Randomized phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer.

OBJECTIVE: Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. The aim was to establish the role of nintedanib in addition to paclitaxel and carboplatin in first-line recurrent/metastatic cervical cancer. METHODS: Double-blind phase II randomized study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin-paclitaxel with oral nintedanib 200 mg BID/placebo. The primary endpoint was progression-free survival (PFS) at 1.5 years and α = 0.15, ß = 80%, one sided. RESULTS: 120 patients (62 N, 58C) were randomized. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favor of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However, N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Global health status during and at the end of the study was similar in both arms. CONCLUSION: The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.

Not all autoantibodies are clinically relevant. Classic and novel autoantibodies in Sjögren's syndrome: A critical review.

Sjögren's syndrome (SjS) is a heterogeneous systemic disease. The abnormal responses to La/SSB and Ro/SSA of both B-cells and T-cells are implicated as well as others, in the destruction of the epithelium of the exocrine glands, whose tissue characteristically shows a peri-epithelial lymphocytic infiltration that can vary from sicca syndrome to systemic disease and lymphoma. Despite the appearance of new autoantibodies, anti-Ro/SSA is still the only autoantibody included in the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria and is used extensively as a traditional biomarker in clinical practice. The study and findings of new autoantibodies in SjS has risen in the previous decade, with a central role given to diagnosis and elucidating new aspects of SjS physiopathology, while raising the opportunity to establish clinical phenotypes with the goal of predicting long-term complications. In this paper, we critically review the classic and the novel autoantibodies in SjS, analyzing the methods employed for detection, the pathogenic role and the wide spectrum of clinical phenotypes.

Clinical and radiological findings for the new multisystem inflammatory syndrome in children associated with COVID-19.

The World Health Organization defines the multisystem inflammatory syndrome in children (MIS-C) as a new syndrome reported in patients aged <19 years old who have a history of exposure to SARS-CoV-2. The onset of this syndrome is characterized by persistent fever that is associated with lethargy, abdominal pain, vomiting and/or diarrhea, and, less frequently, rash and conjunctivitis. The course and severity of the signs and symptoms vary; in some children, MIS-C worsens rapidly and can lead to hypotension, cariogenic shock, or even damage to multiple organs. The characteristic laboratory findings are elevated markers of inflammation and heart dysfunction. The most common radiological findings are cardiomegaly, pleural effusion, signs of heart failure, ascites, and inflammatory changes in the right iliac fossa. In the context of the current COVID-19 pandemic, radiologists need to know the clinical, laboratory, and radiological characteristics of this syndrome to ensure the correct diagnosis.

[Clinical and radiological findings for the new multisystem inflammatory syndrome in children associated with COVID-19]. / Revisión de los hallazgos clínicos y radiológicos del nuevo síndrome inflamatorio multisistémico pediátrico vinculado a la COVID-19.

The World Health Organization defines the multisystem inflammatory syndrome in children (MIS-C) as a new syndrome reported in patients aged < 19 years old who have a history of exposure to SARS-CoV-2. The onset of this syndrome is characterized by persistent fever that is associated with lethargy, abdominal pain, vomiting and/or diarrhea, and, less frequently, rash and conjunctivitis. The course and severity of the signs and symptoms vary; in some children, MIS-C worsens rapidly and can lead to hypotension, cariogenic shock, or even damage to multiple organs. The characteristic laboratory findings are elevated markers of inflammation and heart dysfunction. The most common radiological findings are cardiomegaly, pleural effusion, signs of heart failure, ascites, and inflammatory changes in the right iliac fossa. In the context of the current COVID-19 pandemic, radiologists need to know the clinical, laboratory, and radiological characteristics of this syndrome to ensure the correct diagnosis.

[Alteration of X-ray measurements in proximal humerus osteosynthesis with intramedullary nail]. / Alteración de mediciones radiográficas en osteosíntesis de húmero proximal con clavo centromedular.

