Diagnosis and management of isthmocele (Cesarean scar defect): a SWOT analysis.

The purpose of this State-of-the-Art Review was to provide a strategic analysis, in terms of strengths, weaknesses, opportunities and threats (SWOT analysis), of the current evidence regarding the management of uterine isthmocele (Cesarean scar defect). Strengths include the fact that isthmocele can be diagnosed on two-dimensional transvaginal ultrasound, and that surgical repair may restore natural fertility potential and prevent secondary infertility, as well as reduce the risk of miscarriage and other obstetric complications. However, there is a lack of high-quality evidence regarding the best diagnostic method and criteria, as well as the potential benefits of surgical repair with respect to fertility. There is a need for experienced surgeons skilled in the various isthmocele repair techniques. Isthmocele repair does not prevent the need for Cesarean delivery in subsequent pregnancies. There is increasing awareness regarding the accuracy of transvaginal ultrasound in diagnosing isthmocele. This may lead to surgical correction and prevention of obstetric and perinatal complications in subsequent pregnancies, including Cesarean scar pregnancy. Regarding threats, the existence of different surgical techniques means that there is a risk of selecting an inadequate approach if the type of isthmocele and the patient's characteristics are not considered. There is a risk of overtreatment when asymptomatic defects are repaired surgically. Finally, there is an absence of cost-effectiveness analyses to justify routine repair. Thus, while there are many data suggesting that isthmocele has an adverse effect on both natural fertility and the outcome of assisted reproduction techniques, high-quality evidence to support surgical isthmocele repair in all asymptomatic patients desiring future fertility are lacking. There is increasing agreement to recommend hysteroscopic repair of isthmocele as a first-line approach as long as the residual myometrial thickness is at least 2.5-3.0 mm. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

[Surgical management of non-tuberculous mycobacterial lymphadenitis in a third level center]. / Manejo quirúrgico de la linfadenitis por micobacterias no tuberculosas en un centro de tercer nivel.

AIM OF STUDY: To describe our experience in the management of non-tuberculosis mycobacterial lymphadenitits (NTML). METHODS: Retrospective analysis of patients who underwent surgery for NTML in our centre during the period between 2010-2017. Demographic data, diagnostic tests, treatment and follow up information were recovered from medical records. RESULTS: 65 patients (26 male/39 female) with a mean age of 31 months (range 7 months-12 years) were intervened during the period of study. As diagnostic tests, chest X-ray was performed in 92.3% of patients with normal result in all cases, Mantoux test was positive in 20.3%, inconclusive in 12.5% and negative in 67.1%. Preoperative fine needle aspiration was positive for NTML (granulomatous necrotizing lymphadenitis) in 93.7% whereas culture for mycobacteria was only positive in 23.4% of cases, being Mycobacterium lentiflavum the most frequent agent found. Mean preoperative waiting time was 2.5 months with 7.7% of fistulization previous to surgery. Mean hospital stay was 1,1 days and there were no intraoperative complications. Mean follow up time was 5.5 months (range 1-24 months) during which 19 cases of temporal facial paralysis were noted, among which only 2 persisted after one year. CONCLUSIONS: NTML is a disease with a growing incidence in our country. It is important to make an early diagnosis and surgical treatment in order to avoid complications, as surgery has demonstrated to be safe and effective, with a low rate of complications. We believe the actual protocols should be revised/checked due to low effectiveness of diagnostic tests.

OBJETIVOS: Describir nuestra experiencia en el manejo de la linfadenitis por micobacterias no tuberculosas (LMNT). MATERIAL Y METODOS: Análisis retrospectivo de 65 pacientes (26 varones/ 39 mujeres) intervenidos en nuestro centro de LMNT durante los años 2010-2017. Se analizaron datos demográficos, pruebas complementarias realizadas y datos de seguimiento. RESULTADOS: La edad media fue de 31 meses (rango 7 meses-12 años). Para el diagnóstico la radiografía de tórax se realizó al 92,3% de pacientes, siendo en todos normal. El Mantoux fue positivo en 20,3%, dudoso en 12,5% y negativo en 67,1%. La PAAF preoperatoria fue diagnóstica (linfadenitis granulomatosa necrotizante) en 93,7% mientras que el cultivo para micobacterias fue positivo solo en 23,4%, siendo el Mycobacterium lentiflavum el patógeno más frecuentemente encontrado. El tiempo de espera preoperatorio fue de 2,5 meses con un porcentaje de fistulización previo a la cirugía de 7,7%. La estancia hospitalaria media fue 1,1 días y no hubo complicaciones perioperatorias. El tiempo medio de seguimiento fue 5,5 meses (rango 1-24 meses) observándose 19 casos de parálisis facial temporal, de los cuales 2 persistieron al cabo de 1 año. CONCLUSIONES: La LMNT es una enfermedad cada vez más frecuente en nuestro medio. Es importante realizar un diagnóstico y tratamiento precoz, puesto que el tratamiento quirúrgico ha demostrado ser seguro y eficaz asociando baja tasa de complicaciones. Creemos que los protocolos actuales se deben revisar, debido a la escasa rentabilidad de algunas pruebas complementarias.

