Epidemiology of fungal infection in COVID 19 in Spain during 2020 and 2021: a nationwide study.

We realize a nationwide population-based retrospective study to analyze the characteristics and risk factors of fungal co-infections in COVID-19 hospitalized patients as well as describe their causative agents in the Spanish population in 2020 and 2021. Data were obtained from records in the Minimum Basic Data Set of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health, and annually published with two years lag. The assessment of the risk associated with the development of healthcare-associated fungal co-infections was assessed using an adjusted logistic regression model. The incidence of fungal co-infection in COVID-19 hospitalized patients was 1.41%. The main risk factors associated were surgery, sepsis, age, male gender, obesity, and COPD. Co-infection was associated with worse outcomes including higher in-hospital and in ICU mortality, and higher length of stay. Candida spp. and Aspergillus spp. were the microorganisms more frequent. This is the first study analyzing fungal coinfection at a national level in hospitalized patients with COVID-19 in Spanish population and one of the few studies available that demonstrate that surgery was an independent risk factor of Aspergillosis coinfection in COVID-19 patients.

Double vitrification and warming does not compromise the chance of live birth after single unbiopsied blastocyst transfer.

STUDY QUESTION: Does double vitrification and thawing of an embryo compromise the chance of live birth after a single blastocyst transfer? SUMMARY ANSWER: The live birth rate (LBR) obtained after double vitrification was comparable to that obtained after single vitrification. WHAT IS KNOWN ALREADY: Double vitrification-warming (DVW) is commonly practiced to accommodate surplus viable embryos suitable for transfer, to allow retesting of inconclusively diagnosed blastocysts in preimplantation genetic testing (PGT), and to circumvent limitations associated with national policies on embryo culture in certain countries. Despite its popularity, the evidence concerning the impact of DVW practice on ART outcomes is limited and lacking credibility. This is the first thorough investigation of clinical pregnancy and LBR following DVW in the case where the first round of vitrification occurred at the zygote stage and the second round occurred at the blastocyst stage in the absence of biopsy. STUDY DESIGN SIZE DURATION: This is a retrospective observational analysis of n = 407 single blastocyst transfers whereby embryos created by IVF/ICSI were vitrified-warmed once (single vitrification-warming (SVW) n = 310) or twice (DVW, n = 97) between January 2017 and December 2021. PARTICIPANTS/MATERIALS SETTING METHODS: In the SVW group, blastocysts were vitrified on Day 5/6 and warmed on the day of embryo transfer (ET). In the DVW group, two pronuclear (2PN) zygotes were first vitrified-warmed and then re-vitrified on Day 5/6 and warmed on the day of ET. Exclusion criteria were ETs from PGT and vitrified-warmed oocyte cycles. All of the ETs were single blastocyst transfers performed at the University Hospital Zurich in Switzerland following natural or artificial endometrial preparation. MAIN RESULTS AND THE ROLE OF CHANCE: The biochemical pregnancy rate, clinical pregnancy rate (CPR), and LBR were all comparable between the DVW and SVW groups. The CPR for DVW was 44.3% and for SVW it was 42.3% (P = 0.719). The LBR for DVW was 30.9% and for SVW it was 28.7% (P = 0.675). The miscarriage rate was additionally similar between the groups: 27.9% for DVW and 32.1% for SVW groups (P = 0.765). LIMITATIONS REASONS FOR CAUTION: The study is limited by its retrospective nature. Caution should be taken concerning interpretation of these findings in cases where DVW occurs at different stages of embryo development. WIDER IMPLICATIONS OF THE FINDINGS: The result of the present study on DVW procedure provides a framework for counselling couples on their chance of clinical pregnancy per warming cycle. It additionally provides confidence and reassurance to laboratory professionals in certain countries where national policies limit embryo culture strategies making DVW inevitable. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the University Research Priority Program 'Human Reproduction Reloaded' of the University of Zurich. The authors have no conflict of interest related to this study to declare. TRIAL REGISTRATION NUMBER: N/A.

