Influence of continuous subcutaneous apomorphine infusion on cognition and behavior in Parkinson's disease: A systematic review.

INTRODUCTION: The efficacy of continuous subcutaneous apomorphine infusion (CSAI) for motor complications of Parkinson's disease (PD) is established. However, its effect on cognition and behavior remains controversial. The main objective of this systematic review was to describe the existing literature on the effects of CSAI on cognition and behavior and to determine the quality for each study. METHODS: PubMed/Medline, Embase, APA PsycInfo®, and Cochrane Library databases were searched, following PRISMA recommendations. Only longitudinal studies evaluating the effect of CSAI on cognition (global cognition, executive functions, visuospatial abilities, language, memory, attention, social cognition) and/or behavior (depression, anxiety, apathy, psychotic symptoms, impulse control disorders, neuropsychiatric fluctuations) in PD were included. The quality of the included studies was also assessed with a questionnaire. RESULTS: Twenty-three longitudinal studies evaluated the effect of CSAI on cognition and/or behavior. Overall, results were suggestive of positive effects, notably on executive functions and emotion recognition. However, there were some reports of cognitive slowing and long-term global cognitive deterioration. At the behavioral level, no study showed significant adverse effect of CSAI. Occasionally, a slight improvement of depression, anxiety, apathy, and neuropsychiatric fluctuations was reported. Nevertheless, only four studies met good quality criteria and controlled study regarding cognition were lacking. CONCLUSION: The results suggest that CSAI has no obvious negative effects on cognition and behavior in PD. This treatment even shows promise in reducing certain symptoms such as neuropsychiatric fluctuations. However, due to methodological limitations in many studies, no robust conclusions can be drawn. Further multicenter controlled trials are needed to confirm these results.

High-'n'-dry? A comparison of cannabis and alcohol use in drivers presenting to hospital after a vehicular collision.

DESIGN: This was a prospective observational study. BACKGROUND AND AIMS: The characteristics of cannabis-involved motor vehicle collisions are poorly understood. This study of injured drivers identifies demographic and collision characteristics associated with high tetrahydrocannabinol (THC) concentrations. SETTING: The study was conducted in 15 Canadian trauma centres between January 2018 and December 2021. CASES: The cases (n = 6956) comprised injured drivers who required blood testing as part of routine trauma care. MEASUREMENTS: We quantified whole blood THC and blood alcohol concentration (BAC) and recorded driver sex, age and postal code, time of crash, crash type and injury severity. We defined three driver groups: high THC (THC ≥ 5 ng/ml and BAC = 0), high alcohol (BAC ≥ 0.08% and THC = 0) and THC/BAC-negative (THC = 0 = BAC). We used logistic regression techniques to identify factors associated with group membership. FINDINGS: Most injured drivers (70.2%) were THC/BAC-negative; 1274 (18.3%) had THC > 0, including 186 (2.7%) in the high THC group; 1161 (16.7%) had BAC > 0, including 606 (8.7%) in the high BAC group. Males and drivers aged less than 45 years had higher adjusted odds of being in the high THC group (versus the THC/BAC-negative group). Importantly, 4.6% of drivers aged less than 19 years had THC ≥ 5 ng/ml, and drivers aged less than 19 years had higher unadjusted odds of being in the high THC group than drivers aged 45-54 years. Males, drivers aged 19-44 years, rural drivers, seriously injured drivers and drivers injured in single-vehicle, night-time or weekend collisions had higher adjusted odds ratios (aORs) for being in the high alcohol group (versus THC/BAC-negative). Drivers aged less than 35 or more than 65 years and drivers involved in multi-vehicle, daytime or weekday collisions had higher adjusted odds for being in the high THC group (versus the high BAC group). CONCLUSIONS: In Canada, risk factors for cannabis-related motor vehicle collisions appear to differ from those for alcohol-related motor vehicle collisions. The collision factors associated with alcohol (single-vehicle, night-time, weekend, rural, serious injury) are not associated with cannabis-related collisions. Demographic factors (young drivers, male drivers) are associated with both alcohol and cannabis-related collisions, but are more strongly associated with cannabis-related collisions.

