, 7 nonfluent variant (nfvPPA) and 8 semantic variant (svPPA) speakers. The recordings were annotated for speech and non-speech with Kaldi, a common toolkit for speech processing software. Variables relating to fluency (pause rate, number of pauses, length of pauses) were analyzed. Outcomes and Results The best fitting distribution of pause duration was a combination of two Gaussian distributions, corresponding with pause categories short vs. long. Group level differences were found in the rate of pauses and proportion of silence: nfvPPA speakers use more short pauses relative to long pauses than control speakers, and the duration of short and long pauses is longer; svPPA speakers use more longer pauses relative to short pauses. Their short pauses are significantly shorter than those from control speakers. Participants in both PPA groups pause more frequently. SvPPA speakers are typically perceived as fluent. However, our analysis shows their fluency patterns to be distinct from control speakers, if the long-short distinction is observed. Conclusions Automatic measurements of pause duration show meaningful distinctions across the groups and might provide future aid in clinical assessment.

Executive Profile of the Logopenic Variant of Primary Progressive Aphasia: Comparison with the Semantic and Non-Fluent Variants and Alzheimer's Disease.

The logopenic variant of primary progressive aphasia (lvPPA) shows different features from the non-fluent (nfvPPA) and semantic (svPPA) variants of PPA. Although language impairments remain the core symptoms, studies have highlighted the presence of executive disorders at the onset of the disease. Nevertheless, the results are contradictory, particularly in lvPPA. The aim of this study was to explore the executive profile of lvPPA. We compared executive functioning in lvPPA with the other two variants of PPA, Alzheimer's disease (AD) and a cognitively healthy group. In total, 70 patients with PPA, 32 patients with AD, and 41 healthy controls were included. They underwent a comprehensive executive battery assessing short-term and working memory, inhibition, flexibility, planning, and initiation. The analyses showed significant differences between the lvPPA group and the control group, except on visuospatial spans and the Stroop test, and between the lvPPA group and the other PPA groups and the AD group for several tasks. Thus, this research highlighted the existence of an executive dysfunction from the onset of the disease in lvPPA but also in the other two variants of PPA.

Impact of an intrapartum care quality improvement intervention in Brazilian private hospitals on care safety measures and adverse outcomes

BackgroundIn 2015, a quality improvement (QI) intervention to reduce cesarean sections (CS)—the Adequate Childbirth Project (PPA)—was implemented in the private sector in Brazil. This analysis aims to compare safety care measures and adverse outcomes between women exposed to the PPA intervention to those receiving standard care.MethodsThe analysis included a convenience sample of 12 private hospitals that participated in the PPA (2017–2018). Data collection was performed through chart review and interviews. Differences in 15 outcomes were examined using Pearson’s chi-square test and multiple logistic regressions.ResultsThe final weighted sample was comprised of 4789 births, 2570 in the PPA group (53.5%) and 2227 in the standard care group (46.5%). CS rate was significantly lower in the PPA group (67.3% vs 88.8%). After adjusting for potential confounders, PPA model was associated with decreased overall CS rate (OR = 0.30, 95% CI 0.24 to 0.36), as well as prelabor (OR = 0.41, 0.34 to 0.48) and repeated CS (OR = 0.45, 0.29 to 0.70). In terms of other safety care measures, women in the PPA model had an increased chance of absence of antibiotic prophylaxis in Group B Streptococcus (GBS) + women (OR = 4.63, 1.33 to 16.14) and for CSs (OR = 1.75, 1.38 to 2.22), while those with severe hypertension were less likely to not receiving magnesium sulphate (OR = 0.27, 0.09 to 0.77). Regarding obstetric and neonatal outcomes, PPA model was associated with a decreased chance of having an obstetric anal sphincter injury (OASI) following an episiotomy (OR = 0.34, 0.13 to 0.89), requiring antibiotics other than routine prophylaxis (OR = 0.84, 0.70 to 0.99), having a late preterm (OR = 0.36, 0.27 to 0.48) or early term baby (OR = 0.81, 0.70 to 0.94). There were no statistically significant differences for other outcomes.ConclusionsThe PPA intervention was able to reduce CS rates, late preterm and early term deliveries without increasing the chance of adverse outcomes. The bidirectional effect on safety care measures reinforces that QI initiatives includes closer observation of routine care when implementing interventions to reduce C-section rates.