Analysis of melanopsin gene expression in the rabbit retina at different ages.

Melanopsin is the photopigment of intrinsically photosensitive retinal ganglion cells that mediate non-visual responses to light. The aim of this study was to describe and analyze melanopsin gene expression in the rabbit retina at different ages and compare its expression with the prototypic gene of retinal ganglion cells (Thy-1 gene). Expression levels of OPN4, Thy-1, and GADPH genes were measured by real-time PCR at 3, 4, 8, 11, 12, 17, 19, 20, 23, 27, 32, and 47 postnatal days. We also regrouped the days before and after day 12 of life (pre-photic and post-photic stage, respectively). Average expression of the OPN4 gene between days was similar (P = 0.713), but was statistically different in the Thy-1 gene (P = 0.004). Also, no significant differences were found in OPN4 gene expression pre-photic and post-photic stage (P = 0.629); however, Thy-1 expression was higher in the pre-photic stage, almost double, than in the post-photic stage, with significant differences (P = 0.001). This is the first report describing OPN4 gene expression in the rabbit retina at different ages. We demonstrated that the OPN4 gene is constantly expressed at all early stages, even before the onset of photoentrainment by the pups and that Thy-1 and OPN4 gene expressions are out of phase.

[Surgery in times of crisis: conservative treatment of pectus carinatum by static corset]. / Cirugía en tiempos de crisis: tratamiento conservador del pectus carinatum mediante corsé estático.

INTRODUCTION: Dynamic compression system is the elective treatment for chondrogladiolar pectus carinatum. Nevertheless, its high cost poses a problem for its prescription in places where it is not subsidized. This article analyzes the experience of the Paediatric Plastic Surgery Service at a third grade hospital in the treatment of this deformity with a static compression system. MATERIALS AND METHODS: The study presents a descriptive, retrospective analysis of 30 patients with pectus carinatum treated with a static compression system. Furthermore, we describe the protocol of treatment used at our unit, and we analyse the satisfaction with bracing therapy, and its relation to therapeutic compliance. RESULTS: The study includes 28 boys and 2 girls. 93% of the patients presented a chondrogladiolar pectus carinatum. At the moment of finishing the study, 11 patients have completed the treatment, 14 still bracing, and 5 were lost in the follow-up. Satisfaction questionnaires were answered by 19 patients. CONCLUSION: Bracing therapy with static compression system is the treatment of choice for chondrogladiolar pectus carinatum in our unit, because of its effectiveness and lower price. Quality of life questionnaires show better marks in patients that are in the second phase of treatment.

INTRODUCCION: El corsé de compresión dinámica constituye el tratamiento de elección de las formas condrogladiolares de pectus carinatum. Sin embargo, su elevado coste supone un problema para su prescripción en las comunidades en las que no se encuentra subvencionado. El presente trabajo analiza la experiencia de la Unidad de Cirugía Plástica Infantil de un hospital terciario en el manejo de esta patología mediante tratamiento ortopédico con corsé de compresión estática. MATERIAL Y METODOS: Se realiza un estudio descriptivo, de carácter retrospectivo, de 30 pacientes afectos de pectus carinatum tratados mediante ortesis estática. Además, se expone el protocolo de actuación de la unidad, y se analiza la satisfacción de los pacientes con el tratamiento, y su relación con la adherencia terapéutica. RESULTADOS: La muestra incluye 28 varones y 2 mujeres. El 93% de los pacientes presentaban una malformación de tipo condrogladiolar. En el momento de finalización del estudio, 11 pacientes habían completado la terapia, 14 continuaban en tratamiento, y 5 fueron pérdidas en el seguimiento. Las encuestas de satisfacción pudieron ser realizadas a 19 pacientes. CONCLUSION: La terapia con corsé de compresión estática resulta eficaz, con un coste asociado más bajo al de la terapia dinámica, convirtiéndose en el tratamiento de referencia de nuestra unidad. Los cuestionarios de calidad de vida empleados muestran mejores puntuaciones en pacientes en fase de mantenimiento, respecto a pacientes en fase de corrección.

