Documento de consenso sobre tabaquismo y riesgo vascular.

Consensus statement on smoking and vascular risk About 22% of the Spanish population are daily smokers. Men are more likely to smoke than women. In Spain, women between 15-25 years of age smoke as much or more than men. Every smoker should be assessed for: physical dependence on nicotine (Fagerström test), social and psychological dependence (Glover Nilsson test), level of motivation to quit (Richmond test), probability of therapy success (Henri-Mondor and Michael-Fiore tests), and stage of behavioral change development (Prochaska and DiClementi). Advice on smoking cessation is highly cost-effective and should always be provided. Smoking is an enhancer of cardiovascular risk because it acts as a pathogen agent in the development of arteriosclerosis and is associated with ischemic heart disease, stroke, and peripheral artery disease. Smoking increases the risk of chronic lung diseases (COPD) and is related to cancers of the lung, female genitalia, larynx, oropharynx, bladder, mouth, esophagus, liver and biliary tract, and stomach, among others. Combined oral contraceptives should be avoided in women smokers older than 35 years of age due to the risk of thromboembolism. In smoking cessation, the involvement of physicians, nurses, psychologists, etc. is important, and their multidisciplinary collaboration is needed. Effective pharmacological treatments for smoking cessation are available. Combined treatments are recommended when smoker's dependence is high. For individuals who are unable to quit smoking, a strategy based on tobacco damage management with a total switch to smokeless products could be a less dangerous alternative for their health than continuing to smoke.

Angina de Ludwig, aspectos semiológicos útiles para el diagnóstico presuntivo de una patología letal / Ludwig`s angina, useful semiologic points for the presumptive diagnosis of a lethal pathology

Resumen Mujer de 74 años consulta al servicio de urgencia por cuadro de sepsis origen aparentemente no precisado, hasta su evaluación por dermatología que describe eritema violáceo cervical anterior más una infección en cavidad bucal como puerta de entrada. Considerando la clínica y los estudios por imágenes confirmamos el diagnóstico de Angina de Ludwig, cuadro de alta morbimortalidad que puede progresar a otras complicaciones más graves. Finalmente la paciente evoluciona de manera tórpida no respondiendo a medidas realizadas de soporte y fallece. La Angina de Ludwig es una celulitis de evolución rápida y grave, muy poco frecuente, que por lo general tiene una puerta de entrada a través de infecciones de la mucosa oral, donde su sospecha obliga a iniciar terapia precoz con antibióticos, quirúrgico y soporte.

Abstract This is a 74-year-old female patient with comorbidities who consulted the emergency service due to symptoms of sepsis of apparently unspecified origin, until her evaluation by dermatology revealed mild anterior cervical violaceous erythema and probable dental infection as the portal of entry. Based on clinical and imaging findings, a diagnosis of Ludwig's angina is confirmed, a condition with high morbidity and mortality that can progress to other more severe complications. Finally, the patient had a torpid evolution, not responding to support measures, and died. Ludwig's Angina is a cellulitis of etiology, usually rapidly progressive, infrequent oral infections, where a mandatory physical examination should be considered and suspected in order to start early therapy.

Broad bandwidth air-coupled micromachined ultrasonic transducers for gas sensing.

The present work aims to develop ultra-wide bandwidth air-coupled capacitive micromachined ultrasonic transducers (CMUTs) for binary gas mixture analysis. The detection principle is based on time-of-flight (ToF) measurements, in order to monitor gas ultrasound velocity variations. To perform such measurements, CMUTs were especially designed to work out of resonance mode, like a microphone. The chosen membrane size is 32 × 32 µm2 and gap height is 250 nm. The resonance frequency and collapse voltage were found at 8 MHz and 58 V respectively. As mentioned, the CMUTs were exploited in quasi-static operating mode, in a very low frequency band, from 1 MHz to 1.5 MHz frequencies. The transducer impulse response was characterised, and a -6 dB relative fractional frequency bandwidth (FBW) higher than 100% was measured, enabling to use CMUT for the targeted application. Additionally, a measuring cell has been designed to hold the fabricated CMUT emitter and receiver prototypes facing each other. The volume inside the cell was kept lower than 3 mL and the surface of emitter/receiver was 1.6 × 8 mm2. To validate the general principle of the proposed technique, two binary gas mixtures of CO2/N2 and H2/N2, with varying concentrations, have been tested. The results are very promising with a measured limit of detection (LOD) of 0.3% for CO2 in N2 and 0.15% for H2 in N2.