Verb production and comprehension in primary progressive aphasia

Studies of word class processing have found verb retrieval impairments in individuals with primary progressive aphasia (Bak et al., 2001; Cappa et al., 1998; Cotelli et al., 2006; Hillis, Heidler-Gary, et al., 2006; Hillis, Oh, & Ken, 2004; Marcotte et al., 2014; Rhee, Antiquena, & Grossman, 2001; Silveri & Ciccarelli, 2007; Thompson, Lukic, et al., 2012) associated primarily with the agrammatic variant. However, fewer studies have focused on verb comprehension, with inconsistent results. Because verbs are critical to both production and comprehension of clauses and sentences, we investigated verb processing across domains in agrammatic, logopenic, and semantic PPA and a group of age-matched healthy controls. Participants completed a confrontation naming task for verb production and an eye-tracking word-picture matching task for online verb comprehension. All PPA groups showed impaired verb production and comprehension relative to healthy controls. Most notably, the PPA-S group performed more poorly than the other two PPA variants in both domains. Overall, the results indicate that semantic deficits in the PPA-S extend beyond object knowledge to verbs as well, adding to our knowledge concerning the nature of the language deficits in the three variants of primary progressive aphasia.

Converging longitudinal patterns of atrophy in clinical variants of frontotemporal lobar degeneration

AbstractBackgroundThe aim of this study was to assess longitudinal patterns of atrophy shown by magnetic resonance imaging (MRI) in the whole‐brain GM of patients affected by different clinical variants of the FTLD spectrum.MethodFifty‐nine patients, including 26 with behavioral variant of frontotemporal dementia (bvFTD), 10 non‐fluent/agrammatic variant of primary progressive aphasia (nfvPPA), 12 semantic variant of PPA (svPPA), and 11 MND, in the absence of known pathogenic mutations, underwent MRI on a 3T scanner at 6‐month intervals for one year. Thirty‐three healthy controls underwent the same protocol. 3D T1‐weighted MRI sequences were analyzed using voxel‐based morphometry to assess the longitudinal evolution of GM atrophy in patients, compared with HC.ResultAt baseline, severe diffuse atrophy of frontotemporal cortical regions and basal ganglia was found in bvFTD, nfvPPA and svPPA groups, whereas MND did not show significant GM atrophy. At 6‐month follow‐up, bvFTD and PPA groups showed significant progression of atrophy in the insular (bvFTD, nfvPPA and svPPA) and anterior cingulate cortex (bvFTD and nfvPPA), bilaterally, as well as in the left caudate nucleus and middle temporal cortex (svPPA). At 12‐month follow‐up, similar patterns of atrophy progression were found, with the additional involvement of the superior frontal cortical gyri in nfvPPA, bilaterally, and the right hippocampus in svPPA. No significant progression of atrophy was found in MND patients.ConclusionOur data suggest that atrophy of insular and anterior cingulate cortical regions closely reflects the progression of neurodegeneration across the behavioral and linguistic presentations of frontotemporal dementia (FTD), in contrast with a substantial sparing of GM in MND. Supported by: European Research Council (StG‐2016_714388_NeuroTRACK).

Serum neurofilament light chain in FTLD: association with C9orf72, clinical phenotype, and prognosis.

ObjectiveThe aim of the present study was to compare the levels of serum neurofilament light chain (sNfL) in frontotemporal lobar degeneration (FTLD) patients of different clinical subtypes (bvFTD, PPA, and FTLD‐MND) and with or without the C9orf72 repeat expansion, and to correlate sNfL levels to disease progression, assessed by the brain atrophy rate and survival time.MethodsThe sNfL levels were determined from 78 FTLD patients (C9orf72 repeat expansion carriers [n = 26] and non‐carriers [n = 52]) with Single Molecule Array (SIMOA). The progression of brain atrophy was evaluated using repeated T1‐weighted MRI scans and the survival time from medical records.ResultsIn the total FTLD cohort, sNfL levels were significantly higher in C9orf72 repeat expansion carriers compared to non‐carriers. Considering clinical phenotypes, sNfL levels were higher in the C9orf72 repeat expansion carriers than in the non‐carriers in bvFTD and PPA groups. Furthermore, sNfL levels were the highest in the FTLD‐MND group (median 105 pg/mL) and the lowest in the bvFTD group (median 27 pg/mL). Higher sNfL levels significantly correlated with frontal cortical atrophy rate and subcortical grey matter atrophy rate. The higher sNfL levels also associated with shorter survival time.InterpretationOur results indicate that the C9orf72 repeat expansion carriers show elevated sNFL levels compared to non‐carriers and that the levels differ among different clinical phenotypes of FTLD. Higher sNfL levels correlated with a shorter survival time and cortical and subcortical atrophy rates. Thus, sNfL could prove as a potential prognostic biomarker in FTLD.