[Initial results of robotic esophagectomy for esophageal cancer]. / Resultados iniciales de la esofaguectomía robótica en el cáncer de esófago.

INTRODUCTION: There is scant experience with robot-assisted esophagectomy in cases of esophageal and gastro-esophageal junction cancer. Our aim is to report our current experience. PATIENTS AND METHODS: Observational cohort study of the first 32 patients who underwent minimally invasive esophagectomy for esophageal cancer from September 2011 to June 2014. The gastric tube was created laparoscopically. In the thoracic field, a robot-assisted thoracoscopic approach was performed in the prone position with intrathoracic robotic hand-sewn anastomosis. Patient and tumour characteristics, surgical technique, short-term outcomes (morbidity and mortality) and oncological results (radicality and number of removed nodes) were evaluated. RESULTS: Thirty-two patients, with a mean age of 58 years (34-74) were treated by a totally minimally invasive esophagectomy: robotic laparoscopy and thoracoscopy (11 McKeown and 21 Ivor-Lewis). Twenty-nine received neoadjuvant chemoradiotherapy. There were no conversions to open surgery. Console time was 218minutes (190-285). Blood loss was 170ml (40-255). One patient died from cardiac disease. Nine patients had a major complication (Dindo-Clavien grade II or higher). There was no case of respiratory complication or recurrent laryngeal nerve palsy. Five patients had intrathoracic fistula, 4 radiological and one clinical. Three had chylothorax, 2 cervical fistula and one gastric tube necrosis. The median hospital stay was 12 days (8-50). All the resections were R0 and the median of removed lymph nodes was 16 (2-23). CONCLUSIONS: Our results suggest that minimally invasive esophagectomy with robot-assisted thoracoscopy is safe and achieves oncological standards.

Indication, performance and outcomes of adrenal vein sampling in patients with primary hyperaldosteronism.

Primary hyperaldosteronism (PAH) is an important cause of secondary hypertension (HTN). The study of the same requires a high clinical suspicion in addition to a hormonal study that confirms hormonal hypersecretion. It is important to start the appropriate treatment once the diagnosis is confirmed, and for this is necessary to demonstrate whether the hormonal hypersecretion is unilateral (patients who could be candidates for surgical treatment) or bilateral (patients who are candidates for pharmacological treatment only). At the Hospital del Mar since 2016 there has been a multidisciplinary work team in which Nephrologists, Endocrinologists, Radiologists and Surgeons participate to evaluate cases with suspected hyperaldosteronism and agree on the best diagnostic-therapeutic approach for these patients, including the need for adrenal vein sampling, which is a technique that in recent years has become the gold standard for the study of PAH. In the present study we collect the experience of our centre in performing AVC and its usefulness for the management of these patients.

Clinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease.

INTRODUCTION: Charcot-Marie-Tooth disease (CMT) is classified according to neurophysiological and histological findings, the inheritance pattern, and the underlying genetic defect. The objective of these guidelines is to offer recommendations for the diagnosis, prognosis, follow-up, and treatment of this disease in Spain. MATERIAL AND METHODS: These consensus guidelines were developed through collaboration by a multidisciplinary panel encompassing a broad group of experts on the subject, including neurologists, paediatric neurologists, geneticists, physiatrists, and orthopaedic surgeons. RECOMMENDATIONS: The diagnosis of CMT is clinical, with patients usually presenting a common or classical phenotype. Clinical assessment should be followed by an appropriate neurophysiological study; specific recommendations are established for the parameters that should be included. Genetic diagnosis should be approached sequentially; once PMP22 duplication has been ruled out, if appropriate, a next-generation sequencing study should be considered, taking into account the limitations of the available techniques. To date, no pharmacological disease-modifying treatment is available, but symptomatic management, guided by a multidiciplinary team, is important, as is proper rehabilitation and orthopaedic management. The latter should be initiated early to identify and improve the patient's functional deficits, and should include individualised exercise guidelines, orthotic adaptation, and assessment of conservative surgeries such as tendon transfer. The follow-up of patients with CMT is exclusively clinical, and ancillary testing is not necessary in routine clinical practice.