Higher miscarriage rate in subfertile women with endometriosis receiving unbiopsied frozen-warmed single blastocyst transfers.

Background: Assisted reproductive technology treatment is recommended to overcome endometriosis-associated infertility but current evidence is controversial. Endometriosis is associated with lower antral follicle count (AFC) and oocyte yield but similar clinical outcomes compared to controls. Unaffected ovarian stimulation response and embryological outcomes but lower clinical pregnancy and live birth rates and higher miscarriage rates have been reported, implying direct impact on endometrial receptivity. With evidence emerging on the benefit of frozen-warmed and blastocyst stage transfer, we investigated ART outcomes in endometriosis using homogeneous case-control groups. Methods: This is a retrospective observational case-control study including n = 66 frozen-warmed unbiopsied single blastocyst transfers of patients with endometriosis and n = 96 of women exhibiting idiopathic sterility. All frozen-warmed transfers followed artificial endometrial preparation. Results: In control women, the mean number of oocytes recovered at oocyte pick up was higher compared to women with endometriosis (15.3 ± 7.1 vs. 12.7 ± 5.2, p = 0.025) but oocyte maturation index (mature oocytes/total oocytes at oocyte pick up) was significantly higher for endometriosis (48.2% vs. 34.0%, p = 0.005). The same was shown for the subgroup of 44 endometriosis patients after endometrioma surgery when compared with controls (49.1% vs. 34.0%, p = 0.014). Clinical pregnancy rate was not higher in endometriosis but was close to significance (47.0% vs. 32.3%, p = 0.059) while live birth rate was comparable (27.3% vs. 32.3%, p = 0.746). Miscarriage rate was higher in the endometriosis group (19.7% vs. 7.3%, p = 0.018). A significantly higher AFC was observed in the control group in comparison with the endometriosis group (16.3 ± 7.6 vs. 13.4 ± 7.0, p = 0.014). Live birth rate did not differ when comparing all endometriosis cases (p = 0.746), ASRM Stage I/II and Stage III/IV (p = 0.348 and p = 0.888) with the control group but the overall pregnancy rate was higher in ASRM Stage I/II (p = 0.034) and miscarriage rate was higher in ASRM Stage III/IV (p = 0.030) versus control. Conclusion: Blastocyst transfers in women with endometriosis originate from cycles with lower AFC but higher share of mature oocytes than in control women, suggesting that endometriosis might impair ovarian reserve but not stimulation response. A higher miscarriage rate, independent of blastocyst quality may be attributed to an impact of endometriosis on the endometrium beyond the timing of implantation.

Epidemiology of bacterial co-infections and risk factors in COVID-19-hospitalized patients in Spain: a nationwide study.

BACKGROUND: We performed a nationwide population-based retrospective study to describe the epidemiology of bacterial co-infections in coronavirus disease 2019 (COVID-19)-hospitalized patients in Spain in 2020. We also analyzed the risk factors for co-infection, the etiology and the impact in the outcome. METHODS: Data were obtained from records in the Minimum Basic Data Set (MBDS) of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health and annually published with 2 years lag. COVID-19 circulated in two waves in 2020: from its introduction to 31st June and from 1st July to 31st December. The risk of developing a healthcare-associated bacterial co-infection and the risk for in-hospital and intensive care unit (ICU) mortality in co-infected patients was assessed using an adjusted logistic regression model. RESULTS: The incidence of bacterial co-infection in COVID-19 hospitalized patients was 2.3%. The main risk factors associated with bacterial co-infection were organ failure, obesity and male sex. Co-infection was associated with worse outcomes including higher in-hospital, in-ICU mortality and higher length of stay. Gram-negative bacteria caused most infections. Causative agents were similar between waves, although higher co-infections with Pseudomonas spp. were detected in the first wave and with Haemophilus influenzae and Streptococcus pneumoniae in the second. CONCLUSIONS: Co-infections are not as common as those found in other viral respiratory infections; therefore, antibiotics should be used carefully. Screening for actual co-infection to prescribe antibiotic therapy when required should be performed.