Exercise, headache, and factors associated with headache in chronic whiplash: Analysis of a randomized clinical trial.

Background:Almost 40% of individuals with chronic whiplash-associated disorders (WAD) report headache after 5 years, making it one of the most common persistent symptoms besides neck pain, but randomized treatment studies are lacking. This study aimed to evaluate the effect of 3 different exercise approaches on headache in chronic WAD grades 2 and 3, and to identify potential factors associated with such headache, and whether they differ depending on 3 different aspects of such headache (current headache, maximum headache, or headache bothersomeness).Methods:This was an analysis of a randomized clinical trial of people with chronic WAD and headache (n = 188), who were randomized to either 12 weeks of neck-specific exercise without (NSE) or with a behavioral approach (NSEB) or physical activity prescription (PPA). Data were collected at baseline and at 3, 6, and 12 months. Physical and psychosocial factors were tested for association with headache. Multivariate regression models and linear mixed models were used.Results:The NSE/NSEB groups reported reduced headache both over time and compared to PPA. Up to 51% (NSE) and 61% (NSEB) reported at least 50% reduction in their headache at 12 months. The PPA group was not improved over time. Neck pain and dizziness were associated with headache regardless of aspect of headache. The only associated psychosocial factor was anxiety, which was associated with headache bothersomeness. Other factors were mainly physical, and up to 51% of the variance was explained.Conclusion:Headache in chronic WAD, may be reduced with neck-specific exercise with or without a behavioral approach. Chronic headache was associated with neck pain and dizziness regardless of aspect tested. Other factors associated with headache in chronic WAD were mainly physical rather than psychosocial.Trial registration number:Clinical Trials.gov, no: NCT015285

The surgical outcome of Lisfranc injuries accompanied by multiple metatarsal fractures: A multicenter retrospective study

BackgroundThis study assessed the surgical outcomes of Lisfranc injuries accompanied by multiple metatarsal fractures. Metatarsal fractures here refers to metatarsal head, neck, and shaft (including shaft fractures accompanied by fractures of the base) fractures, as well as mixed (i.e., segmental fracture) fractures, as seen on imaging studies. MethodsBetween 2002 and 2015, one hundred and seventy-six patients were followed-up for a mean of 92 months, including eight patients who underwent secondary arthrodesis due to severe arthritis after ORIF. All the patients underwent surgical fusion (primary partial arthrodesis, PPA; n = 78) or non-fusion (percutaneous or open reduction and internal fixation, ORIF; n = 98) procedures and the outcomes were evaluated by clinical examinations, radiography, visual analogue scale (VAS) pain score, the American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score, the Foot and Ankle Outcome Score (FAOS), and the Short Form (SF)-36 physical and SF-36 mental questionnaires. The parameters between the fusion and non-fusion groups were analyzed by repeated-measures ANOVA. Statistically significant differences between the two groups were then further analyzed using a two-independent-samples t-test. ResultsAnatomical reduction was achieved in 161 patients. At the last follow-up, the mean AOFAS score was 74.67 (range: 39–91) in the non-fusion group and 82.79 (range: 67–97) in the fusion group (P = 0.003). The PPA and ORIF groups differed significantly with respect to the VAS pain score (1.93 vs. 1.21), the SF-36 physical (75.87 vs. 80.90) and mental (75.76 vs. 81.33) components, and the FAOS pain (72.74 vs. 84.06), symptoms (71.87 vs. 82.49), activities of daily life (ADLs: 73.12 vs. 81.54), sport/recreation (sport/rec: 57.99 vs. 73.23), and quality of life (QoL: 79.95 vs. 86.67) components. In the ORIF group, 23 patients had mild/moderate post-traumatic osteoarthritis. ConclusionsWith longer and more conservative postoperative management, fusion results in a better outcome than non-fusion in the treatment of Lisfranc injuries accompanied by multiple metatarsal fractures.

Effect of Hydrogen-Rich Saline on Postoperative Intra-Abdominal Adhesion Bands Formation in Mice.

