Serious complications and recurrences after pelvic organ prolapse surgery for 2309 women in the VIGI-MESH registry.

OBJECTIVE: To assess the incidence of serious complications and reoperations for recurrence after surgery for pelvic organ prolapse (POP) and compare the three most common types of repair. DESIGN: Prospective cohort study using a registry. SETTING: Nineteen French surgical centres. POPULATION: A total of 2309 women participated between 2017 and 2019. METHODS: A multivariate analysis including an inverse probability of treatment weighting approach was used to obtain three comparable groups. MAIN OUTCOME MEASURES: Serious complications and subsequent reoperations for POP recurrence. RESULTS: The median follow-up time was 17.6 months. Surgeries were native tissue vaginal repairs (n = 504), transvaginal mesh placements (n = 692) and laparoscopic sacropexies with mesh (n = 1113). Serious complications occurred among 52 women (2.3%), and reoperation for POP recurrence was required for 32 women (1.4%). At 1 year the cumulative weighted incidence of serious complications was 1.8% for native tissue vaginal repair, 3.9% for transvaginal mesh and 2.2% for sacropexy, and the rates for reoperation for recurrence of POP were 1.5, 0.7 and 1.1%, respectively. Compared with native tissue vaginal repair, the risk of serious complications was higher in the transvaginal mesh group (weighted hazard ratio, wHR 3.84, 95% CI 2.43-6.08) and the sacropexy group (wHR 2.48, 95% CI 1.45-4.23), whereas the risk of reoperation for prolapse recurrence was lower in both the transvaginal mesh (wHR 0.22, 95% CI 0.13-0.39) and sacropexy (wHR 0.29, 95% CI 0.18-0.47) groups. CONCLUSIONS: Our results suggest that native tissue vaginal repairs have the lowest risk of serious complications but the highest risk of reoperation for recurrence. These results are useful for informing women and for shared decision making. TWEETABLE ABSTRACT: Laparoscopic sacropexy had fewer serious complications than transvaginal mesh and fewer reoperations for recurrence than vaginal repair.

Type I interferon response and vascular alteration in chilblain-like lesions during the COVID-19 outbreak.

BACKGROUND: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. OBJECTIVES: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus. METHODS: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included. RESULTS: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL. CONCLUSIONS: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.

A workflow for 3D-CLEM investigating liver tissue.

Correlative light and electron microscopy (CLEM) is a method used to investigate the exact same region in both light and electron microscopy (EM) in order to add ultrastructural information to a light microscopic (usually fluorescent) signal. Workflows combining optical or fluorescent data with electron microscopic images are complex, hence there is a need to communicate detailed protocols and share tips & tricks for successful application of these methods. With the development of volume-EM techniques such as serial blockface scanning electron microscopy (SBF-SEM) and Focussed Ion Beam-SEM, correlation in three dimensions has become more efficient. Volume electron microscopy allows automated acquisition of serial section imaging data that can be reconstructed in three dimensions (3D) to provide a detailed, geometrically accurate view of cellular ultrastructure. In addition, combining volume-EM with high-resolution light microscopy (LM) techniques decreases the resolution gap between LM and EM, making retracing of a region of interest and eventual overlays more straightforward. Here, we present a workflow for 3D CLEM on mouse liver, combining high-resolution confocal microscopy with SBF-SEM. In this workflow, we have made use of two types of landmarks: (1) near infrared laser branding marks to find back the region imaged in LM in the electron microscope and (2) landmarks present in the tissue but independent of the cell or structure of interest to make overlay images of LM and EM data. Using this approach, we were able to make accurate 3D-CLEM overlays of liver tissue and correlate the fluorescent signal to the ultrastructural detail provided by the electron microscope. This workflow can be adapted for other dense cellular tissues and thus act as a guide for other three-dimensional correlative studies. LAY DESCRIPTION: As cells and tissues exist in three dimensions, microscopy techniques have been developed to image samples, in 3D, at the highest possible detail. In light microscopy, fluorescent probes are used to identify specific proteins or structures either in live samples, (providing dynamic information), or in fixed slices of tissue. A disadvantage of fluorescence microscopy is that only the labeled proteins/structures are visible, while their cellular context remains hidden. Electron microscopy is able to image biological samples at high resolution and has the advantage that all structures in the tissue are visible at nanometer (10-9 m) resolution. Disadvantages of this technique are that it is more difficult to label a single structure and that the samples must be imaged under high vacuum, so biological samples need to be fixed and embedded in a plastic resin to stay as close to their natural state as possible inside the microscope. Correlative Light and Electron Microscopy aims to combine the advantages of both light and electron microscopy on the same sample. This results in datasets where fluorescent labels can be combined with the high-resolution contextual information provided by the electron microscope. In this study we present a workflow to guide a tissue sample from the light microscope to the electron microscope and image the ultra-structure of a specific cell type in the liver. In particular we focus on the incorporation of fiducial markers during the sample preparation to help navigate through the tissue in 3D in both microscopes. One sample is followed throughout the workflow to visualize the important steps in the process, showing the final result; a dataset combining fluorescent labels with ultra-structural detail.