Reliability of hemostasis biomarkers is affected by time-dependent intra-patient variability.

Essentials Nucleosomes and free DNA are two newly described biomarkers in venous thromboembolism (VTE). Reliability of nucleosomes, plasma free DNA and conventional hemostasis markers were studied. Hemostasis biological parameters vary over a short time-frame in VTE patients. Hemostasis biological parameters also vary over a short time-frame in healthy controls. SUMMARY: Background Previous studies have associated neutrophil-derived circulating nucleosomes and plasma free DNA with venous thromboembolism (VTE). However, there are few data concerning these two biomarkers and no studies have compared the reliability of nucleosomes and plasma free DNA against that of conventional hemostasis markers. Objectives We performed a 3-year prospective study of nucleosomes and plasma free DNA levels in comparison with conventional hemostatic biomarkers and blood cells. Patients/Methods Fifteen healthy controls and 22 randomly selected patients with a history of VTE were followed monthly for 6 months. The reliability of these markers was evaluated by the intraclass correlation coefficient (ICCs). Results and Conclusions In healthy controls and patients, we found a low reliability for nucleosomes and plasma free DNA, with ICCs at 0.538 (95% confidence interval [CI], 0.334-0.764) and 0.091 (95% CI, -0.026-0.328), respectively, in the healthy controls, and at 0.213 (95% CI, 0.042-0.463) and 0.161 (CI 95%, 0.008-0.398) in the patient group. For the conventional hemostasis biomarkers and for blood cells, reliability ranged from poor to good in the healthy volunteers and from poor to acceptable in the patient group. Our study shows for the first time that hemostasis biological parameters spontaneously vary over a short time-frame in VTE patients and, more surprisingly, in normal individuals. The clinical value of such intra-individual variations is currently unknown. This variability might mean reinterpreting diagnostic or prognostic models based on static evaluation of individuals. Studying the intrinsic value of individual patterns of markers' variability is warranted.

Prognostic significance of central venous-to-arterial carbon dioxide difference during the first 24 hours of septic shock in patients with and without impaired cardiac function.

OBJECTIVE: To investigate the prognostic significance of central venous-to-arterial carbon dioxide difference (cv-art CO 2 gap) during septic shock in patients with and without impaired cardiac function. METHODS: We performed a prospective cohort study in 10 French intensive care units. Patients suffering from septic shock were assigned to the impaired cardiac function group ('cardiac group', n =123) if they had atrial fibrillation (AF) and/or left ventricular ejection fraction (LVEF) <50% at study entry and to the non-cardiac group ( n =240) otherwise. RESULTS: Central venous and arterial blood gases were sampled every 6 h during the first 24 h to calculate cv-art CO 2 gap. Patients in the cardiac group had a higher cv-art CO 2 gap [at study entry and 6 and 12 h (all P <0.02)] than the non-cardiac group. Patients in the cardiac group with a cv-art CO 2 gap >0.9 kPa at 12 h had a higher risk of day 28 mortality (hazard ratio=3.18; P =0.0049). Among the 59 patients in the cardiac group with mean arterial pressure (MAP) ≥65 mm Hg, central venous pressure (CVP) ≥8 mm Hg and central venous oxygen saturation (ScvO 2 ) ≥70% at 12 h, those with a high cv-art CO 2 gap (>0.9 kPa; n =19) had a higher day 28 mortality (37% vs. 13%; P =0.042). In the non-cardiac group, a high cv-art CO 2 gap was not linked to a higher risk of day 28 death, whatever the threshold value of the cv-art CO 2 gap. CONCLUSION: Patients with septic shock and with AF and/or low LVEF were more prone to a persistent high cv-art CO 2 gap, even when initial resuscitation succeeded in normalizing MAP, CVP, and ScvO 2 . In these patients, a persistent high cv-art CO 2 gap at 12 h was significantly associated with higher day 28 mortality.