BackgroundPostsurgical peritoneal adhesions (PPAs) are pathologic fibrous bands within the peritoneal cavity. The aim of this study was to investigate the protective effect of hydrogen-rich saline (HRS) on PPAs formation in mice.Material/MethodsAdhesions were induced in mice using the cecum rubbing model. The mice were allocated into 4 groups: control sham group without cecum rubbing; PPA group with saline applied intraperitoneally (i.p.) daily after cecum rubbing; PPA+HRS (5) group with 5 ml/kg of HRS applied i.p. daily after cecum rubbing; and PPA+HRS (10) group with 10 ml/kg of HRS applied i.p. daily after cecum rubbing. On the 1st, 3rd, and 7th days after the operation, mice were killed and pathological adhesion bands were quantified to detect the effect of HRS on PPAs formation.ResultsHRS did not affect PPAs formation on the 1st day, but did make a significant reduction on the 3rd and 7th days. A significant increase of t-PA and decrease of TGF-β1 and PAI-1 in the peritoneal fluids were observed in the HRS-treated groups. The levels of MDA and MPO in the HRS-treated groups were significantly lower than those in the PPA group. TNF-α and IL-6 levels in HRS-treated groups significantly decreased compared with those in the PPA group on postoperative day 3 and 7. Moreover, HRS decreased the mRNA levels of pro-inflammatory cytokines and TGF-β1 expression in the postsurgical adhesion bands.ConclusionsThese results showed that HRS had therapeutic potential for preventing PPAs formation, possibly through balancing the expression of TGF-β1, t-PA, and PAI-1, and inhibiting oxidative stress and inflammation.

Preparation of a polylactic acid knitting mesh for pelvic floor repair and in vivo evaluation

The health warning report by the Food and Drug Administration (FDA) in 2011 has drawn attention to the need for developing a suitable bio-scaffold for repairing female pelvic from disease. This work prepared a pure polylactic acid knitting mesh (PPA) and compared its structure and properties with a commercial mesh – Surgimesh® Prolapse (SP; Aspide Medical, France). Mechanical tests showed that the PPA mesh was stronger than SP with higher breaking strength and bursting strength. The in vivo property of PPA was evaluated with an animal model. Both PPA-tissue and SP-tissue were tested to have lower strength and initial elastic modulus; tissue layer played a vital role in the bio-mechanics, especially after 3 months of implantation. New tissues on the surface of PPA grew faster and thicker than that on SP at each observation period. The final shrinkage rate of PPA (2.13 ± 0.41%) was much lower than that of SP (30.35 ± 1.7%). Obvious adhesion phenomenon was observed on both PPA and SP meshes at each test point. Two meshes showed different adhesion level, that PPA was assessed of severe adhesion, even causing host tissue rupture. By histological evaluation, both PPA and SP groups showed obvious tissue inflammation reaction evidenced by rich lymphocytes. However the surrounding tissues on the PPA recovered better, with higher inflammation response scores and presence of significant vascularization and adipogenesis after six months of implantation.

A retrospective study of branch atheromatous disease: Analyses of risk factors and prognosis

The theory of branch atheromatous disease (BAD) has been commonly underused in clinical practice and research since it was proposed in 1989. In this study, we sought to explore clinical characteristics of its substypes and biomarkers for prognosis of BAD. A total of 176 consecutive patients with BAD were classified into two groups: paramedianpontine artery group (PPA group, n=70) and lenticulostriate artery group (LSA group, n=106). Bivariate analyses were used to explore the relationship between white matter hyperintensities (WMHs), National Institutes of Health Stroke Scale (NIHSS) scores and prognosis evaluated by the modified Rank Scale (mRS) at 6th month after stroke. The differences in prevalence of diabetes mellitus and a history of ischemic heart disease were statistically significant between PPA group and LSA group (χ 2=8.255, P=0.004; χ 2=13.402, P<0.001). The bivariate analyses demonstrated a positive correlation between NIHSS and poor prognosis in patients with BAD and in the two subtype groups, and a positive correlation between WMHs and poor prognosis in the PPA group. It is concluded that a significantly higher prevalence of diabetes mellitus and a history of ischemic heart disease exist in the PPA group than in the LSA group. In addition, high grades of NIHSS scores imply poor prognosis in patients with BAD and in the two subtype groups. Moreover, WMHs are a positive predictor for poor prognosis in patients in the PPA group.

