A municipal health center's co-constructed therapeutic patient education program for patients with single or multiple morbidities / Co-construction d'un dispositif d'ETP mono et polypathologique dans un centre municipal de santé

Introduction: The accessibility of Therapeutic Patient Education (TPE) is essential to reduce social inequalities and to meet the challenges posed by the increase in chronic diseases. In France, the distribution of TPE throughout the territory is heterogeneous and patients still lack sufficient access. With these perspectives in mind, a municipal health center has developed an innovative TPE device by involving concerned patients from the outset. Objectives: The objectives of this article are to present the methodology implemented to co-construct a TPE program for patients with one or more prevalent diseases in the territory, as well as the results of the co-construction. Methods: Creation of a project team with various actors: patients, health professionals, administrators, researchers. Organization of synchronous and asynchronous times. Results: Four meetings and numerous exchanges made it possible to: define the common values and operating rules of the project team, reflect on the coordination of the care pathway, identify the specific and shared needs of patients affected by type 2 diabetes, arterial hypertension and/or obesity, agree on the principles of the device. Conclusion: The advantages of this device were discussed: flexible organization with numerous links with local actors, development of partnerships, expansion of the population concerned. Questions and difficulties were encountered, such as the coordination of actors and the representation of partner patients for the targeted diseases. This device will be tested and evaluated, mainly with an objective of improving it.

Introduction: L'accessibilité de l'Éducation Thérapeutique du Patient (ETP) est essentielle pour contribuer à une réduction des inégalités sociales et répondre aux défis posés par l'accroissement des maladies chroniques. En France, la répartition de l'offre d'ETP sur le territoire est inhomogène et les patients y occupent une place encore trop modeste. Dans ces perspectives, un centre municipal de santé a élaboré un dispositif innovant d'ETP en impliquant, dès le début, des patients concernés. Objectifs: Les objectifs de cet article sont de présenter la méthodologie mise en œuvre pour co-construire un dispositif d'ETP pour des patients porteurs d'une ou de plusieurs maladies prévalentes sur le territoire, ainsi que les résultats de la co-construction. Méthodes: Constitution d'une équipe projet avec divers acteurs : patients, professionnels de santé, administratifs, chercheurs. Organisation de temps synchrones et asynchrones. Résultats: Quatre réunions et de nombreux échanges ont permis de : définir les valeurs communes et les règles de fonctionnement de l'équipe projet, réfléchir sur la coordination du parcours de soins, identifier des besoins propres et partagés des patients touchés par le diabète de type 2, l'hypertension artérielle et/ou l'obésité, se mettre d'accord sur les principes du dispositif. Conclusion: Ce dispositif présente des avantages certains : organisation souple avec de nombreux liens avec les acteurs locaux, développement du partenariat, élargissement de la population concernée. Néanmoins, des questionnements et des difficultés ont été rencontrés comme la coordination des acteurs et la représentation des patients partenaires pour les maladies ciblées. Ce dispositif sera expérimenté et évalué principalement en vue de son amélioration.

Sublesional fat grafting leads to a temporary improvement of wound healing in chronic leg ulcers: A prospective, randomised clinical trial.

Chronic wounds remain a therapeutic and financial challenge for physicians and the health care systems. Innovative, inexpensive and effective treatment methods would be of immense value. The sublesional fat grafting could be such treatment, although effectiveness and safety have only been assessed in a few randomised clinical trials. The fat graft was obtained by liposuction, washed with the Coleman method and then injected sublesional and into the wound margins after surgical debridement. For the control group, saline solution was used instead of fat. The primary endpoint was to determine the wound size reduction in both groups. The wounds were measured preoperatively, intraoperatively and 3, 7, 21 and 60 days after the intervention. A p-value of <0.05 was considered significant. Furthermore, histology and microbiology of the wounds and pain were assessed. A temporary effect of the treatment was observed after 14 and 21 days. The wound size reduction was significantly larger in the intervention group, whereas after 60 days, no significant difference was detected between both groups. No adverse events could be reported and the pain level was almost equal in the control and intervention group. Sublesional fat grafting temporarily enhanced healing of chronic wounds. The procedure was safe and the pain level was low. Repeated interventions could lead to complete wound closure, which should be determined in future studies.

Causes of death and comorbidities in hospitalized patients with COVID-19.

Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19.

The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.

Synergistic effects of microbial anaerobic dechlorination of perchloroethene and nano zero-valent iron (nZVI) - A lysimeter experiment.