Complications after pelvic floor repair surgery (with and without mesh): short-term incidence after 1873 inclusions in the French VIGI-MESH registry.

OBJECTIVE: To assess the short-term incidence of serious complications of surgery for urinary incontinence or pelvic organ prolapse. DESIGN: Prospective longitudinal cohort study using a surgical registry. SETTING: Thirteen public hospitals in France. POPULATION: A cohort of 1873 women undergoing surgery between February 2017 and August 2018. METHODS: Preliminary analysis of serious complications after a mean follow-up of 7 months (0-18 months), according to type of surgery. Surgeons reported procedures and complications, which were verified by the hospitals' information systems. MAIN OUTCOME MEASURES: Serious complication requiring discontinuation of the procedure or subsequent surgical intervention, life-threatening complication requiring resuscitation, or death. RESULTS: Fifty-two women (2.8%, 95% CI 2.1-3.6%) experienced a serious complication either during surgery, requiring the discontinuation of the procedure, or during the first months of follow-up, necessitating a subsequent reoperation. One woman also required resuscitation; no women died. Of 811 midurethral slings (MUSs), 11 were removed in part or totally (1.4%, 0.7-2.3%), as were two of 391 transvaginal meshes (0.5%, 0.1-1.6%), and four of 611 laparoscopically placed mesh implants (0.7%, 0.2-1.5%). The incidence of serious complications 6 months after the surgical procedure was estimated to be around 3.5% (2.0-5.0%) after MUS alone, 7.0% (2.8-11.3%) after MUS with prolapse surgery, 1.7% (0.0-3.8%) after vaginal native tissue repair, 2.8% (0.9-4.6%) after transvaginal mesh, and 1.0% (0.1-1.9%) after laparoscopy with mesh. CONCLUSIONS: Early serious complications are relatively rare. Monitoring must be continued and expanded to assess the long-term risk associated with mesh use and to identify its risk factors. TWEETABLE ABSTRACT: Short-term serious complications are rare after surgery for urinary incontinence or pelvic organ prolapse, even with mesh.

A systematic review of interventions and performance measures for antifungal stewardship programmes.