In Vitro Evaluation of Photodynamic Therapy using Different Photosensitizers on Leishmania Tropica Promastigotes

Photodynamic therapy (PDT) is an alternative treatment method which uses a photosensitizer activated in the presence of light and molecular oxygen to produce reactive oxygen species that eventually target cell death by apoptosis or necrosis. The purpose of this study was to determine the efficiency of chloroaluminum phthalocyanine (AlClPc), toludine blue (TB) and phenorforbide a (PPa) mediated PDT in exerting morphological and apoptotic changes in Leishmania tropica. Parasites were incubated with increasing concentrations of TB, AlClPc and PPa for one hour and then were illuminated with a white light source for 30 min. After incubation at 26°C for 18 hours, cell viability (analyzed using a hemocytometer and XTT colorimetric assay), morphological changes (determined by giemsa staining) and apoptotic markers (analyzed by DAPI staining and DNA fragmentation assay) of Leishmania tropica parasites were evaluated as a function of TB, AlClPc and PPa concentration. Parasite viability was significantly different in between the groups treated with TB and PPa, with or without irradiation. There were no statistically significant differences in cell viability of AlClPc treated Leishmania tropica promastigotes with and without irradiation. Also, DAPI staning results indicated that apoptotic bodies and nucleus fragmentation started to be visible in AlClPc and PPa mediated PDT groups. Furthermore, DNA ladder pattern which is used to define apoptosis, was observed in irradiated AlClPc and PPa groups, but not observed in irradiated TB, non-irradiated AlClPc, TB and PPa. Although TB and AlClPc mediated PDT has been used for other Leishmania species but not on Leishmania tropica, this study is first to demonstrate the efficiency of PPa mediated PDT in a Leishmania spp. However, it is crucial to verify the photoactivity of these compounds in axenic or intracellular amastigotes and further in animal models.

IDH1 R132H Mutation Is Accompanied with Malignant Progression of Paired Primary-Recurrent Astrocytic Tumours.

IDH1 R132H mutation is an important marker of survival in patients with gliomas. Although there are many changes of genes in tumour malignant progression, IDH1 R132H mutation status in glioma progression remained unclear. Here, an in-depth characterization of IDH1 R132H mutations were assessed by immunohistochemistry in 55 paired primary-recurrent astrocytomas tissues, including 5 paired primary pilocytic astrocytoma (pPA, WHO grade I), 35 paired primary low grade astrocytoma (pLGA, WHO grade II and III) and 15 paired primary high grade astrocytoma (pHGA/ Glioblastoma, WHO grade IV). Meanwhile, the DNA was isolated from paired samples, and PCR amplification was used for IDH1 exon4 sequencing. Nonparametric test, KM and Cox models were used to examine the statistical difference and survival function. We found that the percent of IDH1 R132H mutation was 68.6% (24/35) in pLGA group, but no IDH1 mutation was found in pPA and pHGA groups. Meanwhile, the results from immunohistochemistry and DNA sequencing showed that, compared with primary astrocytoma, there was no change of IDH1 status in recurrent astrocytoma whatever tumour pathological grade raise or indolent. The pPA group has the longest recurrence-free period (RFP) and overall survival (OS) in three groups (p<0.01), while the pHGA group has the shortest ones (p<0.01). In pLGA group, the IDH1 R132H mutation subgroup has longer RFP than IDH1 wild type subgroup (p<0.01), but the OS has no statistical difference between two subgroups (p>0.6). Additionally, IDH1 R132H mutation independently predicted a long RFP in patients with pLGA (HR 1.073, 95% CI 0.151-0.775, p<0.01).

Emotion detection deficits and changes in personality traits linked to loss of white matter integrity in primary progressive aphasia.

Non-cognitive features including personality changes are increasingly recognized in the three PPA variants (semantic-svPPA, non fluent-nfvPPA, and logopenic-lvPPA). However, differences in emotion processing among the PPA variants and its association with white matter tracts are unknown. We compared emotion detection across the three PPA variants and healthy controls (HC), and related them to white matter tract integrity and cortical degeneration. Personality traits in the PPA group were also examined in relation to white matter tracts. Thirty-three patients with svPPA, nfvPPA, lvPPA, and 32 HC underwent neuropsychological assessment, emotion evaluation task (EET), and MRI scan. Patients' study partners were interviewed on the Clinical Dementia Rating Scale (CDR) and completed an interpersonal traits assessment, the Interpersonal Adjective Scale (IAS). Diffusion tensor imaging of uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), and voxel-based morphometry to derive gray matter volumes for orbitofrontal cortex (OFC), anterior temporal lobe (ATL) regions were performed. In addition, gray matter volumes of white matter tract-associated regions were also calculated: inferior frontal gyrus (IFG), posterior temporal lobe (PTL), inferior parietal lobe (IPL) and occipital lobe (OL). ANCOVA was used to compare EET performance. Partial correlation and multivariate linear regression were conducted to examine association between EET and neuroanatomical regions affected in PPA. All three variants of PPA performed significantly worse than HC on EET, and the svPPA group was least accurate at recognizing emotions. Performance on EET was related to the right UF, SLF, and ILF integrity. Regression analysis revealed EET performance primarily relates to the right UF integrity. The IAS subdomain, cold-hearted, was also associated with right UF integrity. Disease-specific emotion recognition and personality changes occur in the three PPA variants and are likely associated with disease-specific neuroanatomical changes. Loss of white matter integrity contributes as significantly as focal atrophy in behavioral changes in PPA.

