Viage de España, en que se da noticia de las cosas mas apreciables, y dignas de saberse, que hay en ella. Tomo decimo

Marca tip. en portSign.: a-c8, A-R8, S4Entre p. 68 y 69 grab. calc.: "D. Iñigo Lopez de Mendoza Primer Marques de Santillana, I. Barcelon lo grabó

Clinical usefulness of scoring systems to predict severe acute pancreatitis : A systematic review and meta-analysis with pre and post-test probability assessment

Scoring systems for severe acute pancreatitis (SAP) prediction should be used in conjunction with pre-test probability to establish post-test probability of SAP, but data of this kind are lacking.To investigate the predictive value of commonly employed scoring systems and their usefulness in modifying the pre-test probability of SAP.Following PRISMA statement and MOOSE checklists after PROSPERO registration, PubMed was searched from inception until September 2022. Retrospective, prospective, cross-sectional studies or clinical trials on patients with acute pancreatitis defined as Revised Atlanta Criteria, reporting rate of SAP and using at least one score among Bedside Index for Severity in Acute Pancreatitis (BISAP), Acute Physiology and Chronic Health Examination (APACHE)-II, RANSON, and Systemic Inflammatory Response Syndrome (SIRS) with their sensitivity and specificity were included. Random effects model meta-analyses were performed. Pre-test probability and likelihood ratio (LR) were combined to estimate post-test probability on Fagan nomograms. Pooled severity rate was used as pre-test probability of SAP and pooled sensitivity and specificity to calculate LR and generate post-test probability. A priori hypotheses for heterogeneity were developed and sensitivity analyses planned.43 studies yielding 14,116 acute pancreatitis patients were included: 42 with BISAP, 30 with APACHE-II, 27 with Ranson, 8 with SIRS. Pooled pre-test probability of SAP ranged 16.6%-25.3%. The post-test probability of SAP with positive/negative score was 47%/6% for BISAP, 43%/5% for APACHE-II, 48%/5% for Ranson, 40%/12% for SIRS. In 18 studies comparing BISAP, APACHE-II, and Ranson in 6740 patients with pooled pre-test probability of SAP of 18.7%, post-test probability when scores were positive was 48% for BISAP, 46% for APACHE-II, 50% for Ranson. When scores were negative, post-test probability dropped to 7% for BISAP, 6% for Ranson, 5% for APACHE-II. Quality, design, and country of origin of the studies did not explain the observed high heterogeneity.The most commonly used scoring systems to predict SAP perform poorly and do not aid in decision-making

Endoscopical and pathological dissociation in severe colitis induced by immune-checkpoint inhibitors

Checkpoint inhibitors have improved the survival of patients with advanced tumors and show a manageable toxicity profile. However, auto-immune colitis remains a relevant side effect, and combinations of anti-PD1/PDL1 and anti-CTLA-4 increase its incidence and severity. Here, we report the case of a 50-year-old patient diagnosed with stage IV cervical cancer that relapsed following radical surgery, external radiation/brachytherapy and standard chemotherapy. She was subsequently treated with Nivolumab and Ipilimumab combination and developed grade 2 colitis presenting a dissociation between endoscopic and pathological findings. At cycle 10 the patient reported grade 3 diarrhea and abdominal discomfort, without blood or mucus in the stools. Immunotherapy was withheld and a colonoscopy was performed, showing normal mucosa in the entire colon. Puzzlingly, histologic evaluation of randomly sampled mucosal biopsy of the distal colon showed an intense intraepithelial lymphocyte infiltration with crypt loss and some regenerating crypts with a few apoptotic bodies set in a chronically inflamed lamina propria, consistent with the microscopic diagnosis of colitis. Treatment with methylprednisolone 2 mg/kg was initiated which led to a decrease in the number of stools to grade 1. Additional investigations to exclude other causes of diarrhea rendered negative results. The patient experienced a major partial response and, following the resolution of diarrhea, she was re-challenged again with immunotherapy, with the reappearance of grade 2 diarrhea, leading to permanent immunotherapy interruption. We conclude and propose that performing random colonic biopsies should be considered in cases of immune checkpoint-associated unexplained diarrhea, even when colonoscopy shows macroscopically normal colonic mucosa inflammatory lesions