Objectives: Antifungal resistance is a significant and emerging threat. Stewardship programmes (SPs) have been proposed as an opportunity to optimize antifungal use. While examples of antifungal SP implementation have been recently described, there is yet to be an overview of interventions and their impacts on performance measures. Methods: We systematically reviewed published articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses check-list 2009. MEDLINE was searched using the term 'antifungal stewardship' on 15 February 2017. Eligible studies were those that described an antifungal SP and included an intervention and an evaluation of performance measures. Results: A total of 97 studies were identified and 14 were included. Only five studies reported an antifungal stewardship team composed of all the recommended members. The main intervention was the formulation of recommendations to change treatment (12 of 14). The main performance measure collected was antifungal consumption (10 of 14), followed by antifungal expenditure (7 of 14), adherence to therapeutic advice (4 of 14) and impact on mortality (4 of 14). Antifungal consumption was reduced by 11.8% to 71% and antifungal expenditure by as much as 50%. Adherence to therapeutic advice ranged from 40% to 88%, whereas antifungal SPs had no impact on mortality. Conclusions: All antifungal SPs had an impact, in particular on antifungal consumption and antifungal expenditure. Active intervention including a review of prescriptions seems to have more impact than implementation of treatment guidelines only. According to available published studies, antifungal consumption appears to be the most achievable performance measure to evaluate the impact of an antifungal SP.

Effect of parathyroidectomy on quality of life and non-specific symptoms in normocalcaemic primary hyperparathyroidism.

BACKGROUND: Normocalcaemic primary hyperparathyroidism (NcPHPT) is a new clinical entity being diagnosed increasingly among patients with mild primary hyperparathyroidism (PHPT). The aim of this study was to evaluate quality of life and non-specific symptoms before and after parathyroidectomy in patients with NcPHPT compared with those with hypercalcaemic mild PHPT (Hc-m-PHPT). METHODS: This was a prospective multicentre study of patients with mild PHPT from four university hospitals. Patients were evaluated before operation, and 3, 6 and 12 months after surgery for quality of life using the SF-36-v2® questionnaire, as well as for 25 non-specific symptoms. RESULTS: Before operation, the only statistically significant difference between the NcPHPT and Hc-m-PHPT groups was in the mean(s.d.) blood calcium level (2·54 versus 2·73 mmol; P < 0·001). At 1 year after surgery, the blood calcium level had improved significantly in both groups, with no significant difference between them. Quality of life improved significantly in each group compared with its preoperative score, with regard to the physical component summary (P = 0·040 and P = 0·016 respectively), whereas the mental component summary improved significantly in the Hc-m-PHPT group only (P = 0·043). Only two non-specific symptoms improved significantly in the NcPHPT group compared with nine in the Hc-m-PHPT group. CONCLUSION: Parathyroidectomy mildly improves quality of life and some non-specific symptoms in patients with NcPHPT.

Developing 3D SEM in a broad biological context.

When electron microscopy (EM) was introduced in the 1930s it gave scientists their first look into the nanoworld of cells. Over the last 80 years EM has vastly increased our understanding of the complex cellular structures that underlie the diverse functions that cells need to maintain life. One drawback that has been difficult to overcome was the inherent lack of volume information, mainly due to the limit on the thickness of sections that could be viewed in a transmission electron microscope (TEM). For many years scientists struggled to achieve three-dimensional (3D) EM using serial section reconstructions, TEM tomography, and scanning EM (SEM) techniques such as freeze-fracture. Although each technique yielded some special information, they required a significant amount of time and specialist expertise to obtain even a very small 3D EM dataset. Almost 20 years ago scientists began to exploit SEMs to image blocks of embedded tissues and perform serial sectioning of these tissues inside the SEM chamber. Using first focused ion beams (FIB) and subsequently robotic ultramicrotomes (serial block-face, SBF-SEM) microscopists were able to collect large volumes of 3D EM information at resolutions that could address many important biological questions, and do so in an efficient manner. We present here some examples of 3D EM taken from the many diverse specimens that have been imaged in our core facility. We propose that the next major step forward will be to efficiently correlate functional information obtained using light microscopy (LM) with 3D EM datasets to more completely investigate the important links between cell structures and their functions.

Delivery of tidal volume from four anaesthesia ventilators during volume-controlled ventilation: a bench study.

