Impact of Pleural Lavage Cytology Positivity on Early Recurrence After Surgery for Non-Small Cell Lung Cancer.

OBJECTIVE: The aim of this study was to elucidate the impact of pleural lavage cytology positivity on early recurrence in patients operated on non-small cell lung cancer (NSCLC). METHODS: This is a multicentre prospective cohort study of 684 patients undergoing an anatomical lung resection for NSCLC between October 2015 and October 2017 at 12 national centres. A pleural lavage was performed before and after lung resection. The association between the different predictors of early recurrence and PLC positivity was performed using univariate and multivariate logistic regression models. A propensity score analysis was performed by inverse probability weighting (IPSW) using average treatment effect (ATE) estimation to analyse the impact of PLC positivity on early recurrence. RESULTS: Overall PLC positivity was observed in 15 patients (2.2%). After two years, 193 patients (28.2%) relapsed, 182 (27.2%) with a negative PLC and 11 (73.3%) with a positive PLC (p<0.001). Factors associated to early recurrence were adenocarcinoma histology (OR=1.59, 95%CI 1.06-2.38, p=0.025), visceral pleural invasion (OR=1.59, 95%CI 1.04-2.4, p=0.03), lymph node involvement (OR=1.84, 95%CI 1.14-2.96, p=0.013), advanced pathological stage (OR=2.12, 95%CI 1.27-3.54, p=0.004) and PLC positivity (OR=4.14, 95%CI 1.25-16.36, p=0.028). After IPSW, PLC positivity was associated with an increased risk of early recurrence (OR=3.46, 95%CI 2.25-5.36, p<0.001). CONCLUSIONS: Positive pleural lavage cytology was found to be the strongest predictor of early recurrence.

Effect of Adherend Thickness on Near-Field Ultrasonic Welding of Single-Lap CF/LMPAEK Thermoplastic Composite Joints.

Ultrasonic welding is a fast and promising joining technique for thermoplastic composite parts. Understanding how changing the part thickness affects the process is crucial to its future upscaling and industrialization. This article presents an initial insight into the effect of the adherend's thickness on the near-field ultrasonic welding of CF/LMPAEK thermoplastic composites. Different thicknesses of the top and bottom adherend were welded and analyzed using the output data of the welding equipment, temperature measurements, and other visual characterization techniques. Increasing the thickness of both the top and the bottom adherends showed to increase the power consumed during welding. An overshoot in the power needed at the onset of the welding process for increased thickness of the top adherend precluded welding beyond a threshold thickness of 4.72 mm. In the case of the thicker top adherends, there was also melting of the energy director and early fiber squeeze-out within the top adherend as a result of increased bulk heating. Increased bulk heating was hypothesized to be caused by increased hammering, as indicated by the amplitude readings for thicker adherends. Welding with a higher force, which is known to reduce hammering, corroborated this hypothesis as fiber squeeze-out within the top adherend was not observed. It is believed that hammering contributes to heating by causing an oscillatory impact excitation that is close to the natural frequencies of the system, which would result in amplification of the cyclic strain and subsequent increase in the viscoelastic heating in the adherend.

Estudio del ganglio centinela en el cáncer de mama por el método OSNA (One-Step Nucleic Acid Amplification) tras neoadyuvancia en el Hospital Universitario de Navarra / Sentinel lymph node study in breast cancer using the OSNA (one-step nucleic acid amplification) method after neoadjuvant treatment at Hospital Universitario de Navarra