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Clinical course of neonatal acute kidney injury: multi-center prospective cohort study.

BACKGROUND: Neonatal acute kidney injury (AKI) has been associated with unfavorable outcomes, including increased mortality. We aimed to describe the clinical course and outcomes during the first 7 days after diagnosis in newborns with AKI in three neonatal intensive care units in Popayán-Colombia. METHODS: Multi-center prospective cohort study conducted between June 2019 and December 2020 in three NICUs after ethical approval. We included newborns between 2 and 28 days of life, first diagnosed with AKI using the KDIGO classification modified for newborns which consider increased serum creatinine values over baseline values as well as urine output over time in hours or both. Patients with chromosomal abnormalities, major kidney malformations, and complex congenital heart disease were excluded. Patients were followed for up to 7 days after diagnosis and the maximum KDIGO stage, recovery of kidney function, need for renal replacement therapy and cumulative incidence of death were evaluated. RESULTS: Over the 18 months of the study, 4132 newborns were admitted to the NICUs, and 93 patients (2.25, 95% CI 1.82-2.75%) developed neonatal AKI. 59.1% of the newborns were premature and there were no differences in severity according to gestational age. During follow-up, the maximum KDIGO was 64.5% for AKI-stage 1, 11.8% for AKI-stage 2, and 23.7% for AKI-stage 3. Kidney function recovery was higher in AKI-stage 1 patients vs. AKI-severe (AKI-stage 2 and 3) (95% vs. 48.5%). Five patients (5.4%) received renal replacement therapy and 15 died (16.1%), four in AKI-stage 1 vs. 11 in AKI-severe (6.7% vs 33.3%). CONCLUSIONS: Newborns admitted to the NICUs can develop AKI regardless of gestational age, and it is more frequent between the second and ninth days of life. More patients whit AKI-stage 1 recover and die less than those in a severe stage.

CariesCare International adapted for the pandemic in children: Caries OUT multicentre single-group interventional study protocol.

BACKGROUND: Comprehensive caries care has shown effectiveness in controlling caries progression and improving health outcomes by controlling caries risk, preventing initial-caries lesions progression, and patient satisfaction. To date, the caries-progression control effectiveness of the patient-centred risk-based CariesCare International (CCI) system, derived from ICCMS™ for the practice (2019), remains unproven. With the onset of the COVID-19 pandemic a previously planned multi-centre RCT shifted to this "Caries OUT" study, aiming to assess in a single-intervention group in children, the caries-control effectiveness of CCI adapted for the pandemic with non-aerosols generating procedures (non-AGP) and reducing in-office time. METHODS: In this 1-year multi-centre single-group interventional trial the adapted-CCI effectiveness will be assessed in one single group in terms of tooth-surface level caries progression control, and secondarily, individual-level caries progression control, children's oral-health behaviour change, parents' and dentists' process acceptability, and costs exploration. A sample size of 258 3-5 and 6-8 years old patients was calculated after removing half from the previous RCT, allowing for a 25% dropout, including generally health children (27 per centre). The single-group intervention will be the adapted-CCI 4D-cycle caries care, with non-AGP and reduced in-office appointments' time. A trained examiner per centre will conduct examinations at baseline, at 5-5.5 months (3 months after basic management), 8.5 and 12 months, assessing the child's CCI caries risk and oral-health behaviour, visually staging and assessing caries-lesions severity and activity without air-drying (ICDAS-merged Epi); fillings/sealants; missing/dental-sepsis teeth, and tooth symptoms, synthetizing together with parent and external-trained dental practitioner (DP) the patient- and tooth-surface level diagnoses and personalised care plan. DP will deliver the adapted-CCI caries care. Parents' and dentists' process acceptability will be assessed via Treatment-Evaluation-Inventory questionnaires, and costs in terms of number of appointments and activities. Twenty-one centres in 13 countries will participate. DISCUSSION: The results of Caries OUT adapted for the pandemic will provide clinical data that could help support shifting the caries care in children towards individualised oral-health behaviour improvement and tooth-preserving care, improving health outcomes, and explore if the caries progression can be controlled during the pandemic by conducting non-AGP and reducing in-office time. TRIAL REGISTRATION: Retrospectively-registered-ClinicalTrials.gov-NCT04666597-07/12/2020: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AGM4&selectaction=Edit&uid=U00019IE&ts=2&cx=uwje3h . Protocol-version 2: 27/01/2021.