BACKGROUND: Tidal volume (V(T)) must be accurately delivered by anaesthesia ventilators in the volume-controlled ventilation mode in order for lung protective ventilation to be effective. However, the impact of fresh gas flow (FGF) and lung mechanics on delivery of V(T) by the newest anaesthesia ventilators has not been reported. METHODS: We measured delivered V(T) (V(TI)) from four anaesthesia ventilators (Aisys™, Flow-i™, Primus™, and Zeus™) on a pneumatic test lung set with three combinations of lung compliance (C, ml cm H2O(-1)) and resistance (R, cm H2O litre(-1) s(-2)): C60R5, C30R5, C60R20. For each CR, three FGF rates (0.5, 3, 10 litre min(-1)) were investigated at three set V(T)s (300, 500, 800 ml) and two values of PEEP (0 and 10 cm H2O). The volume error = [(V(TI) - V(Tset))/V(Tset)] ×100 was computed in body temperature and pressure-saturated conditions and compared using analysis of variance. RESULTS: For each CR and each set V(T), the absolute value of the volume error significantly declined from Aisys™ to Flow-i™, Zeus™, and Primus™. For C60R5, these values were 12.5% for Aisys™, 5% for Flow-i™ and Zeus™, and 0% for Primus™. With an increase in FGF, absolute values of the volume error increased only for Aisys™ and Zeus™. However, in C30R5, the volume error was minimal at mid-FGF for Aisys™. The results were similar at PEEP 10 cm H2O. CONCLUSIONS: Under experimental conditions, the volume error differed significantly between the four new anaesthesia ventilators tested and was influenced by FGF, although this effect may not be clinically relevant.

Mechanical ventilation during cardiopulmonary resuscitation: influence of positive end-expiratory pressure and head-torso elevation.

BACKGROUND: Efficient ventilation is important during cardiopulmonary resuscitation (CPR). Nevertheless, there is insufficient knowledge on how the patient's position affects ventilatory parameters during mechanically assisted CPR. We studied ventilatory parameters at different positive end-expiratory pressure (PEEP) levels and when using an inspiratory impedance valve (ITD) during horizontal and head-up CPR (HUP-CPR). METHODS: In this human cadaver experimental study, we measured tidal volume (VT) and pressure during CPR at different randomized PEEP levels (0, 5 or 10 cmH2O) or with an ITD. CPR was performed, in the following order: horizontal (FLAT), at 18° and then at 35° head-thorax elevation. During the inspiratory phase we measured the net tidal volume (VT) adjusted to predicted body weight (VTPBW), reversed airflow (RAF), and maximum and minimum airway pressure (Pmax and Pmin). RESULTS: Using ten thawed fresh-frozen cadavers we analyzed the inspiratory phase of 1843 respiratory cycles, 229 without CPR and 1614 with CPR. In a mixed linear model, thoracic position and PEEP significantly impacted VTPBW (p < 0.001 for each), and the insufflation time, thoracic position and PEEP significantly affected the RAF (p < 0.001 for each) and Pmax (p < 0.001). For Pmin, only PEEP was significant (p < 0.001). In subgroup analysis, at 35° VTPBW and Pmax were significantly reduced compared with the flat or 18° position. CONCLUSION: When using mechanical ventilation during CPR, it seems that the PEEP level and patient position are important determinants of respiratory parameters. Moreover, tidal volume seems to be lower when the thorax is positioned at 35°.

Experimentally-guided development of a sensor for pleural cavity pressure sensing.

The precise monitoring of the intrapleural pressures, necessitates the development of a specific instrumental approach to select the correct shape, dimensions and material to implement the sensing balloon which will be inserted into the pleural cavity. We demonstrate that a 10 cm diameter disk, printed with filaments of TPU (Thermoplastic polyurethane) with hardness 92A offers the best compromise in terms of static sensitivity (0.28 mV/cmHg) and dynamic frequency response (48 Hz).

Design and automation of specific geometric quality controls for cone-radiosurgery treatments.

