Lower respiratory tract infections, including chronic obstructive pulmonary disease exacerbations (COPD-E) and community acquired pneumonia (CAP), are one of the most frequent reasons for ...consultation in primary care and hospital emergency departments, and are the cause of a high prescription of antimicrobial agents. The selection of the most appropriate oral antibiotic treatment is based on different aspects and includes to first consider a bacterial aetiology and not a viral infection, to know the bacterial pathogen that most frequently cause these infections and the frequency of their local antimicrobial resistance. Treatment should also be prescribed quickly and antibiotics should be selected among those with a quicker mode of action, achieving the greatest effect in the shortest time and with the fewest adverse effects (toxicity, interactions, resistance and/or ecological impact). Whenever possible, antimicrobials should be rotated and diversified and switched to the oral route as soon as possible. With these premises, the oral treatment guidelines for mild or moderate COPD-E and CAP in Spain include as first options beta-lactam antibiotics (amoxicillin and amoxicillin-clavulanate and cefditoren), in certain situations associated with a macrolide, and relegating fluoroquinolones as an alternative, except in cases where the presence of Pseudomonas aeruginosa is suspected.
The addition of atezolizumab (anti–PD-L1 antibody) to a platinum-based chemotherapy regimen improved progression-free survival among patients who had not previously received chemotherapy for ...metastatic NSCLC, regardless of PD-L1 expression and
EGFR
or
ALK
genomic alteration status.
Adenocarcinomas of the pancreatobiliary system are currently classified by their primary anatomical location. In particular, the pathological diagnosis of intrahepatic cholangiocarcinoma is still ...considered as a diagnosis of exclusion of metastatic adenocarcinoma. Periampullary cancers have been previously classified according to the histological type of differentiation (pancreatobiliary, intestinal), but overlapping morphological features hinder their differential diagnosis. We performed an integrative immunohistochemical analysis of pancreato-biliary tumors to improve their diagnosis and prediction of outcome.
This was a retrospective observational cohort study on patients with adenocarcinoma of the pancreatobiliary system who underwent diagnostic core needle biopsy or surgical resection at a tertiary referral center. 409 tumor samples were analyzed with up to 27 conventional antibodies used in diagnostic pathology. Immunohistochemical scoring system was the percentage of stained tumor cells. Bioinformatic analysis, internal validation, and survival analysis were performed.
Hierarchical clustering and differential expression analysis identified three immunohistochemical tumor types (extrahepatic pancreatobiliary, intestinal, and intrahepatic cholangiocarcinoma) and the discriminant markers between them. Among patients who underwent surgical resection of their primary tumor with curative intent, the intestinal type showed an adjusted hazard ratio of 0.19 for overall survival (95% confidence interval 0.05-0.72; p value = 0.014) compared to the extrahepatic pancreatobiliary type.
Integrative immunohistochemical classification of adenocarcinomas of the pancreatobiliary system results in a characteristic immunohistochemical profile for intrahepatic cholangiocarcinoma and intestinal type adenocarcinoma, which helps in distinguishing them from metastatic and pancreatobiliary type adenocarcinoma, respectively. A diagnostic immunohistochemical panel and additional extended panels of discriminant markers are proposed as guidance for their pathological diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Cow's milk allergy (CMA) affects 2.5% of young infants. In previous murine studies it was observed that allergic sensitization to the major cow's milk allergens casein and whey led, ...respectively, to IgE-independent and IgE-dependent clinical responses. Objectives In this study the involvement of immunoglobulin free light chains (Ig-fLCs) in the hypersensitivity response to cow's milk proteins was explored in mice, and Ig-fLC serum levels were determined in children affected by CMA or atopic dermatitis (AD). Methods Mice were orally sham, casein, or whey sensitized. Acute allergen-specific skin responses were determined, and serum immunoglobulin and Ig-fLC concentrations were measured. Ig-fLC dependency was validated by using the Ig-fLC blocker F991 in actively and passively sensitized mice. Ig-fLC serum concentrations were measured in a cohort of infants with CMA and infants with AD. Results After sensitization, no specific IgE was detectable in sera of casein-sensitized mice, whereas specific IgE levels were enhanced in whey-sensitized mice. Instead, Ig-fLC levels were increased in sera from casein-sensitized mice. Furthermore, blocking Ig-fLCs strongly diminished the allergic skin responses not only in casein-sensitized mice but also in mice transferred with splenocyte supernatants of casein-sensitized mice. In both patients with CMA and patients with AD, serum Ig-fLC concentrations were significantly enhanced. Conclusions This study indicates that sensitization with cow's milk proteins can lead to both IgE-dependent and Ig-fLC–dependent allergic hypersensitivity responses. Also, in children affected with CMA or AD, serum Ig-fLC concentrations were increased, implying the relevance of Ig-fLC measurements in the diagnoses of human allergic disease.
Deficits in memory and executive performance are well-established features of bipolar disorder and schizophrenia. By contrast, data on cognitive impairment in schizoaffective disorder are scarce and ...the findings are conflicting.
We used the Wechsler Memory Scale (WMS-III) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and executive function in 45 schizophrenic patients, 26 schizomanic patients and 51 manic bipolar patients in comparison to 65 healthy controls. The patients were tested when acutely ill.
All three patient groups performed significantly more poorly than the controls on global measures of memory and executive functioning, but there were no differences among the patient groups. There were few differences in memory and executive function subtest scores within the patient groups. There were no differences in any test scores between manic patients with and without psychotic symptoms.
Schizophrenic, schizomanic and manic patients show a broadly similar degree of executive and memory deficits in the acute phase of illness. Our results do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits.
To evaluate the sensitivity of sympathetic skin response (SSR) and compare it with scintigraphy in patients with complex regional pain syndrome diagnosed according to the Budapest criteria.