Impacto en los tiempos puerta-aguja de un conjunto de medidas para optimizar la atención hospitalaria del código ictus

Introducción: El tiempo sigue siendo una variable determinante para los tratamientos de reper-fusión del ictus isquémico agudo. A pesar de las recomendaciones de las guías clínicas, soloalrededor de la tercera parte de los pacientes con ictus isquémico agudo son fibrinolizadosen = 60 min. El objetivo de este trabajo es describir nuestra experiencia implementando unprotocolo específico de atención del ictus isquémico agudo y evaluar su impacto en nuestrostiempos puerta-aguja. Métodos: A finales del 2015, se implantaron gradualmente unas medidas dise ~nadas para acortarlos tiempos de actuación y optimizar la atención del ictus isquémico agudo incluyendo unaguardia específica de Neurovascular. Se compararon los tiempos de actuación antes (2013-2015)y después (2017-2019) de la introducción de este protocolo. Resultados: Se incluyó a 182 pacientes antes y 249 después de la intervención. Cuando todas lasmedidas fueron introducidas, la mediana global de tiempo puerta-aguja fue de 45 min (previa74 min, 39% menos, p < 0, 001) con un 73, 5% de pacientes tratados en = 60 min (47% más quepreintervención, p < 0, 001). El tiempo global al tratamiento (inicio síntoma-aguja) se redujo en20 min de mediana (p < 0, 001). Conclusiones: Las medidas asociadas en nuestro protocolo han conseguido una disminución deltiempo puerta-aguja de forma significativa y sostenida, aunque todavía nos queda margen demejora, la dinámica establecida de control de resultados y mejora continua hará posible seguiravanzando en este sentido. Introduction: Time continues to be a fundamental variable in reperfusion treatments for acute ischaemic stroke. Despite the recommendations made in clinical guidelines, only around one-third of these patients receive fibrinolysis within 60 minutes. In this study, we describe our experience with the implementation of a specific protocol for patients with acute ischaemic stroke and evaluate its impact on door-to-needle times in our hospital. Methods: Measures were gradually implemented in late 2015 to shorten stroke management times and optimise the care provided to patients with acute ischaemic stroke; these measures included the creation of a specific on-call neurovascular care team. We compare stroke management times before (2013-2015) and after (2017-2019) the introduction of the protocol. Results: The study includes 182 patients attended before implementation of the protocol and 249 attended after. Once all measures were in effect, the overall median door-to-needle time was 45 minutes (vs 74 minutes before, a 39% reduction; P<.001), with 73.5% of patients treated within 60 minutes (a 47% increase; P<.001). Median overall time to treatment (onset-to-needle time) was reduced by 20 minutes (P<.001). Conclusions: The measures included in our protocol achieved a significant, sustained reduction in door-to-needle times, although there remains room for improvement. The mechanisms established for monitoring outcomes and for continuous improvement will enable further advances in this regard

Cytokines in clinical cancer immunotherapy

Cytokines are soluble proteins that mediate cell-to-cell communication. Based on the discovery of the potent anti-tumour activities of several pro-inflammatory cytokines in animal models, clinical research led to the approval of recombinant interferon-alpha and interleukin-2 for the treatment of several malignancies, even if efficacy was only modest. These early milestones in immunotherapy have been followed by the recent addition to clinical practice of antibodies that inhibit immune checkpoints, as well as chimeric antigen receptor T cells. A renewed interest in the anti-tumour properties of cytokines has led to an exponential increase in the number of clinical trials that explore the safety and efficacy of cytokine-based drugs, not only as single agents, but also in combination with other immunomodulatory drugs. These second-generation drugs under clinical development include known molecules with novel mechanisms of action, new targets, and fusion proteins that increase half-life and target cytokine activity to the tumour microenvironment or to the desired effector immune cells. In addition, the detrimental activity of immunosuppressive cytokines can be blocked by antagonistic antibodies, small molecules, cytokine traps or siRNAs. In this review, we provide an overview of the novel trends in the cytokine immunotherapy field that are yielding therapeutic agents for clinical trials