PURPOSE: The Varian TrueBeam STx linac can be equipped with BrainLAB stereotactic cones and ExacTrac imaging system for SRS treatments. However, these two third-party systems lack integration in a self-performance diagnosis tool dedicated to the SRS platform. The aim of this work was to design and automate essential geometric tests considering the complete set of cones with diameter range from 4 to 15 mm. METHODS: EPID-based tests were focused on the cone alignment, the radiation isocentricity and the isocenters congruence. Images acquired with or without the BrainLAB pointer were analysed using the Hough transform and morphological filtering operations, after assessment of the algorithm accuracy using simulated images. The new Machine QA program was experimented over one year. RESULTS: A subpixel resolution of 0.02 mm was found for the circular-field center detection algorithm. The tests results did not depend on the pointer location. The maximum deviations reported were in accordance with the AAPM SRS guidelines. The accurate localization of the linac radiation isocenter allowed for guidance of the ExacTrac calibration. A misalignment reaching 0.2 mm was measured for all cones but one, highlighting the benefit of systematizing this control before each patient SRS treatment. CONCLUSION: An effective in-house QA program dedicated to SRS cones was developed to supplement the standard machine performance check on our mixed SRS platform. Specific geometric tests even include the smallest 4-mm cone, which could be of great interest for future clinical indications such as the radiosurgery of functional disorders.

[Telomeres and lung]. / Télomères et poumon.

Genetic studies of familial forms of interstitial lung disease (ILD) have led to the discovery of telomere-related gene (TRG) mutations (TERT, TERC, RTEL1, PARN, DKC1, TINF2, NAF1, NOP10, NHP2, ACD, ZCCH8) in approximately 30% of familial ILD forms. ILD patients with TRG mutation are also subject to extra-pulmonary (immune-hematological, hepatic and/or mucosal-cutaneous) manifestations. TRG mutations may be associated not only with idiopathic pulmonary fibrosis (IPF), but also with non-IPF ILDs, including idiopathic and secondary ILDs, such as hypersensitivity pneumonitis (HP). The presence of TRG mutation may also be associated with an accelerated decline of forced vital capacity (FVC) or poorer prognosis after lung transplantation, notwithstanding which, usual ILD treatments may be proposed. Lastly, patients and their relatives are called upon to reduce their exposure to environmental lung toxicity, and are likely to derive benefit from specific genetic counseling and pre-symptomatic genetic testing.

Adaptation of the gut pathobiont Enterococcus faecalis to deoxycholate and taurocholate bile acids.

Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. This bacterial species is subdominant in a healthy physiological state of the gut microbiota (eubiosis) in adults, but can become dominant and cause infections when the intestinal homeostasis is disrupted (dysbiosis). The relatively high concentrations of bile acids deoxycholate (DCA) and taurocholate (TCA) hallmark eubiosis and dysbiosis, respectively. This study aimed to better understand how E. faecalis adapts to DCA and TCA. We showed that DCA impairs E. faecalis growth and possibly imposes a continuous adjustment in the expression of many essential genes, including a majority of ribosomal proteins. This may account for slow growth and low levels of E. faecalis in the gut. In contrast, TCA had no detectable growth effect. The evolving transcriptome upon TCA adaptation showed the early activation of an oligopeptide permease system (opp2) followed by the adjustment of amino acid and nucleotide metabolisms. We provide evidence that TCA favors the exploitation of oligopeptide resources to fuel amino acid needs in limiting oligopeptide conditions. Altogether, our data suggest that the combined effects of decreased DCA and increased TCA concentrations can contribute to the rise of E. faecalis population during dysbiosis.

Three bedside techniques to quantify dynamic pulmonary hyperinflation in mechanically ventilated patients with chronic obstructive pulmonary disease.