Perchloroethene (PCE) is a hazardous and persistent groundwater pollutant. Both treatment with nanoscaled zero-valent iron (nZVI) and biological degradation by bacteria have downsides. Distribution of nZVI underground is difficult and a high percentage of injected nZVI is consumed by anaerobic corrosion, forming H2 rather than being available for PCE dechlorination. On the other hand, microbial PCE degradation can suffer from the absence of H2. This can cause the accumulation of the hazardous metabolites cis-1,2-dichloroethene (DCE) or vinylchloride (VC). The combination of chemical and biological PCE degradation is a promising approach to overcome the disadvantages of each method alone. In this lysimeter study, artificial aquifers were created to test the influence of nZVI on anaerobic microbial PCE dechlorination by a commercially available culture containing Dehalococcoides spp. under field-like conditions. The effect of the combined treatment was investigated with molasses as an additional electron source and after cessation of molasses addition. The combination of nZVI and the Dehalococcoides spp. containing culture led to a PCE discharge in the lysimeter outflow that was 4.7 times smaller than that with nZVI and 1.6 times smaller than with bacterial treatment. Moreover, fully dechlorinated end-products showed an 11-fold increase compared to nZVI and a 4.2-fold increase compared to the microbial culture. The addition of nZVI to the microbial culture also decreased the accumulation of hazardous metabolites by 1.7 (cis-DCE) and 1.2 fold (VC). The stimulatory effect of nZVI on microbial degradation was most obvious after the addition of molasses was stopped.

Kramers-Kronig detection of four 20 Gbaud 16-QAM channels using Kerr combs for a shared phase estimation.

We experimentally demonstrate Kramers-Kronig detection of four 20 Gbaud 16-quadrature-amplitude-modulated (QAM) channels after 50 km fiber transmission using two soliton Kerr combs as signal sources and local oscillators. The estimated carrier phase at the receiver for each of the channels is relatively similar due to the coherence between the frequency comb lines. The standard deviation of the estimated carrier phase difference of the channels is less than 0.08 rad after 50 km single-mode fiber (SMF) transmission. This enables the carrier phase recovery derived from one channel to be shared among multiple channels. In the back-to-back scenario, the bit error rate (BER) performance for shared carrier phase recovery shows an optical signal-to-noise ratio penalty of ${\sim}{0.5}\;{\rm dB}$∼0.5dB compared to the BER performance for carrier phase recovery when derived for each channel independently. BERs below the forward error correction threshold are achieved after 50 km SMF transmission with both independent and shared carrier phase recovery for four 20-Gbaud 16-QAM signals.

Reconfigurable optical generation of nine Nyquist WDM channels with sinc-shaped temporal pulse trains using a single microresonator-based Kerr frequency comb.

Sinc-shaped temporal pulse trains have a spectrally efficient, rectangular Nyquist spectrum. We demonstrate the simultaneous and reconfigurable optical generation of multiple Nyquist-shaped wavelength-division-multiplexed (WDM) channels having temporal sinc-shaped pulse trains as data carriers. The channels are generated through the insertion of coherent lines using cascaded continuous-wave amplitude modulation around the spectral lines of a microresonator-based Kerr optical frequency comb. For each of nine Kerr frequency comb lines, we insert sub-groups of uniform and coherent lines to generate nine WDM channels. The deviations from ideal Nyquist pulses for the nine channels at repetition rates of 6 and 2 GHz are between 4.2%-6.1% and 2%-4.5%, respectively. Each WDM channel is modulated with on-off keying (OOK) at 6 Gbit/s. In addition, we show the reconfigurability of this method by varying the number of WDM channels, the generated sinc-shaped pulse train repetition rates, the duration, and the number of zero-crossings.

Drug Repositioning Inferred from E2F1-Coregulator Interactions Studies for the Prevention and Treatment of Metastatic Cancers.