Processing of Thionin Precursors in Barley Leaves by a Vacuolar Proteinase

Thionins are synthesized as precursors with a signal peptide and a long C-terminal acidic peptide that is post-translationally processed. A fusion protein including the maltose-binding protein from Eschrrichia coli (MalE), thionin DG3 froin barley leaves, and its acidic C-terminal peptide has been used to obtain antibodies that recognize both domains of the precursor. In barley leaf sections. mature thionins accuinulated in the vacuolar content, while the acidic peptide was not detected in any cell fraction. Brefeldin A and inonensin inhibited processing of the precursor but its export from the microsomal fraction was not inhibited. Both purified vacuoles aiid an acid (pH 5.5) extract from leaves processed the fusion protein into a MalE-thionin and an acidic peptide fragment. A 70-kDa proteinase that effected this cleavage was purified froin the acid extract. Processing of the fusion protein by both lysed vacuoles and the purified proteinase was inhibited by Zn2+ and by Cu2+, but not by inhibitors of the previously described vacuolar processing thiol or aspartic proteinases. In vivo processing of the thionin precursor in leaf sections was also inhibited by Zn+, and Cu2+, Variants of the fusion protein with altered processing sites that represented thme of thionin precursors from different taxa were readily processed by the proteinase, whereas changing the polarity of either the C-terminal or N-terminal residues of the processing site prevented cleavage by the proteinase

Genetic testing among high-risk individuals in families with hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is frequently associated with constitutional mutations in a class of genes involved in DNA mismatch repair. We identified 32 kindreds, with germline mutations in one of three genes hMSH2, hMLH1 or hMSH6. In this study, we purposed to evaluate how many high-risk individuals in each family underwent genetic testing: moreover, we assessed how many mutation-positive unaffected individuals accepted colonoscopic surveillance and the main findings of the recommended follow-up. Families were identified through a population-based registry, or referred from other centres. Members of the families were invited for an education session with two members of the staff. When a kindred was consistent with HNPCC, neoplastic tissues were examined for microsatellite instability (MSI) and immunohistochemical expression of MSH2, MLH1 and MSH6 proteins. Moreover, constitutional mutations were searched by SSCP or direct sequencing of the whole genomic region. Of the 164 subjects assessed by genetic testing, 89 were gene carriers (66 affected - that is, with HNPCC-related cancer diagnosis - and 23 unaffected) and 75 tested negative. Among the 23 unaffected gene carriers, 18 (78.3%) underwent colonoscopy and four declined. On a total of 292 first degree at risk of cancer, 194 (66.4%) did not undergo genetic testing. The main reasons for this were: (a) difficulty to reach family members at risk, (b) lack of collaboration, (c) lack of interest in preventive medicine or 'fatalistic' attitude towards cancer occurrence. The number of colorectal lesions detected at endoscopy in gene carriers was significantly (P<0.01) higher than in controls (noncarriers). We conclude that a large fraction of high-risk individuals in mutation-positive HNPCC families does not undergo genetic testing, despite the benefits of molecular screening and endoscopic surveillance. This clearly indicates that there are still barriers to genetic testing in HNPCC, and that we are unable to provide adequate protection against cancer development in these families

Patterns of change in treatment, response, and outcome in patients with follicular lymphoma over the last four decades: a single-center experience.