Enhanced complexity of optical chaos in a laser diode with phase-conjugate feedback.

We demonstrate numerically that a semiconductor laser subjected to phase-conjugate feedback (PCF) can exhibit an enhancement in the complexity of chaos by comparison to conventional optical feedback. Using quantifiers from spectral analysis and information theory, we demonstrate that under similar parametric conditions, PCF exhibits a larger chaotic bandwidth and higher spectral flatness and statistical complexity. These properties are of utmost importance for applications in secure communications and random number generation.

Physical random bit generation from chaotic solitary laser diode.

We demonstrate the physical generation of random bits at high bit rates (> 100 Gb/s) using optical chaos from a solitary laser diode and therefore without the complex addition of either external optical feedback or injection. This striking result is obtained despite the low dimension and relatively small bandwidth of the laser chaos, i.e. two characteristics that have been so far considered as limiting the performances of optical chaos-based applications. We unambiguously attribute the successful randomness at high speed to the physics of the laser chaotic polarization dynamics and the resulting growth rate of the dynamical entropy.

Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia.

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia.

Bistability of time-periodic polarization dynamics in a free-running VCSEL.

We report experimentally a bistability between two limit cycles (i.e. time-periodic dynamics) in a free-running vertical-cavity surface-emitting laser. The two limit cycles originate from a bifurcation on two elliptically polarized states which exhibit a small frequency difference and whose main axes are symmetrical with respect to the linear polarization eigenaxes at threshold. We demonstrate theoretically that this peculiar behavior can be explained in the framework of the spin-flip model model by taking into account a small misalignment between the phase and amplitude anisotropies.

Pulmonary toxicity associated with the use of lenalidomide: case report of late-onset acute respiratory distress syndrome and literature review.

Lenalidomide is an immunomodulating drug structurally similar to thalidomide. It is indicated for patients with relapsing or refractory multiple myeloma in combination with dexamethasone, and for patients with myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality. It is also used to treat other myelodysplastic syndromes such as myelofibrosis and lymphoma. We report a case of organizing pneumonia leading to acute respiratory distress syndrome (ARDS) after long-term administration of lenalidomide, along with a review of the literature.

Potential role of Alternaria and Cladosporium species in canine lymphoplasmacytic rhinitis.

OBJECTIVES: To evaluate the possible role of Alternaria and Cladosporium species in the pathogenesis of canine lymphoplasmacytic rhinitis by comparing the amount of specific fungal DNA in nasal mucosal biopsies between dogs without nasal neoplasia and those with lymphoplasmacytic rhinitis or nasal neoplasia. METHODS: Quantitative real-time polymerase chain reaction (qPCR) assays detecting DNA from Alternaria and Cladosporium fungi were applied to nasal mucosal biopsies collected from dogs with lymphoplasmacytic rhinitis (n = 8), dogs with nasal neoplasia (n = 10) and control animals (n = 10). A copy number for each sample was calculated using a standard curve of known copy number and differences amongst groups were assessed using Kruskal-Wallis tests. RESULTS: No significant difference was found between the groups. Low levels of Alternaria DNA (10-100 copies/PCR) were detected in one sample; very low levels of DNA (<10 copies/qPCR) were detected in 6 samples, and 21 samples were negative. Low levels of Cladosporium DNA were detected in 2 samples; very low levels of DNA in 18; and 8 were negative. CLINICAL SIGNIFICANCE: Results of this study reveal that Alternaria and Cladosporium species are part of the canine nasal flora, and that these fungi are probably not involved in the pathogenesis of lymphoplasmacytic rhinitis.

Hashimoto's encephalopathy in the intensive care unit.