Longitudinal white matter change in frontotemporal dementia subtypes and sporadic late onset Alzheimer's disease.

BackgroundDegradation of white matter microstructure has been demonstrated in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). In preparation for clinical trials, ongoing studies are investigating the utility of longitudinal brain imaging for quantification of disease progression. To date only one study has examined sample size calculations based on longitudinal changes in white matter integrity in FTLD.ObjectiveTo quantify longitudinal changes in white matter microstructural integrity in the three canonical subtypes of frontotemporal dementia (FTD) and AD using diffusion tensor imaging (DTI).Methods60 patients with clinical diagnoses of FTD, including 27 with behavioral variant frontotemporal dementia (bvFTD), 14 with non-fluent variant primary progressive aphasia (nfvPPA), and 19 with semantic variant PPA (svPPA), as well as 19 patients with AD and 69 healthy controls were studied. We used a voxel-wise approach to calculate annual rate of change in fractional anisotropy (FA) and mean diffusivity (MD) in each group using two time points approximately one year apart. Mean rates of change in FA and MD in 48 atlas-based regions-of-interest, as well as global measures of cognitive function were used to calculate sample sizes for clinical trials (80% power, alpha of 5%).ResultsAll FTD groups showed statistically significant baseline and longitudinal white matter degeneration, with predominant involvement of frontal tracts in the bvFTD group, frontal and temporal tracts in the PPA groups and posterior tracts in the AD group. Longitudinal change in MD yielded a larger number of regions with sample sizes below 100 participants per therapeutic arm in comparison with FA. SvPPA had the smallest sample size based on change in MD in the fornix (n = 41 participants per study arm to detect a 40% effect of drug), and nfvPPA and AD had their smallest sample sizes based on rate of change in MD within the left superior longitudinal fasciculus (n = 49 for nfvPPA, and n = 23 for AD). BvFTD generally showed the largest sample size estimates (minimum n = 140 based on MD in the corpus callosum). The corpus callosum appeared to be the best region for a potential study that would include all FTD subtypes. Change in global measure of functional status (CDR box score) yielded the smallest sample size for bvFTD (n = 71), but clinical measures were inferior to white matter change for the other groups.ConclusionsAll three of the canonical subtypes of FTD are associated with significant change in white matter integrity over one year. These changes are consistent enough that drug effects in future clinical trials could be detected with relatively small numbers of participants. While there are some differences in regions of change across groups, the genu of the corpus callosum is a region that could be used to track progression in studies that include all subtypes.

Effects of Constant Flow vs. Constant Pressure Perfusion on Fluid Filtration in Severe Hypothermic Isolated Blood-Perfused Rat Lungs.