INTRODUCTION: The quality of reduction in proximal humerus fractures is valuable with radiographic criteria (Neck-shaft angle [NSA]; medial offset [MO]; distance head tuberosity [DHT] and subacromial space [SS]) that predict functionality. These criteria set for other implants are not described for the intramedullary nail. MATERIAL AND METHODS: Observational cohort study, retrospective, with patients 18 years, with osteosynthesis with intramedullary nail (2014 to 2017), evaluating demographic characteristics, severity of injury (Neer classification), progressive radiographic measurements and complications. RESULTS: 84 cases with an average age of 65 ± 2 years and an average follow-up of 13.9 months were analyzed. By Neer rating 40.4% were grade II, 29.7% grade III and 29.7% grade IV. Consolidation in varus increases to 10.7% at the end of follow-up, with Neer III and IV patients. The 140° deformity is prevalent for Neer II (n = 15/34). 30.9% have a change of neck-shaft angle of 10°. Overall 86.9% has HTD changes 5 mm. Cases Neer III/IV 32% has alteration of SS 5 mm. The most common complication is avascular necrosis (AVN) with 44% of cases. CONCLUSIONS: Radiographic measurements have changes in long-term follow-up. Alterations in NSA ( 10o) and SS ( 5 mm) occur in higher proportion of Neer III/IV patients, according to the severity of the fracture, favoring vicious consolidations in varus or valgus and increased presence of AVN.

INTRODUCCIÓN: La calidad de reducción en las fracturas de húmero proximal es posible valorarla a través de criterios radiográficos (ACD = ángulo cervicodiafisario; OM = offset medial; DTC = distancia tuberosidad-cabeza y ES = espacio subacromial), los cuales predicen la funcionalidad. Sin embargo, estos criterios establecidos para otros implantes no están descritos para el clavo centromedular. MATERIAL Y MÉTODOS: Estudio de cohorte observacional y retrospectivo en pacientes 18 años con osteosíntesis con clavo centromedular (durante el período de 2014 a 2017), en donde se evaluaron las características demográficas, severidad de lesión (clasificación de Neer) y las mediciones radiográficas progresivas y complicaciones. RESULTADOS: Se analizaron 84 casos, cuya edad en promedio fue de 65 ± 2 años y la media de seguimiento de 13.9 meses. Por clasificación de Neer: 40.4% fueron grado II; 29.7%, grado III y 29.7%, grado IV. La consolidación en varo aumenta 10.7% al final del seguimiento, siendo aquellos pacientes Neer grado III y IV los más frecuentes. La deformidad 140° predomina para Neer grado II (n = 15/34). En 30.9%, se presenta un cambio de ACD (ACD) 10°. En general, 86.9% tiene cambios de DTC 5 mm. En los casos Neer grado III/IV, 32% tiene una alteración de ES 5 mm. La complicación más frecuentemente es la necrosis avascular (NAV) con 44% de los casos. CONCLUSIONES: Las mediciones radiográficas presentan cambios en valoraciones a largo plazo. Las alteraciones en ACD ( 10o) y ES ( 5 mm) se dan en mayor proporción en aquellos pacientes Neer grado III/IV (acorde con la severidad de la fractura), lo que favorece consolidaciones viciosas en varo o valgo y una mayor presencia de NAV.

Alteración de mediciones radiográficas en osteosíntesis de húmero proximal con clavo centromedular / Alteration of X-ray measurements in proximal humerus osteosynthesis with intramedullary nail

Resumen: Introducción: La calidad de reducción en las fracturas de húmero proximal es posible valorarla a través de criterios radiográficos (ACD = ángulo cervicodiafisario; OM = offset medial; DTC = distancia tuberosidad-cabeza y ES = espacio subacromial), los cuales predicen la funcionalidad. Sin embargo, estos criterios establecidos para otros implantes no están descritos para el clavo centromedular. Material y métodos: Estudio de cohorte observacional y retrospectivo en pacientes > 18 años con osteosíntesis con clavo centromedular (durante el período de 2014 a 2017), en donde se evaluaron las características demográficas, severidad de lesión (clasificación de Neer) y las mediciones radiográficas progresivas y complicaciones. Resultados: Se analizaron 84 casos, cuya edad en promedio fue de 65 ± 2 años y la media de seguimiento de 13.9 meses. Por clasificación de Neer: 40.4% fueron grado II; 29.7%, grado III y 29.7%, grado IV. La consolidación en varo aumenta 10.7% al final del seguimiento, siendo aquellos pacientes Neer grado III y IV los más frecuentes. La deformidad > 140o predomina para Neer grado II (n = 15/34). En 30.9%, se presenta un cambio de ACD (ΔACD) ≥ 10o. En general, 86.9% tiene cambios de DTC < 5 mm. En los casos Neer grado III/IV, 32% tiene una alteración de ES > 5 mm. La complicación más frecuentemente es la necrosis avascular (NAV) con 44% de los casos. Conclusiones: Las mediciones radiográficas presentan cambios en valoraciones a largo plazo. Las alteraciones en ACD (> 10o) y ES (> 5 mm) se dan en mayor proporción en aquellos pacientes Neer grado III/IV (acorde con la severidad de la fractura), lo que favorece consolidaciones viciosas en varo o valgo y una mayor presencia de NAV.