...Twenty-two patients with complex regional pain syndrome who attended the Rehabilitation and Physical Medicine Department between January-2018 and May-2022 have been prospectively evaluated. The scintigraphy was considered positive if in the 1st-2nd phase slight asymmetric and diffuse uptake was observed, or when in the 3rd phase marked periarticular radioisotope uptake was observed. SSR was abnormal if: a) no response after 20 stimuli; b) lack of habituation with permanence of the stimuli greater than 67.2%.
Age 55.4±8.57 years. Complex regional pain syndrome was more frequent in women (90.9%), more common in upper limbs (68.2%) than lower limbs (31.8%). In SSR, we have observed normal response (<67.2%) in 2 patients (11.1%), lack of SSR in 2 patients (11.1%) and lack of habituation (>67.2%) in 14 patients (77.8%). In total, 16 patients presented abnormal or absent responses (88.8%). The diagnostic sensitivity of scintigraphy is similar to that of SSR (89.5% vs 88.8%), with no statistical difference (P=.6721).
Scintigraphy has shown similar sensitivity to SSR, although the simplicity, security, low cost, non-ionizing and non-invasiveness of the latter technique suggest that it could be more cost-effective. The lack of habituation and the absence of response could identify response patterns and localize the involvement in the afferent, central, efferent or post-ganglionic pathways.
RESUMEN Introducción: La osteoartritis (OA) es la causa más común de la artritis. Tradicionalmente, la OA se consideraba como una enfermedad de "desgaste". Sin embargo, los factores metabólicos e ...inflamatorios se están considerando ahora como los factores patogénicos hasta el punto de que algunos autores están redefiniendo la OA como una enfermedad de "inflamación crónica de bajo grado". Evidencia: En la artrosis de rodilla están involucradas muchas vías de señalización y mediadores inflamatorios. El nuevo paradigma de tratamiento se basa en los tratamientos celulares sobre las vías de señalización de la inflamación, basados en componentes celulares y proteicos para combatir el entorno inflamatorio de la articulación artrósica y regenerar el tejido dañado. Resultados: El enfoque de tratar solo una diana terapéutica (inhibidores de óxido nítrico, nutracéuticos, agentes reductores de uratos y fármacos biológicos) que han demostrado su eficacia en el tratamiento de enfermedades inflamatorias como la artritis reumatoide no se ha traducido en un manejo eficaz de la OA. Un enfoque de tratamiento dirigido simultáneamente a varias dianas sería capaz de manejar la OA de manera más eficiente. Las pautas estándar (AAOS, OARSI, ACR, NICE o EULAR) no consideran el ácido hialurónico, el plasma rico en plaquetas ni el ozono, aunque estas opciones de tratamiento han mostrado propiedades inmunomoduladoras y curativas. En ese escenario, planteamos la hipótesis de que el ácido hialurónico, el plasma rico en plaquetas y el ozono son alternativas prometedoras para el manejo de la OA de rodilla, debido a sus propiedades multidiana, como se observará en esta revisión. Conclusión: En el presente estudio se ha revisado la fisiopatología de la OA, centrándose principalmente en el mecanismo inflamatorio, las vías de señalización implicadas y los posibles objetivos del tratamiento. El ácido hialurónico, el plasma rico en plaquetas y el ozono se postulan como opciones de tratamiento multidiana para el tratamiento de la artrosis de rodilla.
The identification of immunophenotypic aberrancies through multiparametric flow cytometry makes the differentiation between normal and leukemic cells relatively simple and quick, and is therefore an ...attractive method for the investigation of minimal residual disease (MRD). In this report, we have analyzed the impact on relapse and relapse-free survival (RFS) of detecting immunophenotypical aberrant cells in acute lymphoblastic leukemia (ALL) patients in cytomorphologic complete remission (CR).
Two hundred eleven bone marrow (BM) samples from 53 consecutive ALL (37 precursor B-ALL and 16 T-ALL) patients were analyzed. The only selection criteria were to have at least one aberrant immunophenotypic feature at diagosis and to have achieved cytomorphologic CR after induction therapy. For MRD detection, all follow-up samples were analyzed with triple labelings using a two-step acquisition procedure, in which 106 cells were screened for the possible persistence of residual leukemic cells with the same phenotypic aberrancy as that identified diagnosis.
Patients who displayed a gradual increase in MRD levels showed a higher relapse rate (90% v22%; P < .00001) and shorter median RFS (12 months v not reached; P < .0001) than those with stable or decreasing MRD levels. This adverse prognostic influence also was observed when children and adults, as well as B-ALL and T-ALL patients, were analyzed separately. An MRD level > or = or greater than 10(-3) discriminated two risk groups of ALL patients with significantly different relapse rates and RFS at all treatment phases (end of induction, consolidation, maintenance, and out of treatment).
Multiparametric flow cytometry of MRD in ALL patients is a valuable tool for relapse prediction and for the identification of a cohort of patients with very poor prognosis.
The CONNIE Experiment (Coherent Neutrino Nucleus Interaction Experiment) is currently collecting reactor neutrino data to search for the undiscovered standard model process of coherent ...neutrino-nucleus scattering (CNNS). The detector is composed of a silicon target of thick, fully-depleted, low-noise CCD detectors. Results from data collected in 2015 indicate backgrounds are controlled, and allow an estimate of sensitivity to be presented for a larger scale detector. A 2016 upgrade, adding additional target mass, and reducing readout noise, has been performed, increasing the total yield of signal events by a factor of 30, and already yielding science-quality data. Low-energy nuclear calibrations have been performed, enabling calibration down to the device energy threshold. An estimate of the sensitivity expected for measuring the coherent neutrino process is presented. Future prospects with improved detector energy thresholds are estimated.
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