Victims of severe accidental hypothermia are prone to fluid extravasation but rarely develop lung edema. We hypothesize that combined hypothermia-induced increase in pulmonary vascular resistance (PVR) and a concomitant fall in cardiac output protect the lungs against edema development. Our aim was to explore in hypothermic-isolated blood-perfused rat lungs whether perfusion at constant pressure influences fluid filtration differently from perfusion at constant flow. Isolated blood-perfused rat lungs were hanging freely in a weight transducer for measuring weight changes (ΔW). Fluid filtration coefficient (Kfc), was determined by transiently elevating left atrial pressure (Pla) by 5.8 mmHg two times each during normothermia (37°C) and during hypothermia (15°C). The lung preparations were randomized to two groups. One group was perfused with constant flow (Constant flow group) and the other group with constant pulmonary artery pressure (Constant PPA group). Microvascular pressure (Pmv) was determined before and during elevation of Pla (ΔPmv) by means of the double occlusion technique. Kfc was calculated with the formula Kfc = ΔW/ΔPmv/min. All Kfc values were normalized to predicted lung weight (PLW), which was based on body weight (BW) according to the formula: PLW = 0.0053 BW - 0.48 and presented as KfcPLW in mg/min/mmHg/g. At cessation, bronchoalveolar lavage (BAL) fluid/perfusate protein concentration (B/P) ratio was determined photometrically. Data were analyzed with parametric or non-parametric tests as appropriate. p < 0.05 considered as significant. Perfusate flow remained constant in the Constant flow group, but was more than halved during hypothermia in the Constant PPA group concomitant with a more fold increase in PVR. In the Constant flow group, KfcPLW and B/P ratio increased significantly by more than 10-fold during hypothermia concerted by visible signs of edema in the trachea. Hemoglobin and hematocrit increased within the Constant flow group and between the groups at cessation of the experiments. In hypothermic rat lungs perfused at constant flow, fluid filtration coefficient per gram PLW and B/P ratio increased more than 10-fold concerted by increased hemoconcentration, but the changes were less in hypothermic lungs perfused at constant PPA.

The complement system is activated in synovial fluid from subjects with knee injury and from patients with osteoarthritis.

BackgroundThe complement system is suggested to be involved in the pathogenesis of osteoarthritis (OA), and proinflammatory cytokines may play a role in OA development by inducing proteases. The association between complement factors, cytokines and OA has not been investigated. The aim of the present study was to explore the involvement of the complement system after knee trauma and in OA.MethodsC4d, C3bBbP and soluble terminal complement complex (sTCC) resulting from complement activation were immunoassayed in synovial fluid from subjects with healthy knees (reference), OA, rheumatoid arthritis (RA; positive control), pyrophosphate arthritis (PPA; positive control) and knee injury; other biomarkers were previously assessed. Magnetic resonance imaging was used to assess joint injuries.ResultsCompared with levels in the reference group, the median concentrations of C4d, C3bBbP and sTCC in the OA, RA, PPA and knee injury groups were 2- to 34-fold increased (p < 0.001 to p = 0.044). For the knee injury group, the median concentrations of C4d, C3bBbP and sTCC were 5- to 12-fold increased (p < 0.001) at the day of injury; after 3–12 weeks, C3bBbP and sTCC concentrations were similar to reference levels; and C4d was still increased several years after injury. In the 0–12 weeks period after injury, the concentrations of C4d, C3bBbP and sTCC correlated positively with levels of interleukin (IL)-1β, IL-6 and tumour necrosis factor α (r s range 0.232–0.547); none of the measured complement factors correlated with proteolytic fragments of aggrecan or cartilage oligomeric matrix protein. Knees with osteochondral fracture, with or without disrupted cortical bone, had higher concentrations of C4d (p = 0.014, p = 0.004) and sTCC (p = 0.004, p < 0.001) compared with knees without fractures.ConclusionsThe complement system is activated in OA and after knee injury. Following knee injury, this activation is instant and associated with inflammation as well as with the presence of osteochondral fractures.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1123-x) contains supplementary material, which is available to authorized users.

Ultrasound-Assisted Thoracic Paravertebral Block Reduces Intraoperative Opioid Requirement and Improves Analgesia after Breast Cancer Surgery: A Randomized, Controlled, Single-Center Trial.

ObjectivesThe contribution of ultrasound-assisted thoracic paravertebral block to postoperative analgesia remains unclear. We compared the effect of a combination of ultrasound assisted-thoracic paravertebral block and propofol general anesthesia with opioid and sevoflurane general anesthesia on volatile anesthetic, propofol and opioid consumption, and postoperative pain in patients having breast cancer surgery.MethodsPatients undergoing breast cancer surgery were randomly assigned to ultrasound-assisted paravertebral block with propofol general anesthesia (PPA group, n = 121) or fentanyl with sevoflurane general anesthesia (GA group, n = 126). Volatile anesthetic, propofol and opioid consumption, and postoperative pain intensity were compared between the groups using noninferiority and superiority tests.ResultsPatients in the PPA group required less sevoflurane than those in the GA group (median [interquartile range] of 0 [0, 0] vs. 0.4 [0.3, 0.6] minimum alveolar concentration [MAC]-hours), less intraoperative fentanyl requirements (100 [50, 100] vs. 250 [200, 300]μg,), less intense postoperative pain (median visual analog scale score 2 [1, 3.5] vs. 3 [2, 4.5]), but more propofol (median 529 [424, 672] vs. 100 [100, 130] mg). Noninferiority was detected for all four outcomes; one-tailed superiority tests for each outcome were highly significant at P<0.001 in the expected directions.ConclusionsThe combination of propofol anesthesia with ultrasound-assisted paravertebral block reduces intraoperative volatile anesthetic and opioid requirements, and results in less post operative pain in patients undergoing breast cancer surgery.Trial RegistrationClinicalTrial.gov NCT00418457