Final analysis of the randomized trial on imatinib as an adjuvant in localized gastrointestinal stromal tumors (GIST) from the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), the Australasian Gastro-Intestinal Trials Group (AGITG), UNICANCER, French Sarcoma Group (FSG), Italian Sarcoma Group (ISG), and Spanish Group for Research on Sarcomas (GEIS)☆.

BACKGROUND: In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery in localized, high/intermediate-risk gastrointestinal stromal tumors (GIST) patients. Interim analysis results were published in 2015 upon recommendation from an independent data review committee. We report the final outcome of the study. PATIENTS AND METHODS: This was a randomized, open-label, multicenter phase III trial carried out at 112 hospitals in 12 countries. Patients were randomized to 2 years of imatinib, 400 mg daily, or no further therapy after surgery. The primary endpoint was imatinib failure-free survival (IFFS), while relapse-free survival (RFS), relapse-free interval (RFI), overall survival (OS) and toxicity were secondary endpoints. Adjusting for the interim analyses, results on IFFS were assessed on a 4.3% significance level; for the other endpoints, 5% was used. RESULTS: Nine hundred and eight patients were randomized between January 2005 and October 2008: 454 to imatinib and 454 to observation; 835 patients were eligible. With a median follow-up of 9.1 years, 5 (10)-year IFFS was 87% (75%) in the imatinib arm versus 83% (74%) in the control arm [hazard ratio (HR) = 0.87, 95.7% confidence interval (CI) (0.65; 1.15), P = 0.31]; RFS was 70% versus 63% at 5 years and 63% versus 61% at 10 years, [HR = 0.71, 95% CI (0.57; 0.89), P = 0.002]; OS was 93% versus 92% at 5 years and 80% versus 78% at 10 years [HR = 0.88, 95% CI (0.65; 1.21), P = 0.43]. Among 526 patients with high-risk GIST by local pathology, 10-year IFFS and RFS were 69% versus 61%, and 48% versus 43%, respectively. CONCLUSIONS: With 9.1 years of follow-up, a trend toward better long-term IFFS in imatinib-treated patients was observed in the high-risk subgroup. Although the difference was not statistically significant and the surrogacy value of such an endpoint is not validated, this may be seen as supporting the results reported by the Scandinavian/German trial, showing a sustained small but significant long-term OS benefit in high-risk GIST patients treated with 3 years of adjuvant imatinib.

Optimization of the Preanalytical Phase by Estimating Serum Indices Using an Automated Classifier.