SEOM clinical guidelines for the treatment of head and neck cancer (2020).

Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m2 in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease.

Long-term outcomes of induction chemotherapy followed by chemoradiotherapy vs chemoradiotherapy alone as treatment of unresectable head and neck cancer: follow-up of the Spanish Head and Neck Cancer Group (TTCC) 2503 Trial.

BACKGROUND: Our previous phase-3 study (TTCC 2503) failed to show overall survival advantage of 2 induction chemotherapy (IC) regimens followed by standard concurrent chemoradiotherapy (CRT) over CRT alone in patients with unresectable locally advanced head and neck squamous-cell carcinoma (LAHNSCC). This study described the long-term survival of those patients. MATERIALS AND METHODS: Long-term follow-up study of patients with untreated LAHNSCC assigned to IC (three cycles), with either docetaxel, cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CRT, or CRT alone, included in the previous TTCC 2503 trial. RESULTS: In the intention-to-treat population (n = 439), the median OS times were 25.4 (95% CI, 16.8-34.4), 26.2 (95% CI, 18.2-36.6) and 25.4 months (95% CI, 17.4-36.0) in the TPF-CRT, PF-CRT and CRT arms, respectively (log-rank p = 0.51). In the per-protocol population (n = 355), patients with larynx-hypopharynx primary tumors treated with IC (TPF or PF) followed by CRT had a longer median PFS than those who received CRT alone. Moreover, patients with ECOG 0 treated with IC (TPF or PF) followed by CRT had a better TTF than those with CRT alone. There were no statistically significant differences in terms of OS, PFS or TTF, according to the tumor load or affected nodes. CONCLUSION: After a long follow-up, the TTCC 2503 trial failed to show the benefit of IC-CRT in unresectable LAHNSCC regarding the primary end point. However, fit patients with ECOG 0 and primary larynx-hypopharyngeal tumors may benefit from the use of IC if administered by an experienced team. ClinicalTrials.gov identifier NCT00261703.

A new scenario in metastatic renal cell carcinoma: a SOG-GU consensus.

BACKGROUND: This article describes and compares approved targeted therapies and the newer immunotherapy agents. MATERIALS AND METHODS: This article especially performs an in-depth review of currently available data for tivozanib, explaining its mechanism of action, its safety profile and its role as an efficacy drug in the management of renal cancer. RESULTS: Despite the fact that the treatment of advanced RCC has been dramatically modified in recent years, durable remissions are scarce and it remains a lethal disease. For first- and second-line therapy, there is now growing evidence to guide the selection of the appropriate treatment. CONCLUSIONS: Several TKIs are standard of care at different settings. Among those approved TKIs, tivozanib has similar efficacy than others with a better safety profile. The use of prognostic factors is critical to the selection of optimal therapy.

SEOM clinical guideline thyroid cancer (2019).

Thyroid carcinoma is the most frequent endocrine malignancy and accounts for around 3% of global cancer incidence. Different histologies and clinical scenarios make necessary a multidisciplinary approach that includes new diagnostic methods and surgical, radiopharmaceutical and systemic therapies. This guideline updates several aspects of management of thyroid cancer.