Introducción: la biopsia selectiva de ganglio centinela (GC) es la técnica estándar para la estadificación axilar en el cáncer de mama. No hay consenso en el empleo del método OSNA (One-Step Nucleic Acid Amplification) para el análisis del GC en las pacientes que recibieron el tratamiento neoadyuvante (TNA). En este trabajo analizamos los resultados obtenidos con OSNA en estas pacientes para justificar su implantación en nuestro centro. Material y métodos: se seleccionaron 42 casos del grupo de 163 pacientes con CM tratadas con TNA en nuestro centro, a las que se realizó OSNA del GC, obteniéndose una media de 2,1 ganglios por paciente. Se analizó además la expresión de citoqueratina 19 (CK19), grado tumoral, fenotipo molecular y el grado de respuesta al TNA de estas pacientes. Se estudiaron los GC mediante técnica OSNA y los no centinelas por el método tradicional. Resultados: el grado tumoral fue 2-3 en el 97,6% de los casos, el fenotipo luminal A (17%), luminal B (38%), triple-negativo (26,1%) y HER2 (19%). La respuesta al TNA fue completa en el 59,5% de las pacientes y la expresión de CK19 no se vio modificada. Los ganglios estudiados fueron positivos en 9 pacientes (21,4%) en las que posteriormente se realizó una linfadenectomía y un único caso presentó ganglio no centinela afecto (2,3%). Conclusiones: el método OSNA para el estudio del GC tras el TNA es muy superior al método tradicional, ya que permite la detección intraoperatoria de grupo celular aislado y micrometástasis no detectables con los métodos tradicionales, evitando segundas intervenciones y falsos negativos al analizarse completo el GC, y demuestra que no se altera la expresión de CK19 con el TNA. (AU)

Background: Selective sentinel node (SN) biopsy is the standard technique for axillary staging in breast cancer (BC). There is no consensus on the use of OSNA (One-Step Acid Nucleic Amplification) method for SN in patients undergoing neoadjuvant treatment (NAT). We have studied the results obtained in our centre to justify the advantages of its implementation. Material and methods: 42 cases were selected from the group of 163 patients with BC treated with NAT, who underwent OSNA of the SN, obtaining a mean of 2.1 nodes per patient. We also analyzed cytokeratin 19 (CK19) expression, tumour grade, molecular phenotype and the degree of response to NAT in these patients. The SN were studied using the OSNA technique and non-sentinel nodes using the traditional method. Results: Tumour grade was 2-3 in 97.6% of cases, phenotype luminal A (17%), luminal B (38%), triple-negative (26.1%) and HER2 (19%). The response to NAT was complete in 59.5% of patients and CK19 expression was unchanged. The nodes studied were positive in 9 patients (21.4%) in whom lymphadenectomy was performed and only one case had a non-sentinel node involvement (2.3%). Conclusions: The OSNA method for the study of SN after NAT is far superior to the traditional method as it: It allows intraoperative detection of isolated cell group and micrometastases not detectable with traditional methods, avoiding second interventions. It avoids false negatives when the whole SN is analyzed. It shows that CK19 expression is not altered by NAT. (AU)

A Study on Through-the-Thickness Heating in Continuous Ultrasonic Welding of Thermoplastic Composites.

Continuous ultrasonic welding is a promising technique for joining thermoplastic composites structures together. The aim of this study was to gain further insight into what causes higher through-the-thickness heating in continuous ultrasonic welding of thermoplastic composites as compared to the static process. Thermocouples were used to measure temperature evolutions at the welding interface and within the adherends. To understand the mechanisms causing the observed temperature behaviours, the results were compared to temperature measurements from an equivalent static welding process and to the predictions from a simplified heat transfer model. Despite the significantly higher temperatures measured at the welding interface for the continuous process, viscoelastic bulk heat generation and not thermal conduction from the interface was identified as the main cause of higher through-the-thickness heating in the top adherend. Interestingly the top adherend seemed to absorb most of the vibrational energy in the continuous process as opposed to a more balanced energy share between the top and bottom adherend in the static process. Finally, the higher temperatures at the welding interface in continuous ultrasonic welding were attributed to pre-heating of the energy director due to the vibrations being transmitted downstream of the sonotrode, to reduced squeeze-flow of energy director due to the larger adherend size, and to heat flux originating downstream as the welding process continues.

The dangers of single-lap shear testing in understanding polymer composite welded joints.