BACKGROUND: Most laboratory errors occur in the preanalytical phase. Among the most common preanalytical errors are interferences due to hemolysis, lipemia, and icterus. Our objective was to evaluate a serum interference estimation methodology by the RSD classifier, to identify other biochemical parameters affected by preanalytical interferences, and to determine the economic impact of its implementation. METHODS: The serum indices of 65,529 requests measured by the RSD system and by the analytical determination on the Cobas 711 or Cobas 8000 platforms were collected. We proceeded to the search for association patterns between the serum indices and laboratory analytical tests using data mining techniques. The influence of the preanalytical interferences was evaluated in 91 laboratory tests that include biochemistry, immunoassay, and coagulation. The savings estimation after the implementation of this methodology was made by time series models. RESULTS: The evaluation of the generated model showed compatibilities between the methods used (94.4% accuracy). The implementation of a protocol for serum indices estimation by the RSD would avoid the unnecessary analysis of the tests which are affected by interferences, achieving an estimated annual savings of €10,561. In addition, it allowed the estimation of bilirubin values which would add an annual savings of €4,900 in our laboratory. On the other hand, data mining techniques have allowed us to identify the following laboratory tests affected by hemolysis which are not usually considered in laboratories: iron, transferrin, fibrinogen, and alkaline phosphatase. CONCLUSIONS: The RSD classifier is an efficient estimation method of serum indices and it allows the estimation of bilirubin values. The implementation of this methodology in our laboratory could lead to an estimated annual savings of more than €15,000 without increasing response times. Iron, alkaline phosphatase, transferrin, and fibrinogen should be included in the evaluated procedure.

Strong visible photoluminescence emission of ZnO nanosheets and nanoflowers by a facile hydrothermal route.

Zinc oxide nanostructures such as nanosheets (NS) and nanoflowers (NF) were obtained by a facile hydrothermal synthesis using zinc chloride (ZnCl2) as precursor with low molar concentrations and a short synthesis time (2 h) at 200 °C. By means of X-ray diffraction and Raman spectroscopy measurements, the wurtzite-type ZnO structure was confirmed with high crystalline quality. SEM micrographs showed the influence of ZnCl2 concentration on ZnO morphology; ZnO NF were obtained at low concentrations (0.02 and 0.05 M), while ZnO NS were seen for higher concentrations (0.2-0.6 M) and their thicknesses can be estimated from 15 to 60 nm. In addition, TEM images showed a large number of pores with sizes below 15 nm in both ZnO nanostructures. Raman and photoluminescence displayed the surface defects density for ZnO nanostructures. Raman spectra showed the E1(LO) mode localized at ∼581 cm-1, associated with oxygen vacancies and zinc interstitials, being more intense for ZnO NF, while photoluminescence results showed a strong yellow-orange emission (centered from 587 to 618 nm) relative to UV emission, being more intense for ZnO NF. These properties reveal further potential for high performance luminescent devices based on ZnO NF and NS.

[Massive rotator cuff injury: arthroscopic treatment with upper capsular reconstruction]. / Lesión masiva del manguito rotador: tratamiento artroscópico con reconstrucción capsular superior.

Massive rotator cuff injuries (LMMRs) are those breaks of more than 5 cm either the anteroposterior plane, or lateromedial plane. Some authors consider them to be complete ruptures of at least two rotator cuff tendons. The clinical case of a 63-year-old man with this type of injury that was resolved by the superior capsule reconstruction technique is presented, technical details and some of the literature review to carry out the procedure are shown.

Las lesiones masivas del manguito rotador (LMMR) son aquellas roturas de más de 5 cm ya sea el plano anteroposterior o lateromedial. Algunos autores las consideran como roturas completas de al menos dos tendones del maguito rotador. Se presenta el caso clínico de un varón de 63 años con este tipo de lesión que se resolvió mediante la técnica de reconstrucción de cápsula superior, se muestran detalles técnicos y un poco de la revisión de la literatura para llevar a cabo el procedimiento.

Expression of CD47 antigen in Reed-Sternberg cells as a new potential biomarker for classical Hodgkin lymphoma.