Evolutionary aspects on the origin, distribution and ramifications of the ischiadicus nerve in the giant anteater (Myrmecophaga tridactyla) / Aspectos evolutivos sobre as origens, distribuições e ramificações dos nervos isquiáticos do tamanduá-bandeira (Myrmecophaga tridactyla)

This work aimed to describe the origin, distribution, and ramifications of the ischiadicus nerve in the giant anteater and to provide anatomical data which could explain not only the evolutionary aspects but also provide important information for other related works. For the present study, four specimens were used, prepared by perfusion of 10% formaldehyde solution via the femoral artery, for conservation and dissection. The origin of the right and left ischiadicus nerves in the giant anteater from the ventral ramification of the third lumbar (L3) and the first (S1), second (S2), and third (S3) sacral spinal nerves. These nerves were symmetrical in all animals studied. The distribution and ramification occurred to the superficial, middle, and deep gluteal, gemelli, piriform, quadratus femoris, tensor fasciae latae, caudal crural abductor, cranial and caudal parts of the biceps femoris, adductor, semitendinous, and cranial and caudal parts of the semimembranous muscles. Based on the origins of the ischiadicus nerves, there is a caudal migration in the nerve location in animals in a more recent position on the evolutionary scale due to reconfiguration of the lumbosacral plexus, resulting from the increase in a number of lumbar vertebrae. There is no complete homology of the muscle innervation.(AU)

Objetivou-se descrever as origens, distribuições e ramificações dos nervos isquiáticos no tamanduá-bandeira, disponibilizando, assim, dados anatômicos que possam não só elucidar os aspectos evolutivos como também fornecer informações importantes para áreas afins. Foram utilizados quatro espécimes preparados por meio da perfusão de formaldeído 10% via artéria femoral, para conservação e dissecação. As origens dos nervos isquiáticos direito e esquerdo no tamanduá-bandeira foram provenientes dos ramos ventrais dos nervos espinhais lombares três e sacrais um, dois e três, sendo simétricos em todos os animais estudados. As distribuições e ramificações ocorreram nos músculos glúteos superficial, médio e profundo; gêmeo; piriforme; quadrado femoral; tensor da fáscia lata; abdutor crural caudal; bíceps femoral parte cranial; bíceps femoral parte caudal; adutor; semitendíneo; semimembranáceo parte cranial e semimembranáceo parte caudal. Notou-se que houve uma migração caudal na localização deste nervo nos animais mais recentes na escala evolutiva, devido a uma reconfiguração do plexo lombossacral decorrente do aumento no número de vértebras lombares, não havendo uma homologia total quanto à inervação dos músculos.(AU)

[Incidence, trend and municipal distribution of tobacco-associated tumours in the Health Area of León: 1997-2014]. / Incidencia, tendencia y distribución municipal de los tumores asociados al tabaco en el Área de Salud de León: 1997-2014.

OBJECTIVE: For cancer incidence, tobacco use is one of the main avoidable risk factors.The aim of this study is to describe the frequency, trend and geographical distribution of the incidence of tobacco-associated tumours in the León Health Area, Spain. MATERIAL AND METHODS: An observational, descriptive study was carried out on tumours of Hospital Registry of Tumours of the University Hospital Complex of León between 1997 and 2014. León Health Area residents, associated with smoking were included. Gross and adjusted rates were calculated and adjusted for triennials. For the analysis of spatial distribution, municipal relative hazards were smoothed by adjusting the Besag, York, and Mollié model and for their posterior probabilities for relative hazards to be higher than 1, using Bayesian methods. RESULTS: A total of 7,103 cases were included. Crude incidence rates rose from 116.4 (1997-1999) to 228.0 (2012-2014) per 100,000 men, and from 19.8 (1997-1999) to 44.5 (2012-2014) per 100,000 women. The adjusted rates for the European population also increased from 116.2 (1997-1999) to 136.9 (2012-2014) per 100,000 men, and from 11 (1997-1999) to 24.5 (2012-2014) per 100,000 women. In the south and centre of the province, there were municipalities with high relative hazards, several of them higher than 2 with posterior probabilities of 1. CONCLUSIONS: Tumours associated with tobacco increased in the triennial studied, especially in women. The different geographical distribution can be used as a tool to prevent tobacco consumption in the areas involved.