Single-lap shear (SLS) joints are straightforward to manufacture. This makes them especially attractive for testing polymer composite welded joints. Owing to local heating, which is characteristic of composite welding processes, the production of more geometrically intricate joints (such as double-lap or scarfed joints) or bigger joints (such as end-notched flexure or double cantilever beam) typically entails significant complexity in the design of the welding process. Testing of SLS joints is also uncomplicated and, even though, owing to mixed-mode loading and uneven stress distribution, it does not provide design values, it is widely acknowledged as a valuable tool for comparison. Even so, comparing different aspects of composite welded joints through their corresponding SLS strength values alone can be deceptive. This paper shows that comparison of different welding processes, adherend materials, process parameters or different types of joining techniques through SLS testing is only meaningful when strength values are combined with knowledge on other aspects of the joints such as joint mesostructure, failure modes and joint mechanics. This article is part of a discussion meeting issue 'A cracking approach to inventing new tough materials: fracture stranger than friction'.

Mixed pathologies in pancreatic ß cells from subjects with neurodegenerative diseases and their interaction with prion protein.

Protein misfolding diseases refer to a variety of disorders that develop as a consequence of the misfolding of proteins in various organs. The etiologies of Parkinson's and Alzheimer's disease remain unclear, but it seems that type two diabetes and other prediabetic states could contribute to the appearance of the sporadic forms of these diseases. In addition to amylin deposition, other amyloidogenic proteins implicated in the pathophysiology of neurodegenerative diseases could have important roles in the pathogenesis of this disease. As we have previously demonstrated the presence of α-synuclein deposits in the pancreas of patients with synucleinopathies, as well as tau and Aß deposits in the pancreatic tissue of Alzheimer's disease patients, we studied the immunoreactivity of amylin, tau and α-synuclein in the pancreas of 138 subjects with neurodegenerative diseases or type two diabetes and assessed whether the pancreatic ß-cells of these subjects present cooccurrence of misfolded proteins. Furthermore, we also assessed the pancreatic expression of prion protein (PrP) in these subjects and its interaction, both in the pancreas and brain, with α-synuclein, tau, Aß and amylin. Our study shows, for the first time, that along with amylin, pancreatic α-synuclein, Aß, PrP and tau may contribute together to the complex pathophysiology of type two diabetes and in the appearance of insulin resistance in Alzheimer's and Parkinson's disease. Furthermore, we show that the same mixed pathologies that are observed in the brains of patients with neurodegenerative diseases are also present outside the nervous system. Finally, we provide the first histological evidence of an interaction between PrP and Aß, α-synuclein, amylin or tau in the pancreas and locus coeruleus. These findings will shed more light on the common pathological pathways shared by neurodegenerative diseases and type two diabetes, benefiting the exploration of common therapeutic strategies to prevent or treat these devastating amyloid diseases.

Severe intrahepatic cholestasis as the initial manifestation of light chain amyloidosis / Colestasis intrahepática grave como manifestación inicial de la amiloidosis por depósito de cadenas ligeras

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Carcinoma pleomorfo pulmonar con presentación como masa subsólida por extensa hemorragia peritumoral: a propósito de 2 casos / Two Cases of Pleomorphic Carcinoma of the Lung Presenting as a Subsolid Mass due to Extensive Peritumoral Hemorrhage

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Amylin as a potential link between type 2 diabetes and alzheimer disease.

OBJECTIVE: Alzheimer disease (AD) is the leading cause of dementia, and although its etiology remains unclear, it seems that type 2 diabetes mellitus (T2DM) and other prediabetic states of insulin resistance could contribute to the appearance of sporadic AD. As such, we have assessed whether tau and ß-amyloid (Aß) deposits might be present in pancreatic tissue of subjects with AD, and whether amylin, an amyloidogenic protein deposited in the pancreas of T2DM patients, might accumulate in the brain of AD patients. METHODS: We studied pancreatic and brain tissue from 48 individuals with no neuropathological alterations and from 87 subjects diagnosed with AD. We examined Aß and tau accumulation in the pancreas as well as that of amylin in the brain. Moreover, we performed proximity ligation assays to ascertain whether tau and/or Aß interact with amylin in either the pancreas or brain of these subjects. RESULTS: Cytoplasmic tau and Aß protein deposits were detected in pancreatic ß cells of subjects with AD as well as in subjects with a normal neuropathological examination but with a history of T2DM and in a small cohort of control subjects without T2DM. Furthermore, we found amylin deposits in the brain of these subjects, providing histological evidence that amylin can interact with Aß and tau in both the pancreas and hippocampus. INTERPRETATION: The presence of both tau and Aß inclusions in pancreatic ß cells, and of amylin deposits in the brain, provides new evidence of a potential overlap in the mechanisms underlying the pathogenesis of T2DM and AD. ANN NEUROL 2019;86:539-551.