BACKGROUND: Dynamic pulmonary hyperinflation may develop in patients with chronic obstructive pulmonary disease (COPD) due to dynamic airway collapse and/or increased airway resistance, increasing the risk of volutrauma and hemodynamic compromise. The reference standard to quantify dynamic pulmonary hyperinflation is the measurement of the volume at end-inspiration (Vei). As this is cumbersome, the aim of this study was to evaluate if methods that are easier to perform at the bedside can accurately reflect Vei. METHODS: Vei was assessed in COPD patients under controlled protective mechanical ventilation (7 ± mL/kg) on zero end-expiratory pressure, using three techniques in a fixed order: (1) reference standard (Veireference): passive exhalation to atmosphere from end-inspiration in a calibrated glass burette; (2) ventilator maneuver (Veimaneuver): measuring the expired volume during a passive exhalation of 45s using the ventilator flow sensor; (3) formula (Veiformula): (Vt × Pplateau)/(Pplateau - PEEPi), with Vt tidal volume, Pplateau is plateau pressure after an end-inspiratory occlusion, and PEEPi is intrinsic positive end-expiratory pressure after an end-expiratory occlusion. A convenience sample of 17 patients was recruited. RESULTS: Veireference was 1030 ± 380 mL and had no significant correlation with Pplateau (r2 = 0.06; P = 0.3710) or PEEPi (r2 = 0.11; P = 0.2156), and was inversely related with Pdrive (calculated as Pplateau -PEEPi) (r2 = 0.49; P = 0.0024). A low bias but rather wide limits of agreement and fairly good correlations were found when comparing Veimaneuver and Veiformula to Veireference. Vei remained stable during the study period (low bias 15 mL with high agreement (95% limits of agreement from - 100 to 130 mL) and high correlation (r2 = 0.98; P < 0.0001) between both measurements of Veireference). CONCLUSIONS: In patients with COPD, airway pressures are not a valid representation of Vei. The three techniques to quantify Vei show low bias, but wide limits of agreement.

Distinct patterns of circulating endothelial cells in pulmonary hypertension.

The respective abundance of circulating endothelial cells and endothelial progenitor cells may reflect the balance between vascular injury and repair. As pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can share features of pulmonary remodelling, we postulated that the two disorders might be associated with different types of pulmonary endothelial dysfunction. We studied 25 consecutive patients undergoing cardiac catheterisation for suspected pulmonary hypertension. Nine patients had PAH, nine had CTEPH, and seven had normal pulmonary arterial pressure and served as controls. Circulating endothelial cells were isolated with CD146-coated beads. CD34(+)CD133(+) cell and endothelial progenitor cell numbers were respectively determined by flow cytometry and cell culture, in peripheral vein and pulmonary artery blood. Plasma levels of soluble vascular endothelial growth factor (VEGF), soluble E-selectin and soluble vascular cell adhesion molecule (sVCAM) were measured by ELISA. No difference in progenitor counts or VEGF levels was found across the three groups. Compared to controls, circulating endothelial cell numbers were significantly increased in PAH but not in CTEPH, in keeping with the elevated soluble E-selectin and sVCAM levels found in PAH alone. In conclusion, PAH, in contrast to CTEPH, is associated with markers of vascular injury (circulating endothelial cells, soluble E-selectin and sVCAM) but not with markers of remodelling (endothelial progenitor cells, CD34(+)CD133(+) cells and VEGF).

Pharmacology of capsaicin-, anandamide-, and N-arachidonoyl-dopamine-evoked cell death in a homogeneous transient receptor potential vanilloid subtype 1 receptor population.