Oleate prevents saturated-fatty-acid-induced ER stress, inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism.

AIMS/HYPOTHESIS: Although the substitution of saturated fatty acids with oleate has been recommended in the management of type 2 diabetes mellitus, the mechanisms by which oleate improves insulin resistance in skeletal muscle cells are not completely known. Here, we examined whether oleate, through activation of AMP-activated protein kinase (AMPK), prevented palmitate-induced endoplasmic reticulum (ER) stress, which is involved in the link between lipid-induced inflammation and insulin resistance. METHODS: Studies were conducted in mouse C2C12 myotubes and in the human myogenic cell line LHCN-M2. To analyse the involvement of AMPK, activators and inhibitors of this kinase and overexpression of a dominant negative AMPK construct (K45R) were used. RESULTS: Palmitate increased the levels of ER stress markers, whereas oleate did not. In palmitate-exposed cells incubated with a lower concentration of oleate, the effects of palmitate were prevented. The induction of ER stress markers by palmitate was prevented by the presence of the AMPK activators AICAR and A-769662. Moreover, the ability of oleate to prevent palmitate-induced ER stress and inflammation (nuclear factor-kappa B [NF-κB] DNA-binding activity and expression and secretion of IL6) as well as insulin-stimulated Akt phosphorylation and 2-deoxyglucose uptake was reversed in the presence of the AMPK inhibitor compound C or by overexpression of a dominant negative AMPK construct. Finally, palmitate reduced phospho-AMPK levels, whereas this was not observed in oleate-exposed cells or in palmitate-exposed cells supplemented with oleate. CONCLUSIONS/INTERPRETATION: Overall, these findings indicate that oleate prevents ER stress, inflammation and insulin resistance in palmitate-exposed skeletal muscle cells by activating AMPK.

Role of A1c in the postpartum screening of women with gestational diabetes.

OBJECTIVE: This study aimed to determine whether A1c detects a different prediabetes prevalence in women with a history of gestational diabetes mellitus (GDM) compared to those diagnosed with oral glucose tolerance test (OGTT) and the influence of haemoglobin concentrations on A1c levels. DESIGN AND PATIENTS: We evaluated carbohydrate metabolism status by performing OGTT and A1c tests in 141 postpartum women with prior GDM in the first year post-delivery. RESULTS: The overall prevalence of prediabetes was 41.8%. Prevalence of isolated A1c 5.7-6.4%, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) was 10.6%, 7.1%, and 9.2%, respectively. Isolated A1c 5.7-6.4% was associated with Caucasian origin (66.7% versus 32.6%, p = 0.02) and with higher LDL cholesterol concentrations (123 ± 28.4 mg/dl versus 101.6 ± 19.2 mg/dl, p = 0.037) compared with patients diagnosed by OGTT (IFG or IGT). Women with postpartum anaemia had similar A1c levels to those with normal haemoglobin concentrations (5.5% ± 0.6% versus 5.4% ± 0.4%, p = 0.237). CONCLUSIONS: Use of A1c in postpartum screening of women with GDM detected an additional 10.6% of patients with prediabetes and a more adverse lipid profile. Haemoglobin concentrations did not influence A1c values.

The peroxisome proliferator-activated receptor (PPAR) ß/δ agonist GW501516 inhibits IL-6-induced signal transducer and activator of transcription 3 (STAT3) activation and insulin resistance in human liver cells.