Células no neoplásicas tipo anillo de sello en un adenoma tubular colónico / Non-neoplastic signet- ring cells in a colonic tubular adenoma

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Interaction of amyloidogenic proteins in pancreatic ß cells from subjects with synucleinopathies.

Parkinson's disease patients experience a wide range of non-motor symptoms that may be provoked by deposits of phosphorylated α-synuclein in the peripheral nervous system. Pre-existing diabetes mellitus might be a risk factor for developing Parkinson's disease, and indeed, nearly 60% of Parkinson's disease patients are insulin resistant. Thus, we have investigated whether phosphorylated α-synuclein is deposited in pancreatic tissue of subjects with synucleinopathies. We studied pancreatic tissue from 39 subjects diagnosed with Parkinson's disease, Lewy body Dementia or incidental Lewy bodies disease, as well as that from 34 subjects with diabetes mellitus and a normal neuropathological examination, and 52 subjects with a normal neuropathological examination. We examined the pancreatic accumulation of phosphorylated α-synuclein and of the islet amyloid polypeptide precursor (IAPP), an amyloidogenic protein that plays an unknown role in diabetes mellitus, but that can promote α-synuclein amyloid deposition in vitro. Moreover, we performed proximity ligation assays to assess whether these two proteins interact in the pancreas of these subjects. Cytoplasmic phosphorylated α-synuclein deposits were found in the pancreatic ß cells of 14 subjects with Parkinson's disease (93%), in 11 subjects with Lewy body Dementia (85%) and in 8 subjects with incidental Lewy body disease (73%). Furthermore, we found similar phosphorylated α-synuclein inclusions in 23 subjects with a normal neuropathological examination but with diabetes mellitus (68%) and in 9 control subjects (17%). In addition, IAPP/α-synuclein interactions appear to occur in patients with pancreatic inclusions of phosphorylated α-synuclein. The presence of phosphorylated α-synuclein inclusions in pancreatic ß cells provides a new evidence of a mechanism that is potentially common to the pathogenesis of diabetes mellitus, PD and DLB. Moreover, the interaction of IAPP and α-synuclein in the pancreatic ß cells of patients may represent a novel target for the development of strategies to treat these diseases.

Liver metastasis secondary to primary mesenteric carcinoid.

Carcinoid tumors are rare, slow-growing neoplasms that display neuroendocrine properties. The term carcinoid is generally applied to well-differentiated neoplasms, while neuroendocrine carcinoma is reserved only for poorly differentiated lesions. They can be found throughout the different regions of the gastrointestinal system, although they have predilection for the ileum.

Liver metastasis secondary to primary mesenteric carcinoid

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Ultrasonic Welding of Thermoplastic Composite Coupons for Mechanical Characterization of Welded Joints through Single Lap Shear Testing.

This paper presents a novel straightforward method for ultrasonic welding of thermoplastic-composite coupons in optimum processing conditions. The ultrasonic welding process described in this paper is based on three main pillars. Firstly, flat energy directors are used for preferential heat generation at the joining interface during the welding process. A flat energy director is a neat thermoplastic resin film that is placed between the parts to be joined prior to the welding process and heats up preferentially owing to its lower compressive stiffness relative to the composite substrates. Consequently, flat energy directors provide a simple solution that does not require molding of resin protrusions on the surfaces of the composite substrates, as opposed to ultrasonic welding of unreinforced plastics. Secondly, the process data provided by the ultrasonic welder is used to rapidly define the optimum welding parameters for any thermoplastic composite material combination. Thirdly, displacement control is used in the welding process to ensure consistent quality of the welded joints. According to this method, thermoplastic-composite flat coupons are individually welded in a single lap configuration. Mechanical testing of the welded coupons allows determining the apparent lap shear strength of the joints, which is one of the properties most commonly used to quantify the strength of thermoplastic composite welded joints.