Metastasis management remains a long-standing challenge. High abundance of E2F1 triggers tumor progression by developing protein-protein interactions (PPI) with coregulators that enhance its potential to activate a network of prometastatic transcriptional targets. Methods: To identify E2F1-coregulators, we integrated high-throughput Co-immunoprecipitation (IP)/mass spectometry, GST-pull-down assays, and structure modeling. Potential inhibitors of PPI discovered were found by bioinformatics-based pharmacophore modeling, and transcriptome profiling was conducted to screen for coregulated downstream targets. Expression and target gene regulation was validated using qRT-PCR, immunoblotting, chromatin IP, and luciferase assays. Finally, the impact of the E2F1-coregulator complex and its inhibiting drug on metastasis was investigated in vitro in different cancer entities and two mouse metastasis models. Results: We unveiled that E2F1 forms coactivator complexes with metastasis-associated protein 1 (MTA1) which, in turn, is directly upregulated by E2F1. The E2F1:MTA1 complex potentiates hyaluronan synthase 2 (HAS2) expression, increases hyaluronan production and promotes cell motility. Disruption of this prometastatic E2F1:MTA1 interaction reduces hyaluronan synthesis and infiltration of tumor-associated macrophages in the tumor microenvironment, thereby suppressing metastasis. We further demonstrate that E2F1:MTA1 assembly is abrogated by small-molecule, FDA-approved drugs. Treatment of E2F1/MTA1-positive, highly aggressive, circulating melanoma cells and orthotopic pancreatic tumors with argatroban prevents metastasis and cancer relapses in vivo through perturbation of the E2F1:MTA1/HAS2 axis. Conclusion: Our results propose argatroban as an innovative, E2F-coregulator-based, antimetastatic drug. Cancer patients with the infaust E2F1/MTA1/HAS2 signature will likely benefit from drug repositioning.

E2F1 induces miR-224/452 expression to drive EMT through TXNIP downregulation.

Malignant melanoma is highly lethal due to its aggressive invasive properties and metastatic dissemination. The transcription factor E2F1 is crucial for melanoma progression through poorly understood mechanisms. Here, we show that the miR-224/miR-452 cluster is significantly increased in advanced melanoma and invasive/metastatic cell lines that express high levels of E2F1. miR-224/miR-452 expression is directly activated by E2F1 through transactivation of the GABRE gene. Ectopic expression of miR-224/miR-452 in less aggressive cells induces EMT and cytoskeletal rearrangements and enhances migration/invasion. Conversely, miR-224/miR-452 depletion in metastatic cells induces the reversal of EMT, inhibition of motility, loss of the invasive phenotype and an absence of lung metastases in mice. We identify the metastasis suppressor TXNIP as new target of miR-224/miR-452 that induces feedback inhibition of E2F1 and show that miR-224/452-mediated downregulation of TXNIP is essential for E2F1-induced EMT and invasion. The E2F1-miR-224/452-TXNIP axis constitutes a molecular signature that predicts patient survival and may help to set novel therapies.

Calcified myocardial necrosis in pediatric patients after cardiopulmonary resuscitation.

We report three autopsy cases of wide-spread myocardial necrosis with calcification in pediatric patients after temporary generalized hypoxia and initially successful cardiopulmonary resuscitation, but subsequent in-hospital death. Autopsy and histological workup in all three cases showed multiple circumscribed calcified and necrotic areas in progressive stages of organization within the myocardium. We conclude that these macro- and microscopic autopsy features appear to be related to reperfusion injuries in children as a consequence of hypoxic-ischemic changes occurring in the peri- and postresuscitation period.

Correlation-based smoothing model for optical polishing.

A generalized model is developed to quantitatively describe the smoothing effects from different polishing tools used for optical surfaces. The smoothing effect naturally corrects mid-to-high spatial frequency errors that have features small compared to the size of the polishing lap. The original parametric smoothing model provided a convenient way to compare smoothing efficiency of different polishing tools for the case of sinusoidal surface irregularity, providing the ratio of surface improvement via smoothing to the bulk material removal. A new correlation-based smoothing model expands the capability to quantify smoothing using general surface data with complex irregularity. For this case, we define smoothing as a band-limited correlated component of the change in the surface and original surface. Various concepts and methods, such as correlation screening, have been developed and verified to manipulate the data for the calculation of smoothing factor. Data from two actual polishing runs from the Giant Magellan Telescope off-axis segment and the Large Synoptic Survey Telescope monolithic primary-tertiary mirror were processed, and a quantitative evaluation for the smoothing efficiency of a large pitch lap and a conformal lap with polishing pads is provided.

Fatal spontaneous subdural bleeding due to neonatal giant cell hepatitis: a rare differential diagnosis of shaken baby syndrome.