BACKGROUND: Since the first description of Hashimoto's Encephalitis (HE) in 1966 by Lord Brain, the number of reported cases has continued to increase. In addition, cases of status epilepticus have been reported, suggesting a role for intensive care unit (ICU) practitioners in taking care of patients with HE. METHODS: A retrospective cohort study in ICU patients with HE was performed at the University Hospital of Tours, France. RESULTS: Eight HE cases were admitted to the ICU between 1/1/2000 and 1/1/2012. Herein, we describe the characteristics of the patients, with an emphasis on ICU disease management and its outcome. CONCLUSION: ICU practitioners should be aware of this disease, since it can include life-threatening presentations.

Brachial cuff measurements of blood pressure during passive leg raising for fluid responsiveness prediction.

OBJECTIVE: The passive leg raising maneuver (PLR) for fluid responsiveness testing relies on cardiac output (CO) measurements or invasive measurements of arterial pressure (AP) whereas the initial hemodynamic management during shock is often based solely on brachial cuff measurements. We assessed PLR-induced changes in noninvasive oscillometric readings to predict fluid responsiveness. STUDY DESIGN: Multicentre interventional study. PATIENTS AND METHODS: In ICU sedated patients with circulatory failure, AP (invasive and noninvasive readings) and CO measurements were performed before, during PLR (trunk supine, not modified) and after 500-mL volume expansion. Areas under the ROC curves (AUC) were determined for fluid responsiveness (>10% volume expansion-induced increase in CO) prediction. RESULTS: In 112 patients (19% with arrhythmia), changes in noninvasive systolic AP during PLR (noninvasiveΔ(PLR)SAP) only predicted fluid responsiveness (cutoff 17%, n=21, positive likelihood ratio [LR] of 26 [18-38]), not unresponsiveness. If PLR-induced change in central venous pressure (CVP) was at least of 2 mm Hg (n=60), suggesting that PLR succeeded in altering cardiac preload, noninvasiveΔ(PLR)SAP performance was good: AUC of 0.94 [0.85-0.98], positive and negative LRs of 5.7 [4.6-6.8] and 0.07 [0.009-0.5], respectively, for a cutoff of 9%. Of note, invasive AP-derived indices did not outperform noninvasiveΔ(PLR)SAP. CONCLUSION: Regardless of CVP (i.e., during "blind PLR"), noninvasiveΔ(PLR)SAP more than 17% reliably identified fluid responders. During "CVP-guided PLR", in case of sufficient change in CVP, noninvasiveΔ(PLR)SAP performed better (cutoff of 9%). These findings, in sedated patients who had already undergone volume expansion and/or catecholamines, have to be verified during the early phase of circulatory failure (before an arterial line and/or a CO measuring device is placed).

Toll- and NOD-like receptor mRNA expression in canine sino-nasal aspergillosis and idiopathic lymphoplasmacytic rhinitis.

The pathogenesis of canine sino-nasal aspergillosis (SNA) and lymphoplasmacytic rhinitis (LPR) remains poorly understood. The innate immune system is implicated in the etiology of human chronic rhinosinusitis. Therefore, we hypothesized that dysfunction in innate immunity could be implicated in the pathogenesis of SNA and LPR. Expression of messenger RNA (mRNA) encoding Toll-like receptors (TLRs) 1-10 and NOD-like receptors (NODs) 1 and 2 in nasal mucosal biopsies from SNA or LPR dogs was compared with mucosa from healthy controls. Gene expression was quantified using quantitative real-time reverse transcriptase polymerase chain reaction normalized against multiple housekeeper genes. All TLR and NOD genes were quantified in all samples. SNA was associated with significantly increased expression of TLRs 1-4, 6-10; and NOD2, relative to controls. LPR was associated with significantly increased expression of TLRs 1, 2, 6-8, relative to controls. There was significantly more expression of TLRs 1, 4, 6-10 and NOD2 in SNA dogs than in LPR dogs. The significance of these differences in the pathogenesis of these diseases is yet to be determined.

Influence of age on bronchoscopic findings in healthy beagle dogs.