Síndrome de Meckel. Diagnóstico prenatal y diagnóstico diferencial / Meckel syndrome. Prenatal diagnosis and differential diagnosis

El síndrome de Meckel es un infrecuente y letal síndrome polimalformativo de herencia autosómica recesiva. Su incidencia oscila entre 1:1.300 y 1:140.000 nacimientos. Las malformaciones que se observan con más frecuencia son a nivel del sistema nervioso central (frecuentemente meningoencefalocele occipital), displasia renal multiquística bilateral, fibrosis hepática y polidactilia. La alteración genómica que lo produce puede localizarse en diversos loci. El diagnóstico prenatal es posible mediante sospecha ecográfica y, en muchos casos, mediante estudio del ADN fetal. Presentamos el caso de una paciente que tuvo 2 embarazos consecutivos en los que se diagnosticó dicho síndrome (AU)

Meckel syndrome is an infrequent and lethal syndrome characterized by multiple malformations. Inheritance is autosomal recessive. The incidence of this syndrome ranges from 1:1,300 to 1:140,000 births. The most common malformations are those affecting the central nervous system (usually occipital meningoencephalocele), bilateral renal cystic dysplasia, fibrotic changes of the liver and polydactyly. The associated genomic alteration can involve distinct loci. Prenatal diagnosis is feasible with ultrasound findings and, in numerous cases, with fetal DNA analysis. We present the case of a woman who had two consecutive pregnancies with a diagnosis of Meckel syndrome (AU)

Condrosarcoma mesenquimal de nasofaringe y carcinoma de células acinares de la glándula parótida sincrónicos en una niña / Synchronous mesenchymal chondrosarcoma of the nasopharynx and acinic cell carcinoma of the parotid gland in an 11 year old girl

Según nuestro conocimiento, este es el primer caso descrito de un condrosarcoma mesenquimal (CM) nasofaríngeo y un carcinoma de células acinares (CCA) de la glándula parótida síncronos en una niña de 11 años. El CM es un sarcoma de alto grado de comportamiento clínico agresivo, con gran tendencia a las recidivas tardías y a metastatizar. Es un tumor bifásico constituido por áreas de células pequeñas e indiferenciadas, entremezcladas con islotes de cartílago hialino.Típicamente ocurre en adultos jóvenes y el tratamiento consiste en su extirpación con márgenes amplios. El CCA es un tumor maligno de glándulas salivares poco frecuente.La presencia de gránulos citoplasmáticos de zimógeno (PAS +) es muy específica de esta entidad.Puede afectar a pacientes de cualquier edad. Según publicaciones recientes, el pronóstico de los tumores malignos de glándula salivar en la población infantil es bueno(AU)

We present a case of synchronous mesenchymal chondrosarcoma (MC) of the nasopharyx and acinic cell carcinoma (AAC) of the parotid gland in an 11 year old girl. To our knowledge, this is the first time this has been reported.MC is a high grade sarcoma which is highly aggressive clinically and has a strong tendency towards late recurrences and distant metastases. Morphologically, it is a biphasic tumour made up of areas of small, round, undifferentiated cells intermixed with islands of hyaline cartilage. Typically, it occurs in young adults and requires surgical excision with wide margins. AAC is an unusual malignant salivary gland neoplasm which can affect a wide age range of patients, from young children to adults. PAS positive cytoplasmic zymogen granules are highly specific for AAC. According to recent studies, malignant salivary gland neoplasms in paediatric patients have a good prognosis(AU)