A 7-week-old girl showed vomiting after feeding, facial pallor, loss of muscle tone and respiratory depression. An emergency doctor performed successful resuscitation and after arrival in hospital, cranial ultrasound showed left-sided subdural hemorrhage, cerebral edema with a shift of the midline, and a decrease in cerebral perfusion. Ophthalmologic examination showed retinal hemorrhage. In view of this, the doctors suspected shaken baby syndrome and approached the parents with their suspicions, but they denied any shaking or trauma. Despite surgery for the subdural hemorrhage the girl died a few hours later with a severe coagulopathy. Autopsy verified subdural hemorrhage, cerebral edema and retinal hemorrhage, but also revealed intact bridging veins and a lack of optic nerve sheath hemorrhage, therefore shaken baby syndrome could not be proven by autopsy. Histological examination showed severe neonatal giant cell hepatitis as the cause of the severe coagulopathy and the associated spontaneous subdural bleeding. Neonatal giant cell hepatitis may be responsible for unexpected deaths in infancy and, although rarely associated with subdural bleeding, must be considered as a potential differential diagnosis of shaken baby syndrome.

Wavefront control of the large optics test and integration site (LOTIS) 6.5m collimator.

The LOTIS Collimator provides scene projection within a 6.5m diameter collimated beam used for optical testing research in air and vacuum. Diffraction-limited performance (0.4 to 5microm wavelength) requires active wavefront control of the alignment and primary mirror shape. A hexapod corrects secondary mirror alignment using measurements from collimated sources directed into the system with nine scanning pentaprisms. The primary mirror shape is controlled with 104 adjustable force actuators based on figure measurements from a center-of-curvature test. A variation of the Hartmann test measures slopes by monitoring the reflections from 36 small mirrors bonded to the optical surface of the primary mirror. The Hartmann source and detector are located at the f/15 Cassegrain focus. Initial operation has demonstrated a closed-loop 110 nm rms wavefront error in ambient air over the 6.5m collimated beam.

A sudden death with lung embolism after inadvertent infusion of zinc oxide shake lotion.

A 74-year old woman in postoperative treatment after a colonic surgery died immediately after perfusion of about 1.5 mL of a white emulsion which was believed to contain 1% propofol via cardiac catheter into the right atrium. It was strongly suspected that a syringe with a zinc oxide shake lotion (consisting of 20% ZnO, 20% talc, 25% glycerol and 35% water) which was intended for external treatment had been mistaken for the propofol syringe. During autopsy, an anatomic cause of death could not be found. In order to exclude an intoxication and to determine the significance of the perfusion fluid in this context, toxicological and histological investigations were performed. Propofol and other drugs applied to the patient were found in therapeutic or sub-therapeutic range. However, in comparison to a control case, the zinc concentrations determined by AAS were about 200 times higher in lung tissue, 10 times higher in heart blood and 3-4 times higher in kidney and liver tissue. No increase was seen in venous blood. Histology showed a strong embolism of the lung tissue with birefingent sharp-edged crystals, which were identified as the talcum, and an amorphous component (ZnO). The same embolism was seen to a medium extent also in the brain sections and to a low extent in heart, liver, pancreas and kidney. Pulmonary embolism by talcum and zinc oxide was established as the cause of death which occurred by syringe swap due to insufficient security precautions in the drug administration. The results are discussed in context of pulmonary microembolism cases frequently described for drug addicts after injection of crashed talcum containing tablets.

Thoracoscopic thymectomy in the treatment concept for myasthenia gravis.

Myasthenia gravis (MG) is a chronic autoimmune disease that usually responds positively to treatment with thymectomy. Standard surgical procedures have been shown to result in a beneficial outcome. This Chapter includes discussions regarding what are controversial, and opinions as to what constitutes the optimal access to be used for thymectomy. In a prospective study conducted between 8/97 and 12/03, 137 patients with MG underwent thoracoscopic thymectomy, for which a left-sided approach was generally applied. An analysis of the intraoperative and postoperative course was performed, as well as of the impact of the surgical procedure on further development of the disease. The results obtained were compared with those published in the literature, with particular reference to results obtained with open surgery. The patients in this study were 96 females and 41 males, with a mean age of 35.8 (range: 9-83) years. The mean preoperative duration of the disease was 22.9 (range: 1-140) months. In 8 (5.8%) patients, the procedure was converted to an anterolateral thoracotomy or sternotomy. The postoperative morbidity rate was 5.8%, one (0.7) patient died and the mean follow up was 24.7 (range: 1-57) months. Complete remission was noted in 19.4%, and improvements reflected either in a reduction in the medication required or a decrease in symptom severity, in a total of 76.8%. Complete thoracoscopic thymectomy is a technically feasible operation, equally as effective as conventional open surgery. Remissions or symptomatic improvements were observed in more than 70% of the patients. The low morbidity rate, coupled with excellent cosmetic results, have led to increasing acceptance of the operation both by patients and Neurologists. Therefore, thoracoscopic thymectomy represents a new, alternative method for use in patients with MG.