Although the introduction of immunotherapy has improved outcomes for follicular lymphoma (FL) patients, histological transformation (HT) and early relapse still confer a poor prognosis. We sought to describe the patterns of change in treatment, response, and outcome of FL patients at our institution over the last four decades. Seven hundred and twenty-seven patients (389 F/338 M; median age, 57 years) consecutively diagnosed with grade 1-3a FL between 1980 and 2017, categorized into four decades according to the time of diagnosis, constituted the study population. Clinical characteristics, treatment, response, absolute and relative survival, HT, second malignancies (SM), and causes of death were assessed. Median OS for the entire cohort was 17.6 years. From decade 1 to 4, there was an increase in the complete response rate (48 to 70%), progression-free survival (40 to 56% at 5 years), OS (77 to 86% at 5 years), and relative survival ratio (0.83 to 0.94 at 5 years), with no significant differences in the risk of HT or SM. Lymphoma remained the most common cause of death in all four decades. These findings illustrate the overall improvement in outcome for FL patients, but support the need for further research into risk stratification and management

Tratamiento endovascular del ictus isquémico vertebrobasilar en Aragón: características clínicas, radiológicas, tiempos de atención y pronóstico a los 3 meses

Introducción: Los ictus de circulación posterior suponen el 15-20% del total de los ictus isquémicos, pero asocian en más del 60% de los casos mal pronóstico funcional y vital. Por sus características clínicas y radiológicas, su diagnóstico y manejo son más complejos que los de los ictus de circulación anterior. El objetivo de nuestro trabajo es analizar a los pacientes con ictus del sistema vertebrobasilar tratados con trombectomía mecánica en nuestra comunidad y definir sus características. Método: Análisis retrospectivo-descriptivo de los pacientes con ictus del sistema vertebrobasilar tratados mediante trombectomía mecánica en nuestro centro (hospital de referencia para la enfermedad cerebrovascular urgente en Aragón). Se definen características basales, factores de riesgo, signos y síntomas de presentación, escalas radiológicas, variables del procedimiento, tiempos de atención y pronóstico funcional a los 3 meses. Resultados: Se incluyó a 37 pacientes (39,5% mujeres) con una edad media de 68,34 ± 14,1 años. La primera causa etiológica fue la cardioembólica (42,1%), seguida de la aterotrombótica (28,9%). La localización más frecuente de la obstrucción fue el top de la basilar (55,3%). Los síntomas más frecuentes fueron somnolencia (76,3%), déficit motor (71,1%) y náuseas (55,3%). Se logró reperfusión exitosa (mTICIx ≥ 2b) en el 81,1% de pacientes. El pronóstico funcional a 90 días fue desfavorable (mRS < 3) en el 59% de los casos. Conclusiones: Los ictus de circulación posterior se asocian a una importante morbimortalidad. Su presentación clínica subaguda y larvada dilata los tiempos de atención y dificulta una identificación precoz. La trombectomía mecánica es un procedimiento seguro y eficaz, si bien son necesarios más estudios que esclarezcan la selección de pacientes. Introduction: Posterior circulation stroke accounts for 15%-20% of ischaemic strokes, but is associated with poor functional and vital prognosis in over 60% of cases. Due to its clinical and radiological peculiarities, diagnosis and management are more complex than in anterior circulation stroke. This study analyses and characterises patients with vertebrobasilar strokes treated with mechanical thrombectomy in our region. Methods: We conducted a descriptive, retrospective analysis of patients with vertebrobasilar stroke and treated with mechanical thrombectomy at our centre, a reference centre for cerebrovascular emergencies for the region of Aragon. We recorded baseline characteristics, risk factors, signs and symptoms at onset, radiological assessment scale scores, procedure-related variables, management times, and functional prognosis at 3 months. Results: We selected 37 patients (39.5% women; mean age [standard deviation], 68.34 [14.1] years). Cardioembolic stroke (42.1%) was the most common aetiology, followed by atherothrombosis (28.9%). The top of the basilar artery was the most common site of obstruction (55.3%). The most frequent clinical features were somnolence (76.3%), motor deficits (71.1%), and nausea (55.3%). Successful reperfusion (mTICI ≥ 2b) was achieved in 81.1% of patients. Functional outcome at 90 days was poor (mRS < 3) in 59% of patients. Conclusions: Posterior circulation stroke is associated with high rates of morbidity and mortality. Its subacute, nonspecific clinical course prolongs management times and hinders early detection. Mechanical thrombectomy is a safe and effective procedure, although further studies are needed to establish the optimal patient profile

A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis

Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival –DFS-) 25.26 months, 95% CI 8. 74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32–18.88)