Haemodynamic Optimization by Oesophageal Doppler and Pulse Power Wave Analysis in Liver Surgery: A Randomised Controlled Trial.

Liver surgery is still associated with a high rate of morbidity and mortality. We aimed to compare different haemodynamic treatments in liver surgery. In a prospective, blinded, randomised, controlled pilot trial patients undergoing liver resection were randomised to receive haemodynamic management guided by conventional haemodynamic parameters or by oesophageal Doppler monitor (ODM, CardioQ-ODM) or by pulse power wave analysis (PPA, LiDCOrapid) within a goal-directed algorithm adapted for liver surgery. The primary endpoint was stroke volume index before intra-operative start of liver resection. Secondary endpoints were the haemodynamic course during surgery and postoperative pain levels. Due to an unbalance in the extension of the surgical procedures with a high rate of only minor procedures the conventional group was dropped from the analysis. Eleven patients in the ODM group and 10 patients in the PPA group were eligible for statistical analysis. Stroke volume index before start of liver resection was 49 (37; 53) ml/m2 and 48 (41; 56) ml/m2 in the ODM and PPA group, respectively (p=0.397). The ODM guided group was haemodynamically stable as shown by ODM and PPA measurements. However, the PPA guided group showed a significant increase of pulse-pressure-variability (p=0.002) that was not accompanied by a decline of stroke volume index displayed by the PPA (p=0.556) but indicated by a decline of stroke volume index by the ODM (p<0.001). The PPA group had significantly higher postoperative pain levels than the ODM group (p=0.036). In conclusion, goal-directed optimization by ODM and PPA showed differences in intraoperative cardiovascular parameters indicating that haemodynamic optimization is not consistent between the two monitors.Trial RegistrationISRCTN.com ISRCTN64578872

Thoracic paravertebral regional anesthesia improves analgesia after breast cancer surgery: a randomized controlled multicentre clinical trial.

The contribution of regional anesthesia with thoracic paravertebral blockade to postoperative analgesia remains unclear. We compared the effect of a combination of paravertebral blockade and propofol general anesthesia (GA) with sevoflurane GA and opioid analgesia on postoperative pain and opioid use for patients undergoing breast cancer surgery. Patients having breast cancer surgery were randomly assigned to paravertebral analgesia with propofol GA (PPA, n=187) or sevoflurane GA with perioperative opioid analgesia (SOA, n=199). The PPA and SOA groups were compared for opioid consumption and pain outcomes (on a 0-10 visual analogue scale [VAS]) at two hours postoperatively using superiority and inferiority statistics. We compared our results with previous publications in a meta-analysis. Compared with the SOA group, the PPA group experienced reduced median [interquartile range] pain VAS scores (1 [1,3] vs 2.5 [1,4], respectively; median difference -1.0; 99% confidence intervals [CI]: -1.5 to -0.5) and required less intraoperative fentanyl (50 [0, 125] µg vs 200 [100, 300] µg, respectively; median difference -100; 99% CI: -150 to -100) and less long-acting opioid (0 [0, 0] mg vs 3.0 [0, 12] mg, respectively, morphine equivalents; median difference -3; 99% CI: -4 to -2). Thus, non-inferiority was detected for all the above outcomes, and superiority tests for each outcome were highly significant in the expected directions (P<0.001). Meta-analysis, including the current study, estimated a reduction in worst pain of 2.3 points (95% CI: 1.8 to 2.8) on a 0-10 scale and a 72% reduction (95% CI: 42 to 87) in mean opioid consumption in the immediate two postoperative hours for PPA vs SOA. Our results were largely consistent with previous much smaller studies. Compared with sevoflurane GA with opioid analgesia, the combination of paravertebral analgesia with propofol GA provides an early clinical analgesic benefit in females having breast cancer surgery. This analysis is a substudy of an ongoing multicentre double-blinded randomized trial ( www.clinicaltrials.gov , NCT00418457) of cancer recurrence.