BACKGROUND: Transient receptor potential vanilloid subtype 1 (TRPV1) receptor is a primary pain-sensing relay at peripheral sensory nerve endings and is also widespread in the brain, where it is implicated in neurodegeneration. Previous studies of TRPV1 neurotoxicity have utilized heterogeneous receptor populations, non-selective ligands, or non-neuronal cell types. Here, we explored the pharmacology of TRPV1-induced cytotoxicity in a homogeneous, neurone-like cellular environment. METHODS: Cell death was examined in a human neurone-like cell line, stably expressing recombinant human TRPV1. Cytotoxicity was quantified in terms of nuclear morphology and mitochondrial complex II activity. Immunocytochemical markers of apoptotic cell death were also examined. RESULTS: The TRPV1-selective agonist capsaicin, and the endovanilloids anandamide and N-arachidonoyl-dopamine (NADA), induced TRPV1-dependent delayed cell death in a concentration- and time-dependent manner. Capsaicin exposure time was significantly correlated with potency (r(2)=0.91, P=0.01). Release of cytochrome c from mitochondria, activation of caspase-3, and condensed nuclear chromatin were evident 6 h after capsaicin exposure, but cytotoxicity was unaffected by a pan-caspase inhibitor (zVAD-fmk, 50 microM). CONCLUSIONS: We conclude that capsaicin, anandamide, and NADA can initiate TRPV1-dependent delayed cell death in neurone-like cells. This is an apoptosis-like process, but independent of caspase activity.

Extended measures for controlling an outbreak of VIM-1 producing imipenem-resistant Klebsiella pneumoniae in a liver transplant centre in France, 2003-2004.

We report the successful control of an outbreak caused by imipenem-resistant VIM-1-producing Klebsiella pneumoniae (IR-Kp) in France. This outbreak occurred in a care centre for abdominal surgery that includes a 15-bed liver intensive care unit and performs more than 130 liver transplantations per year. The index case was a patient with acute liver failure transferred from a hospital in Greece for urgent liver transplantation who was carrying IR-Kp at admission as revealed by routine culture of a rectal swab. Infection control measures were undertaken and included contact isolation and promotion of hand hygiene with alcohol-based hand rub solution. Nevertheless, secondary IR-Kp cases were identified during the six following months from 3 December 2003 to 2 June 2004. From 2 June to 21 October, extended infection control measures were set up, such as cohorting IR-Kp carriers, contact patients and new patients in distinct sections with dedicated staff, limiting ward admission, and strict control of patient transfer. They led to a rapid control of the outbreak. The global attack rate of the IR-Kp outbreak was 2.5%, 13% in liver transplant patients and 0.4% in the other patients in the care centre (p<0.005). Systematic screening for IR-Kp of all patients admitted to the care centre is still maintained to date and no secondary IR-Kp case has been detected since 2 June 2004.

Piglets vocally express the anticipation of pseudo-social contexts in their grunts.

Emotions not only arise in reaction to an event but also while anticipating it, making this context a means of accessing the emotional value of events. Before now, anticipatory studies have rarely considered whether vocalisations carry information about emotional states. We studied both the grunts of piglets and their spatial behaviour as they anticipated two (pseudo)social events known to elicit positive emotions of different intensity: arrival of familiar conspecifics and arrival of a familiar human. Piglets spatially anticipated both pseudo-social contexts, and the spectro temporal features of grunts differed according to the emotional context. Piglets produced low-frequency grunts at a higher rate when anticipating conspecifics compared to anticipating a human. Spectral noise increased when piglets expected conspecifics, whereas the duration and frequency range increased when expecting a human. When the arrival of conspecifics was delayed, the grunt duration increased, whereas when the arrival of the human was delayed, the spectral parameters were comparable to those during isolation. This shows that vocal expressions in piglets during anticipation are specific to the expected reward. Vocal expressions-both their temporal and spectral features- are thus a good way to explore the emotional state of piglets during the anticipation of challenging events.

Comparison of pleural and esophageal pressure in supine and prone positions in a porcine model of acute respiratory distress syndrome.