AIM/HYPOTHESIS: IL-6 induces insulin resistance by activating signal transducer and activator of transcription 3 (STAT3) and upregulating the transcription of its target gene SOCS3. Here we examined whether the peroxisome proliferator-activated receptor (PPAR)ß/δ agonist GW501516 prevented activation of the IL-6-STAT3-suppressor of cytokine signalling 3 (SOCS3) pathway and insulin resistance in human hepatic HepG2 cells. METHODS: Studies were conducted with human HepG2 cells and livers from mice null for Pparß/δ (also known as Ppard) and wild-type mice. RESULTS: GW501516 prevented IL-6-dependent reduction in insulin-stimulated v-akt murine thymoma viral oncogene homologue 1 (AKT) phosphorylation and in IRS-1 and IRS-2 protein levels. In addition, treatment with this drug abolished IL-6-induced STAT3 phosphorylation of Tyr7°5 and Ser7²7 and prevented the increase in SOCS3 caused by this cytokine. Moreover, GW501516 prevented IL-6-dependent induction of extracellular-related kinase 1/2 (ERK1/2), a serine-threonine protein kinase involved in serine STAT3 phosphorylation; the livers of Pparß/δ-null mice showed increased Tyr7°5- and Ser7²7-STAT3 as well as phospho-ERK1/2 levels. Furthermore, drug treatment prevented the IL-6-dependent reduction in phosphorylated AMP-activated protein kinase (AMPK), a kinase reported to inhibit STAT3 phosphorylation on Tyr7°5. In agreement with the recovery in phospho-AMPK levels observed following GW501516 treatment, this drug increased the AMP/ATP ratio and decreased the ATP/ADP ratio. CONCLUSIONS/INTERPRETATION: Overall, our findings show that the PPARß/δ activator GW501516 prevents IL-6-induced STAT3 activation by inhibiting ERK1/2 phosphorylation and preventing the reduction in phospho-AMPK levels. These effects of GW501516 may contribute to the prevention of cytokine-induced insulin resistance in hepatic cells.

Long-term results of biopsy-guided selection and allocation of kidneys from older donors in older recipients.

In our old-for-old program, we discard or allocate older extended criteria donor kidneys to single (SKT) or dual kidney transplantation (DKT) depending on histological Remuzzi's score in recipients older than 60 years. Here, we analyze the long-term results of this program and try to identify independent predictors of patient and graft survival. Between December 1996 and January 2008, we performed 115 SKT and 88 DKT. Discard rate was 15%. Acute rejection incidence was higher in SKT than in DKT (22.6% vs. 11.4%, p = 0.04). Renal function was better in DKT than in SKT up to 5 years after transplantation. Surgical complications were frequent in DKT. Ten-year cumulative graft survival was significantly lower in the SKT group (31% vs. 53%, p = 0.03). In SKT, histological score 4 provided similar graft survival than 3 or less, whereas in DKT score 4, 5 or 6 displayed similar outcome. Finally, independent predictors of graft survival were history of major adverse cardiac event and 1-year serum creatinine, rather than SKT or DKT. In conclusion, this biopsy-guided old-for-old strategy resulted in acceptable long-term graft survival. Our results suggest that DKT should be considered for scores of 5 or 6 only.

Free fatty acids and the metabolic syndrome in patients with obstructive sleep apnoea.

Obesity and metabolic syndrome (MS) occur frequently in patients with obstructive sleep apnoea syndrome (OSAS). We hypothesised that circulating free fatty acids (FFAs) are elevated in OSAS patients independently of obesity. This elevation may contribute to the development of MS in these patients. We studied 119 OSAS patients and 119 controls. Participants were recruited and studied at sleep unit of our institution (Hospital Universitari Son Dureta, Palma de Mallorca, Spain) and were matched for sex, age and body mass index (BMI). The occurrence of MS was analysed by clinical criteria. Serum levels of FFAs, glucose, triglycerides, cholesterol, high-density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, C-reactive protein and 8-isoprostanes were determined. Prevalence of MS was higher in OSAS than in the control group (38 versus 21%; p=0.006). OSAS patients had higher FFAs levels than controls (mean±sd 12.2±4.9 versus 10.5±5.0 mg·dL(-1); p=0.015). Among subjects without MS, OSAS patients (OSAS+ MS-) showed higher levels of FFAs than controls (OSAS- MS-) (11.6±4.7 versus 10.0±4.4 mg·dL(-1); p=0.04). In a multiple regression model, after adjustment for age, sex, BMI and the presence of MS, FFAs were significantly associated with apnoea/hypopnoea index (p=0.04). This study shows that FFAs are elevated in OSAS and could be one of the mechanisms involved in the metabolic complications of OSAS.