INTRODUCTION: CD47 over expression has been reported in several tumor subtypes. CD47 interacts with SIRPalpha on macrophages inhibiting phagocytic signal, providing a survival advantage to tumor. CD47, therefore, represents a valuable target for immunotherapy and is currently under clinical investigation. We aimed to study CD47 expression in Hodgkin Reed Sternberg cells (HRS). METHODS: We tested a polyclonal CD47 antibody (LifeSpan Biosciences, Seattle, WA) expression along with classical HRS cell markers on a tissue array of 16 classical Hodgkin Lymphoma (CHL) tumor biopsies obtained from newly diagnosed, non-selected patients (8 Female, 8 Male patients) in our institution from October 2016 to January 2018. Histologic subtypes were nodular sclerosis in 11 cases, mixed Cellularity in 3 cases and lymphocyte rich in 2 additional cases. Median age was 53 years (Range: 8, 74). Early stage disease was found in three patients without unfavorable prognostic factors according to EORTC and GHSG criteria, one patient with unfavorable prognostic factors and nine patients had advanced disease. Bulk disease was present in one patient. Normal lymphoid tissue and normal prostate epithelium were used as normal controls as recommended by manufacturer. Approval from the Local Ethical committee was obtained before any analysis. RESULTS: CD47 was overexpressed on all HRS cells with a characteristic dot-like pattern in 13/13 cases of CHL. HRS clearly expressed CD47 more intensely than infiltrating T and stromal cells. DISCUSSION: We propose that HRS cells, by up-regulating CD47, might avoid innate immunity check on tumor growth, which could be circumvented using blocking monoclonal antibodies.

Carcinoma adenoneuroendocrino mixto de la ampolla de Vater: reporte de caso / Mixed adenoneuroendocrine carcinoma of the ampulla of Vater: case report

INTRODUCCIÓN: Los carcinomas adenoneuroendocrinos mixtos (MANEC) son tipos de tumores bifásicos, reconocidos morfológicamente ante la presencia de una formación neoplásica constituida de manera simultánea por epitelio glandular y células neuroendocrinas. Dentro del tracto gastrointestinal, estas neoplasias predominan en el estómago o el colon. Solo 19 casos localizados en la ampolla de Vater han sido reportados por la literatura. OBJETIVO: Reportar un caso de MANEC; revisar la epidemiología, pronóstico y tratamiento de estos tumores. MATERIALES Y MÉTODO: Presentación de caso clínico de una paciente con diagnóstico de adenocarcinoma neuroendocrino mixto de la región ampular. DISCUSIÓN: La presentación clínica, el manejo y el pronóstico son similares al del adenocarcinoma ampular. Se diagnostican con el examen histopatológico de la muestra resecada. Ambos componentes deben ser histológicamente malignos, y cada uno de ellos debe representar al menos el 30% de la lesión. CONCLUSIÓN: Los MANEC ampulares son tumores poco comunes a nivel mundial, siendo éste el primer caso reportado en nuestro instituto.

INTRODUCTION: Mixed adenoneuroendocrine carcinomas (MANEC) are types of biphasic tumors, morphologically recognized in the presence of a neoplastic formation constituted simultaneously by glandular epithelium and neuroendocrine cells. Only 19 cases located in the ampulla of Vater have been reported in the literature. Within the gastrointestinal tract, these neoplasms predominate in the stomach or colon. AIM: Report a case of MANEC; review of the epidemiology, prognosis and treatment of these tumors. MATERIALS AND METHOD: Case presentation of a patient diagnosed with mixed adeno-neuroendocrine carcinoma of the ampullary region. DISCUSSION: The clinical presentation, management and prognosis are similar to ampullary adenocarcinoma. These tumors are diagnosed with a histopathological examination of the resected specimen. Both components must be histologically malignant, and each of them must represent at least 30% of the lesion. CONCLUSION: MANEC of the ampulla are rare tumors worldwide, being this case the first reported in our institute.

Diabetes, undernutrition, migration and indigenous communities: tuberculosis in Chiapas, Mexico.