Abstract: Introduction: The quality of reduction in proximal humerus fractures is valuable with radiographic criteria (Neck-shaft angle [NSA]; medial offset [MO]; distance head tuberosity [DHT] and subacromial space [SS]) that predict functionality. These criteria set for other implants are not described for the intramedullary nail. Material and methods: Observational cohort study, retrospective, with patients > 18 years, with osteosynthesis with intramedullary nail (2014 to 2017), evaluating demographic characteristics, severity of injury (Neer classification), progressive radiographic measurements and complications. Results: 84 cases with an average age of 65 ± 2 years and an average follow-up of 13.9 months were analyzed. By Neer rating 40.4% were grade II, 29.7% grade III and 29.7% grade IV. Consolidation in varus increases to 10.7% at the end of follow-up, with Neer III and IV patients. The >140o deformity is prevalent for Neer II (n = 15/34). 30.9% have a change of neck-shaft angle of ≥ 10o. Overall 86.9% has HTD changes < 5 mm. Cases Neer III/IV 32% has alteration of SS > 5 mm. The most common complication is avascular necrosis (AVN) with 44% of cases. Conclusions: Radiographic measurements have changes in long-term follow-up. Alterations in NSA (> 10o) and SS (> 5 mm) occur in higher proportion of Neer III/IV patients, according to the severity of the fracture, favoring vicious consolidations in varus or valgus and increased presence of AVN.

Review of concepts in therapeutic decision-making in HER2-negative luminal metastatic breast cancer.

PURPOSE: Hormone receptor (HR)-positive, Human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) requires a therapeutic approach that takes into account multiple factors, with treatment being based on anti-estrogen hormone therapy (HT). As consensus documents are valuable tools that assist in the decision-making process for establishing clinical strategies and optimize the delivery of health services, this consensus document has been created with the aim of developing recommendations on cretiera for hormone sensitivity and resistance in HER2-negative luminal MBC and facilitating clinical decision-making. METHODS: This consensus document was generated using a modification of the RAND/UCLA methodology, which included the definition of the project and identification of issues of interest, a non-exhaustive systematic review of the literature, an analysis and synthesis of the scientific evidence, preparation of recommendations, and external evaluation with a panel of 64 medical oncologists specializing in breast cancer. RESULTS: A Spanish panel of experts reached consensus on 32 of the 32 recommendations/conclusions presented in the first round and were accepted with an approval rate of 100% about definition of metastatic disease not susceptible to local curative treatment, definition of hormone sensitivity and hormone resistance in metastatic luminal disease and therapeutic decision-making. CONCLUSION: We have developed a consensus document with recommendations on the treatment of patients with HER2-negative luminal MBC that will help to improve therapeutic benefits.

SEOM clinical guideline for the management of immune-related adverse events in patients treated with immune checkpoint inhibitors (2019).

The use of immune checkpoint inhibitors has emerged as an effective treatment option for patients with several tumor types. By increasing the activity of the immune system, they can induce inflammatory side effects, which are often termed immune-related adverse events. These are pathophysiologically unique toxicities, compared with those from other anticancer therapies. In addition, the spectrum of the target organs is very broad. Immune-inflammatory adverse events can be life threatening. Prompt diagnosis and pharmacological intervention are instrumental to avoid progression to severe manifestations. Consequently, clinicians require new skills to successfully diagnose and manage these events. These SEOM guidelines have been developed with the consensus of ten medical oncologists. Relevant studies published in peer-review journals were used for the guideline elaboration. The Infectious Diseases Society of America grading system was used to assign levels of evidence and grades of recommendation.

SEOM clinical guidelines in gestational trophoblastic disease (2017)

Gestational trophoblastic disease (GTD) is a rare but curable disease. Recent improvements in diagnosis and molecular biology have resulted in changes in staging and treatment. These guidelines provide evidence-based recommendation on how to manage GTD (AU)

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SEOM clinical guidelines in gestational trophoblastic disease (2017).

Gestational trophoblastic disease (GTD) is a rare but curable disease. Recent improvements in diagnosis and molecular biology have resulted in changes in staging and treatment. These guidelines provide evidence-based recommendation on how to manage GTD.

Effect of growth conditions on ß-glucosidase production using Flourensia cernua leaves in a solid-state fungal bioprocess.