Analysis of the diagnostic pathway and delay in patients with amyotrophic lateral sclerosis in the Valencian Community.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an insidious, clinically heterogeneous neurodegenerative disease associated with a diagnostic delay of approximately 12 months. No study conducted to date has analysed the diagnostic pathway in Spain. METHODS: We gathered data on variables related to the diagnostic pathway and delay for patients diagnosed with ALS between October 2013 and July 2017. RESULTS: The study included 143 patients with ALS (57% men; 68% spinal onset). Patients were diagnosed in public centres in 86% of cases and in private centres in 14%. The mean diagnostic delay was 13.1 months (median 11.7). Patients were examined by neurologists a mean time of 7.9 months after symptom onset, with diagnosis being made 5.2 months later. Half of all patients underwent unnecessary diagnostic tests and multiple electrophysiological studies before diagnosis was established. Diagnostic delay was longer in cases of spinal onset (P=.008) due to onset of the disease in the lower limbs. No differences were found between the public and private healthcare systems (P=.897). CONCLUSIONS: The diagnostic delay in ALS in Spain is similar to that of neighbouring countries and seems to depend on disease-related factors, not on the healthcare system. Patients with lower-limb onset ALS constitute the greatest diagnostic challenge. Misdiagnosis is frequent, and partly attributable to an incorrect approach or erroneous interpretation of electrophysiological studies. Specific training programmes for neurologists and general neurophysiologists and early referral to reference centres may help to reduce diagnostic delay.

Point-of-care lung ultrasound predicts in-hospital mortality in acute heart failure.

BACKGROUND: B-lines have been associated with adverse clinical outcomes in patients with heart failure (HF) when found at hospital discharge or during outpatient visits. Whether lung ultrasound (LUS) assessed B-lines may predict in-hospital mortality in patients with acute HF is still undetermined. AIM: To evaluate the association between B-lines on admission and in-hospital mortality among patients admitted with acute HF. METHODS: Hand-held LUS was used to examine patients with acute HF. LUS was performed in eight chest zones with a pocket ultrasound device and analyzed offline. The association between B-lines and in-hospital mortality was assessed using Cox regression models. RESULTS: We included 62 patients with median age 56 years, 69.4% men, and median left ventricle ejection fraction 25%. The sum of B-lines ranged from 0 to 53 (median 6.5). An optimal receiver operating characteristic-determined cut-off of ≥19 B-lines demonstrated a sensitivity of 57% and a specificity of 86% (area under the curve 0.788) for in-hospital mortality. The incremental prognostic value of LUS when compared with lung crackles or peripheral edema by integrated discrimination improvement was 12.96% (95% CI: 7.0-18.8, P = 0.02). Patients with ≥19 B-lines had a 4-fold higher risk of in-hospital mortality (HR 4.38; 95% CI: 1.37-13.95, P < 0.01). CONCLUSION: In patients admitted with acute HF, point-of-care LUS measurements of pulmonary congestion (B-lines) are associated with in-hospital mortality.

The Mars Environmental Dynamics Analyzer, MEDA. A Suite of Environmental Sensors for the Mars 2020 Mission.

NASA's Mars 2020 (M2020) rover mission includes a suite of sensors to monitor current environmental conditions near the surface of Mars and to constrain bulk aerosol properties from changes in atmospheric radiation at the surface. The Mars Environmental Dynamics Analyzer (MEDA) consists of a set of meteorological sensors including wind sensor, a barometer, a relative humidity sensor, a set of 5 thermocouples to measure atmospheric temperature at ∼1.5 m and ∼0.5 m above the surface, a set of thermopiles to characterize the thermal IR brightness temperatures of the surface and the lower atmosphere. MEDA adds a radiation and dust sensor to monitor the optical atmospheric properties that can be used to infer bulk aerosol physical properties such as particle size distribution, non-sphericity, and concentration. The MEDA package and its scientific purpose are described in this document as well as how it responded to the calibration tests and how it helps prepare for the human exploration of Mars. A comparison is also presented to previous environmental monitoring payloads landed on Mars on the Viking, Pathfinder, Phoenix, MSL, and InSight spacecraft.

Activation of the EGFR/ERK pathway in high-grade mucoepidermoid carcinomas of the salivary glands.