We investigated the distribution of comorbidities among adult tuberculosis (TB) patients in Chiapas, the poorest Mexican state, with a high presence of indigenous population, and a corridor for migrants from Latin America. Secondary analysis on 5508 new adult TB patients diagnosed between 2010 and 2014 revealed that the most prevalent comorbidities were diabetes mellitus (DM; 19.1%) and undernutrition (14.4%). The prevalence of DM in these TB patients was significantly higher among middle aged (41-64 years) compared with older adults (⩾65 years) (38.6% vs. 23.2%; P < 0.0001). The prevalence of undernutrition was lower among those with DM, and higher in communities with high indigenous presence. Immigrants only comprised 2% of all TB cases, but were more likely to have unfavourable TB treatment outcomes (treatment failure, death and default) when compared with those born in Chiapas (29.5% vs. 11.1%; P < 0.05). Unfavourable TB outcomes were also more prevalent among the TB patients with undernutrition, HIV or older age, but not DM (P < 0.05). Our study in Chiapas illustrates the challenges of other regions worldwide where social (e.g. indigenous origin, poverty, migration) and host factors (DM, undernutrition, HIV, older age) are associated with TB. Further understanding of these critical factors will guide local policy makers and health providers to improve TB management.

Primary motor cortex alterations in Alzheimer disease: A study in the 3xTg-AD model. / Alteraciones en la corteza motora primaria en la enfermedad de Alzheimer: estudio en el modelo 3xTg-AD.

INTRODUCTION: In humans and animal models, Alzheimer disease (AD) is characterised by accumulation of amyloid-ß peptide (Aß) and hyperphosphorylated tau protein, neuronal degeneration, and astrocytic gliosis, especially in vulnerable brain regions (hippocampus and cortex). These alterations are associated with cognitive impairment (loss of memory) and non-cognitive impairment (motor impairment). The purpose of this study was to identify cell changes (neurons and glial cells) and aggregation of Aß and hyperphosphorylated tau protein in the primary motor cortex (M1) in 3xTg-AD mouse models at an intermediate stage of AD. METHODS: We used female 3xTg-AD mice aged 11 months and compared them to non-transgenic mice of the same age. In both groups, we assessed motor performance (open field test) and neuronal damage in M1 using specific markers: BAM10 (extracellular Aß aggregates), tau 499 (hyperphosphorylated tau protein), GFAP (astrocytes), and Klüver-Barrera staining (neurons). RESULTS: Female 3xTg-AD mice in intermediate stages of the disease displayed motor and cellular alterations associated with Aß and hyperphosphorylated tau protein deposition in M1. CONCLUSIONS: Patients with AD display signs and symptoms of functional impairment from early stages. According to our results, M1 cell damage in intermediate-stage AD affects motor function, which is linked to progression of the disease.

[Seclusion and restraint: From prescription to decision]. / Isolement et contention : de la prescription à la décision.

Psychiatric care has always included patients in crisis who are potentially dangerous or agitated. Faced with the many issues they may encounter, the therapeutic relationship has always been prioritized over all other considerations. However, the practice of seclusion and restraint has been steadily increasing in the past few decades. Their use is becoming customary rather than exceptional and consequently fosters less thought by the care teams. In the Healthcare System Modernization Act of January 26th, 2016, the lawmakers sought to underline the freedom-destroying nature of these practices and the necessity of their regulation. This law represents a fundamental change in the nature of seclusion and restraint. What was but a simple prescription becomes a conscious decision of depriving someone of her or his freedom and must only be considered as a last resort. The changes in the Law and the recent changes in the recommendations for clinical practice by the French National Institute of Health invite reflection. Many questions remain about the origins of violence, the reasons for the increasing use of seclusion and restraint measures, and the alternatives that have been developed. Many theories suggest that the less stressful and constrained an environment is, the more empowered the patient will be. He is an actor in his own care and is considered a full active participant. The Law is reconciled with caregivers initiating a reflection on the benefits of these measures regarding the violation of fundamental freedoms. Reflection on psychiatric care and the quality of its management must be the focus when caring for patients in crisis.