Flourensia cernua foliage was used in a solid-state fungal bioprocess to identify factors that could affect ß-glucosidase production such as growth medium components and partial identification of molecules from the plant material. Under an exploratory experimental design, each variable had their distinctive result on conditions, which affects and could further improve ß-glucosidase production. Under the experimental design, 1482 U/L of ß-glucosidase were detected, which marks an improvement in production compared to levels obtained in a control treatment with an activity of 1092 U/L. It was shown that inoculum, water content and pH were the factors with the greater effect on ß-glucosidase production. Polyphenolic content and cellulosic fiber in the form of raw fiber were measured to assess compound degradation of the plant material. Although fiber content was apparently unaffected, polyphenolic content decreased; ß-glucosidase was produced by A. niger GH1. This behavior could be associated with fiber level and polyphenolic content because molecules of this type can be hydrolyzed by ß-glucosidase. According to our results, F. cernua biomass can be used as a carbon source for ß-glucosidase production in a short culture time.

Ceftazidime-induced thrombocytopenia. / Trombocitopenia inducida por ceftazidima.

Ceftazidime is an antibiotic belonging to the group of third generation cephalosporins, frequently used in clinical practice for its broad antibacterial spectrum. A case report is presented on a 78-year-old man who entered the intensive care unit due to respiratory failure secondary to nosocomial pneumonia in the postoperative period of a laparoscopic hepatic bisegmentectomy for a hepatocarcinoma. It required invasive mechanical ventilation and was treated with ceftazidime, developing a progressive decrease in platelet count after the onset of this drug and after re-exposure to it, not coinciding with the introduction of other drugs. The adverse reaction was reported to the Spanish pharmacosurveillance system and according to the Naranjo algorithm the causal relationship was probable. Since no case of ceftazidime-induced thrombocytopenia was found in the literature, we consider knowledge of it relevant as an adverse effect to be taken into account given its potential severity, especially when it cannot be explained by other causes.

Tratamiento con hierro en la enfermedad renal crónica moderada-grave no terminal / Treatment with iron in non-endstage moderate-chronic kidney disease

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Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial.

BACKGROUND: Progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PROs) were significantly improved by adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) in the phase III AURELIA trial. We explored treatment outcomes according to primary platinum resistance (PPR) versus secondary platinum resistance (SPR). PATIENTS AND METHODS: Patients were categorized as PPR (disease progression <6 months after completing first-line platinum therapy) or SPR (progression ≥6 months after first platinum but <6 months after second). The exploratory Cox and logistic regression analyses correlated PFS, ORR, overall survival (OS), and PROs with the time to development of platinum resistance. RESULTS: Baseline characteristics were similar in patients with PPR (n = 262; 73%) and SPR (n = 99; 27%), although ascites were more common in the PPR subgroup. In bevacizumab-treated patients (n = 179), SPR was associated with improved PFS (median 10.2 versus 5.6 months in PPR patients; P < 0.001) and OS (median 22.2 versus 13.7 months, respectively; P < 0.001) but not PROs (22% versus 22% with improved abdominal/gastrointestinal symptoms at week 8/9). In multivariate analyses, SPR remained an independent prognostic factor for better PFS [adjusted hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25-0.67; P < 0.001] and OS (HR 0.49, 95% CI 0.30-0.80; P = 0.005) in bevacizumab-treated patients, but was not statistically significant for either end point in the chemotherapy-alone subgroup. The magnitude of PFS benefit from bevacizumab appeared greater in SPR than PPR patients (HR 0.30 versus 0.55, respectively; interaction P = 0.07) with a similar direction of effect for OS (interaction P = 0.18). CONCLUSIONS: In bevacizumab-treated patients, PFS and OS were more favorable in SPR than PPR patients with equally improved PROs. The PFS and OS benefit from combining bevacizumab with chemotherapy was more pronounced in SPR than PPR PROC. PPR versus SPR should be a stratification factor in future trials evaluating anti-angiogenic therapy for PROC.

Stability of micronutrients and phytochemicals of grapefruit jam as affected by the obtention process.

Fruits are widely revered for their micronutrient properties. They serve as a primary source of vitamins and minerals as well as of natural phytonutrients with antioxidant properties. Jam constitutes an interesting way to preserve fruit. Traditionally, this product is obtained by intense heat treatment that may cause irreversible loss of these bioactive compounds responsible for the health-related properties of fruits. In this work, different grapefruit jams obtained by conventional, osmotic dehydration (OD) without thermal treatment and/or microwave (MW) techniques were compared in terms of their vitamin, organic acid and phytochemical content and their stability through three months of storage. If compared with heating, osmotic treatments lead to a greater loss of organic acids and vitamin C during both processing and storage. MW treatments permit jam to be obtained which has a similar nutritional and functional value than that obtained when using a conventional heating method, but in a much shorter time.

Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: results of the phase II CAPRICE study.

Anthracycline and taxane-based primary chemotherapy (PCT) is the standard treatment for high-risk breast cancer (HRBC). However, conventional anthracyclines are not commonly used in elderly patients or those prone to cardiotoxicity. Pegylated liposomal doxorubicin, (PLD) has comparable efficacy, but less cardiotoxicity than conventional anthracyclines. We conducted a phase II single-arm trial to assess the efficacy and safety of PCT based on PLD followed by paclitaxel (PTX) in a HRBC population usually undertreated. Fifty patients with stage II-IIIB breast cancer and at least one risk factor for developing cardiotoxicity initiated PLD 35 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 4 weeks for four cycles, followed by 80 mg/m(2) weekly PTX for 12. Close cardiac monitoring was performed. Primary endpoint was the pathological complete response rate (pCR) in the breast. Treatment delivery and toxicities were assessed. Eighty-four per cent of patients were older than 65 years, 64 % suffered from hypertension, and 10 % had prior cardiac disease. In an intention-to-treat analysis, breast pCR was 32 % (95 % CI 19.5-46.7 %) and pCR in breast and axilla was 24 % (95 % CI 12.1-35.8 %). At diagnosis only, 26 % of patients were candidates for breast conservative surgery, which increased to 58.7 % after PCT. No significant decrease in left ventricular ejection fraction was seen. PLD followed by PTX was feasible in a fragile population of patients who were not candidates for conventional doxorubicin. Moreover, it achieved a pCR similar to standard therapy and could therefore be an option for elderly patients or cardiotoxicity-prone who present HRBC.

Volumen de dilución de fármacos intravenosos en pacientes con restricción de fluidos / Dilution volume of intravenous drugs in patients under fluid restriction therapy

Introducción: El mantenimiento del equilibrio hidroelectrolítico es esencial para el buen funcionamiento del organismo. Existen situaciones en las que se producen desequilibrios en los líquidos corporales, originando sobrecargas de fluidos, y sus consecuentes problemas asociados. Los pacientes con esta problemática, pueden beneficiarse de la administración de fármacos parenterales en el menor volumen posible. Los pacientes en estado crí- tico suelen requerir un gran número de fármacos por vía intravenosa, y altas dosis de éstos a diluir en grandes cantidades de suero. Por todo ello, parece útil buscar una estrategia de optimización de la administración de los fármacos parenterales. Objetivo: Revisar y recopilar datos referentes a volúmenes mí- nimos de dilución. Además de las vías de administración, reconstitución, diluyentes compatibles, tiempos de infusión. Método: Se incluyeron en el estudio aquellos principios activos utilizados con más frecuencia en pacientes críticos. Se realizó una búsqueda en varias fuentes de información: fichas técnicas de las especialidades farmacéuticas, Handbook on Injectable Drugs, Trissel L., American Society Healh-System Pharmacists, 15thEd., 2009, Thomson Micromedex® Healthcare series, o vía telefónica con el laboratorio fabricante del producto. Resultados: Los resultados se muestran en forma de tabla. Se revisaron 65 especialidades farmacéuticas. Conclusiones: Consideramos útil la recopilación de estos datos para optimizar la administración parenteral en pacientes críticos o que requieran una terapia restrictiva en fluidos ya que la información ha tenido que ser recopilada de distintas fuentes no encontrándose siempre en la ficha técnica. (AU)

Introduction: A fluid and electrolyte balance is essential for human health. There are some situations in which fluid imbalance occurs, causing fluid overload and consequent associated problems. Patients with these problems, may benefit from the administration of parenteral drugs in the smallest possible volume. Patients in critical condition typically require a large number of drugs intravenously, and high doses of these diluted in large quantities of serum. Therefore, it seems useful to seek an optimization strategy of parenteral drug administration. Objective: To review and collect data on minimum dilution volumes. Besides administration s routes, recons - titution, compatible diluents, infusion times. Methods: The study included those drug substances frequently used in critically ill patients. A search through multiple sources of information has been made: technical data for Propietary medicinal products, Handbook on Injectable Drugs, Trissel L., American Society Healh-System Pharmacists, 15thEd., 2009, Thomson Micromedex® Healthcare Series, or by phone calls to the manufacturers of the product. Results: Results are shown in a table. 65 drugs were revised. Conclusions: It is considered useful the collection of these data to optimize parenteral administration in critically ill patients, or in those who require restrictive fluid therapy, because information has been collected from different sources, not always found it in the technical data of the drugs (AU)