The aims of this study were to evaluate the effect of age on bronchoscopic features and bronchoalveolar lavage fluid (BALF) cellularity in dogs. Thirty healthy beagle dogs from three age groups were included: young dogs (10 months to 4.5 years of age; n=8), middle-aged dogs (5-8 years old; n=13) and older dogs (>8 years; n=9). Haematology, thoracic radiography, bronchoscopy and bronchoalveolar lavage were performed; bronchoscopic findings were scored and BALF total and differential cell counts were determined. The total bronchoscopic score was higher in older dogs; these dogs had more irregular bronchial mucosa, more prominent mucosal vessels and bronchiectasis. Younger dogs had a higher percentage of neutrophils in BALF compared with middle-aged and old dogs and a higher percentage of lymphocytes in BALF compared with middle-aged dogs. The results show that age has an effect on bronchoscopic features of airways and the composition of BALF in the dog.

Paternal endothelial protein C receptor 219Gly variant as a mild and limited risk factor for deep vein thrombosis during pregnancy.

BACKGROUND: Half of all venous thromboembolism (VTE) cases during pregnancy are associated with a maternal thrombophilia. The influence of paternal genotype on the placenta and in the genesis of VTE has not been described. OBJECTIVES: To determine if the maternal and paternal Ser219Gly dimorphism of the endothelial protein C receptor (EPCR), evaluated through detection of the PROCR 6936G allele, is a risk factor for VTE during pregnancy. METHODS: Using a case-control study nested in the NOHA first cohort of primigravidae, 66 patient couples with a first episode of gestational VTE and randomly selected non-thrombotic control couples were investigated. For each couple, factor V gene (F5) G1691A, factor II gene (F2) G20210A, factor XII gene (F12) C46T and PROCR A6936G polymorphisms were determined. RESULTS: Only maternal F5 1691A, F2 20210A and F12 46T alleles were independently associated with iliac and infra-iliac deep vein thromboses (DVT). The maternal PROCR 6936G allele was a mild risk factor for iliac DVT (OR = 5.5 [2.3-13.0]). The paternal PROCR 6936G allele was also a mild independent risk factor for iliac DVT (OR = 2.6 [1.1-6.2]) and only during pregnancy (rather than postpartum) among maternal carriers of the F5 1691A allele (OR = 77.6 [4.2 to > 999.9]). CONCLUSIONS: The paternal PROCR 6936G allele could be a risk factor for maternal iliac DVT. Its impact was milder than the F5 1691A and F2 20210A polymorphisms in mothers. We hypothesize that the prothrombotic effect of the paternal PROCR 6936G allele is localized. Therefore, DVT during pregnancy may be influenced by trophoblastic cell-surface proteins inherited from both maternal and paternal alleles.

Some hemostasis variables at the end of the population distributions are risk factors for severe postpartum hemorrhages.

BACKGROUND: Severe postpartum hemorrhages (PPH) represent a significant cause of maternal morbidity/mortality, but little is known about its hemostasis-related risk factors. Among the 32 463 women enrolled in the NOHA First cohort, 317 developed severe PPH (S-PPH group), 1269 non-severe PPH (NS-PPH group) and the remaining individuals were considered as control women (C group). METHODS: We performed a case-control study, including 317 triplets of women allocated from the three groups that shared the same clinical characteristics as the S-PPH group. RESULTS: From values obtained 6-9 months after delivery, low (but not-deficient) levels of fibrinogen, von Willebrand factor (VWF) antigen, factor (F) XI, platelet CD42b, TRAP-induced increase of platelet CD41a and high values of serum residual prothrombin activity or closure aperture times using the collagen-ADP cartridge on the PFA-100 system, and blood group O, were independently associated with a significant risk of severe PPH. Being positive for at least two of these eight variables was found in 1.6%, 3.5% and 20.8% of the women from the C, the NS-PPH and the S-PPH groups, respectively, the odds ratio for S-PPH in such a case being 16.4, 95%CI (6.5-41), P < 0.0001. CONCLUSIONS: Women with some hemostasis-related variables at the low or high end of the population distributions are prone to the severe forms of PPH. Clinical trials will allow us to know if acting on these risk factors can lower the clinical severity of PPH.