Patients with moderate to severe acute respiratory distress syndrome (ARDS) benefit from prone positioning. Although the accuracy of esophageal pressure (Pes) to estimate regional pleural pressure (Ppl) has previously been assessed in the supine position, such data are not available in the prone position in ARDS. In six anesthetized, paralyzed, and mechanically ventilated female pigs, we measured Pes and Ppl into dorsal and ventral parts of the right pleural cavity. Airway pressure (Paw) and flow were measured at the airway opening. Severe ARDS [arterial partial pressure of oxygen ([Formula: see text])/fraction of inspired oxygen ([Formula: see text]) < 100 mmHg at positive end-expiratory pressure (PEEP) of 5 cmH2O] was induced by surfactant depletion. In supine and prone positions assigned in a random order, PEEP was set to 20, 15, 10, and 5 cmH2O and static end-expiratory chest wall pressures were measured from Pes (PEEPtot,es) and dorsal (PEEPtot,PplD) and ventral (PEEPtot,PplV) Ppl. The magnitude of the difference between PEEPtot,es and PEEPtot,PplD was similar in each position [-3.6 cmH2O in supine vs. -3.8 cmH2O in prone at PEEP 20 cmH2O (PEEP 20)]. The difference between PEEPtot,es and PEEPtot,PplV became narrower in the prone position (-8.3 cmH2O supine vs. -3.0 cmH2O prone at PEEP 20). PEEPtot,PplV was overestimated by Pes in the prone position at higher pressures. The median (1st-3rd quartiles) dorsal-to-ventral Ppl gradient was 4.4 (2.4-6.8) cmH2O in the supine position and -1.5 (-3.5 to +1.1) cmH2O in the prone position (P < 0.0001) and marginally influenced by PEEP (P = 0.058). Prone position narrowed end-expiratory dorsal-to-ventral Ppl vertical gradient, likely because of a more even distribution of mechanical forces over the chest wall.NEW & NOTEWORTHY In a porcine model of acute respiratory distress syndrome, we found that static end-expiratory esophageal pressure did not change significantly in prone position compared with supine position at any positive end-expiratory pressure (PEEP) tested between 5 and 20 cmH2O. Prone position was associated with an increased ventral pleural pressure and reduced end-expiratory dorsal-to-ventral pleural pressure (Ppl) vertical gradient, likely due to a more even distribution of mechanical forces over the chest wall.

Evaluation of teleconsultation system in the urological patient during the COVID-19 pandemic. / Evaluación de la teleconsulta en el paciente urológico durante la pandemia COVID-19.

INTRODUCTION: The global pandemic of COVID-19 has led to rapid implementation of telemedicine, but there is little information on patient satisfaction of this system as an alternative to face-to-face care. OBJECTIVE: To evaluate urological patient satisfaction with teleconsultation during the COVID-19 pandemic. MATERIAL AND METHODS: Observational, prospective, cross-sectional, non-interventional study carried out by telephone survey during the period considered as the peak of the pandemic (March-April 2020). A quality survey composed of 11 questions on urological care provided by physicians during the COVID-19 pandemic was conducted, selecting a representative sample of patients attended by teleconsultation. RESULTS: Two hundred patients were contacted by telephone to answer a survey on the quality of teleconsultation. The distribution of patients surveyed among the specialized consultations was homogeneous with the number of consultations cited in the period; 18% of them required assistance from family members. Sixty percent of patients avoided going to a medical center during the pandemic. Of the surveyed patients, 42% had cancelled diagnostic tests, 59% had cancelled medical consultations, 3.5% had cancelled treatments and 1% had cancelled interventions. Ten percent reported a worsening of urological symptoms during confinement. According to physicians, consultations were effectively delivered in 72% of cases, with teleconsultation being carried out by their usual urologist in 81%. Teleconsultation overall satisfaction level was 9 (IQI8-10), and 61.5% of respondents consider teleconsultation as a «health care option¼ after the healthcare crisis. CONCLUSION: Teleconsultation has been evaluated with a high level of satisfaction during the COVID-19 pandemic, offering continuous care to urological patients during the healthcare crisis. The perceived quality offers a field of optional telematic assistance in selected patients, which should be re-evaluated in a period without confinement measures.