BACKGROUND: Mucoepidermoid carcinoma (MEC) shows differences in biological behaviour depending mainly on its histological grade. High-grade tumours usually have an aggressive biological course and they require additional oncological treatment after surgery. METHODS: In a series of 43 MECs of the salivary glands, we studied the epidermal growth factor receptor (EGFR) gene by using dual-colour chromogenic in situ hybridisation (CISH). Moreover, we assessed the protein expressions of the EGFR and the activated extracellular signal-regulated kinases (pERK1/2) by using immunohistochemistry. These results were correlated with the histological grade of the tumours and the outcome of the patients. RESULTS: The CISH study demonstrated a high-EGFR gene copy number, with balanced chromosome 7 polysomy, in 8 out of 11 high-grade MECs (72.7%), whereas 27 low-grade and 15 intermediate-grade tumours had a normal EGFR gene copy number (P<0.001). The EGFR gene gains correlated with disease-free interval (P=0.003) and overall survival of the patients (P=0.019). The EGFR protein expression had a significant correlation with the histological grade of the tumours but not with the outcome of the patients. The pERK1/2 expression correlated with histological grade of tumours (P<0.001), disease-free interval (P=0.004) and overall survival (P=0.001). CONCLUSIONS: The EGFR/ERK pathway is activated in high-grade MECs with aggressive behaviour. Patients with these tumours who require oncological treatment in addition to surgery could benefit from EGFR and mitogen-activated protein kinase pathway inhibitors.

Disodium ascorbyl phytostanol phosphate (FM-VP4), a modified phytostanol, is a highly active hypocholesterolaemic agent that affects the enterohepatic circulation of both cholesterol and bile acids in mice.

Disodium ascorbyl phytostanol phosphate (FM-VP4) is a synthetic compound derived from sitostanol and campestanol that has proved to be efficient as a cholesterol-lowering therapy in mice and human subjects. However, the mechanism of action of FM-VP4 remains unknown. The present study tests the ability of FM-VP4 to alter intestinal and liver cholesterol homeostasis in mice. Female C57BL/6J mice were fed either a control chow or a 2 % FM-VP4-enriched diet for 4 weeks. FM-VP4 reduced the in vivo net intestinal cholesterol absorption and plasma and liver cholesterol concentrations by 2.2-, 1.5- and 1.6-fold, respectively, compared with control mice. Furthermore, FM-VP4 also showed an impact on bile acid homeostasis. In FM-VP4 mice, liver and intestinal bile acid content was increased by 1.3- and 2.3-fold, respectively, whereas faecal bile acid output was 3.3-fold lower. FM-VP4 also increased the intestinal absorption of orally administered [3H]taurocholic acid to small intestine in vivo. Inhibition of intestinal cholesterol absorption by FM-VP4 was not mediated via transcriptional increases in intestine liver X receptor (LXR)-alpha, adenosine triphosphate-binding cassette transporter (ABC)-A1, ABCG5/G8 nor to decreases in intestinal Niemann-Pick C1-like 1 (NPC1L1) expression. In contrast, FM-VP4 up-regulated liver LXRalpha, ABCA1, ABCG5, scavenger receptor class BI (SR-BI) and hydroxymethylglutaryl coenzyme A reductase (HMGCoA-R) gene expression, whereas it down-regulated several farnesoid X receptor (FXR)-target genes such as cytochrome P450 family 7 subfamily A polypeptide 1 (CYP7A1) and Na+/taurocholate co-transporter polypeptide (NTCP). In conclusion, FM-VP4 reduced intestinal cholesterol absorption, plasma and liver cholesterol and affected bile acid homeostasis by inducing bile acid intestinal reabsorption and changed the liver expression of genes that play an essential role in cholesterol homeostasis. This is the first phytosterol or stanol that affects bile acid metabolism and lowers plasma cholesterol levels in normocholesterolaemic mice.

Strong opioids and non-cancer chronic pain in Catalonia. An analysis of the family physicians prescription patterns. / Opioides fuertes y dolor crónico no oncológico en Cataluña. Análisis del patrón de prescripción por parte de los médicos de familia.

OBJECTIVE: To identify family doctor prescription patterns for strong opioids for chronic, non-cancer-related pain. MATERIALS AND METHODS: Design A descriptive study based on a self-administered email questionnaire. LOCATION: All primary health care centres in Catalonia. PARTICIPANTS: 3,602 family doctors, all members of the Catalan Society of Family and Community Medicine. INTERVENTIONS: Email survey of Catalan family doctors. MAIN MEASUREMENTS: Demographic data, number of patients treated with potent opioids for chronic non-cancer pain, type of opioid used and indications, prescribing patterns and relationship with the Pain Management Unit. RESULTS: A total of 551 answers were obtained from 3,602 questionnaires sent (response rate of 15.3%), in which 480 physicians (87%) prescribed strong opioids for musculoskeletal pain, 268 (48.6%) prescribed ultra-rapid fentanyl and 434 (78.7%) reduced benzodiazepines dosage when prescribing potent opioids. The most common adverse effects were constipation and nausea. The main problems related with opioid prescription were improper use (341, 71%) and patient and/or practitioner reluctance (87, 18.1%). The assessment of the relationship with Pain Management Units was 2±1 (on a 1 to 5 scale), with communication (271, 52.2%) and accessibility (141, 27.1%) being the areas most in need of improvement. CONCLUSIONS: Opioid prescribing patterns generally follow clinical guidelines (e.g. reduction of benzodiazepine use or dose titration). However, there are some areas of improvement, such as sparse use of laxatives or use of ultra-rapid opioids for unapproved indications and in patients with no background opioid therapy. Family doctors perceive patient reluctance to adhere to the prescribed treatment, and call for specific training and better relationships with Pain Management Units.

Oral rapamycin: an alternative in children with complicated vascular abnormalities. / Rapamicina oral: una alternativa en niños con anomalías vasculares complicadas.

OBJECTIVE: Sirolimus mTOR inhibitor represents a major advance in the treatment of patients with complicated vascular abnormalities. The objective of this study was to present our series of pediatric patients with vascular abnormalities treated with oral sirolimus, and to conduct a review of the relevant literature. MATERIAL AND METHODS: A retrospective analysis of patients with complicated vascular abnormalities treated with oral sirolimus in our healthcare facility from 2016 was carried out. Initial dosage was 0.8 mg/m2 every 12 hours, and therapeutic range was 5-15 ng/ml. All patients received trimethoprim-sulfamethoxazole prophylaxis. RESULTS: 6 children -3 boys and 3 girls- with a mean age of 9.5 years at treatment initiation were included. 3 of them had head and neck lymphatic malformation, 2 had lower limb venous malformation, and 1 had combined lymphatic-venous malformation at the thoracoabdominal level. They all had received multiple previous treatments without improvement. Following sirolimus initiation, 5 patients had clinical improvement (mean time: 3.6 months) and 4 had radiological improvement (mean time: 6.6 months). Mild and transitory adverse effects were noted in the 3 cases. Today, 5 patients remain under treatment. CONCLUSIONS: Oral sirolimus is an effective and safe treatment in patients with complicated vascular abnormalities. Our results support sirolimus use in lymphatic and venous malformations in which previous treatments have failed, with a good symptomatic and, to a lesser extent, radiological response.

OBJETIVOS: El uso del inhibidor mTOR sirolimus ha supuesto un avance en el tratamiento de pacientes con anomalías vasculares complicadas. El objetivo de este estudio es presentar nuestra serie de pacientes pediátricos con anomalías vasculares tratados con sirolimus oral y hacer una revisión de la literatura al respecto. MATERIAL Y METODOS: Se realizó un análisis retrospectivo de los pacientes con anomalías vasculares complicadas tratados con sirolimus oral en nuestro centro desde el año 2016. La dosis inicial utilizada fue de 0,8 mg/m2 cada 12 horas y el rango terapéutico de 5-15 ng/ml. Todos los pacientes recibieron profilaxis con trimetoprim-sulfametoxazol. RESULTADOS: Se incluyeron seis niños, tres varones y tres mujeres, con una edad media al inicio del tratamiento de 9,5 años. Tres presentaban una malformación linfática en cabeza y cuello, dos una malformación venosa en miembro inferior y la última una malformación combinada linfática-venosa a nivel toracoabdominal. Todos habían recibido múltiples tratamientos previos sin mejoría. Tras el inicio de sirolimus, cinco pacientes mejoraron clínicamente (tiempo medio 3,6 meses) y cuatro radiológicamente (tiempo medio 6,6 meses). Se registraron efectos adversos leves y transitorios en tres casos. Actualmente, cinco pacientes continúan con el tratamiento. CONCLUSIONES: El sirolimus oral es un tratamiento eficaz y seguro en pacientes con anomalías vasculares complicadas. Nuestros resultados apoyan su uso en malformaciones linfáticas y venosas en las que han fracasado otros tratamientos, presentando buenas respuestas sintomáticas y, en menor medida, radiológicas.