2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary.

Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.

CMV viral load in bronchoalveolar lavage for diagnosis of pneumonia in allogeneic hematopoietic stem cell transplantation.

The objective of this report is to analyze the value of CMV viral load (VL) in bronchoalveolar lavage (BAL) in recipients of allogeneic hematopoietic stem cell transplantation (AHSCT) and to analyze the concordance between CMV quantification in plasma and BAL samples. Fifty-six patients were included; in 16 (28.6%) patients with symptoms of lung disease a BAL sample was collected, 7 (43.7%) patients had a VL >150 copies/mL (six had probable CMV pneumonia). Patients with CMV pneumonia were female (100%), of median age 53.5 years, and the median time from transplantion to onset of symptoms was 67.5 days. Pneumonia was early in three cases (incidence 5.4%). Median BAL VL was 53 250 copies/mL and plasma VL was 538 copies/mL (in one patient, the plasma VL was negative). Three (50.0%) patients had an improvement in the first week of treatment, and plasma VL became negative; the other 3 (50.0%) patients died with a CMV pneumonia refractory to treatment. Therefore, any value of CMV VL in BAL, especially if it is greater than plasma, with compatible signs or symptoms, should be considered suggestive of CMV pneumonia in recipients of AHSCT and they should receive specific treatment.

Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part).

BACKGROUND: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvß5 integrin. Cilengitide selectively inhibits αvß3 and αvß5 integrins and is investigated as a treatment strategy. PATIENTS AND METHODS: The phase I/II study ADVANTAGE evaluated cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M-SCCHN. The phase II part reported here was an open-label, randomized, controlled trial investigating progression-free survival (PFS). Patients received up to six cycles of PFE alone or combined with cilengitide 2000 mg once (CIL1W) or twice (CIL2W) weekly. Thereafter, patients received maintenance therapy (cilengitide arms: cilengitide plus cetuximab; PFE-alone arm: cetuximab only) until disease progression or unacceptable toxicity. RESULTS: One hundred and eighty-two patients were treated. Median PFS per investigator read was similar for CIL1W + PFE, CIL2W + PFE, and PFE alone (6.4, 5.6, and 5.7 months, respectively). Accordingly, median overall survival and objective response rates were not improved with cilengitide (12.4 months/47%, 10.6 months/27%, and 11.6 months/36%, respectively). No clinically meaningful safety differences were observed between groups. None of the tested biomarkers (expression of integrins, CD31, Ki-67, vascular endothelial growth factor receptor 2, vascular endothelial-cadherin, type IV collagen, epidermal growth factor receptor, or p16 for human papillomavirus) were predictive of outcome. CONCLUSION: Neither of the cilengitide-containing regimens demonstrated a PFS benefit over PFE alone in R/M-SCCHN patients.

Invasive device-related infections after heart surgery.

OBJECTIVE: To analyze postoperative infections in critically ill patients undergoing heart surgery. SETTING: Intensive care units (ICUs). DESIGN: An observational, prospective, multicenter study was carried out. PATIENTS: Patients in the postoperative period of heart surgery admitted to the ICU and included in the ENVIN-HELICS registry between 2005 and 2011. MAIN OUTCOME VARIABLES: Mechanical ventilation associated pneumonia (MVP), urinary catheter-related infection (UCI), primary bacteremia (PB), PB related to vascular catheters (PB-VC) and secondary bacteremia. RESULTS: Of a total of 97,692 patients included in the study, 9089 (9.3%) had undergone heart surgery. In 440 patients (4.8%), one or more infections were recorded. Infection rates were 9.94 episodes of MVP per 1000 days of mechanical ventilation, 3.4 episodes of UCI per 1000 days of urinary catheterization, 3.10 episodes of BP-VC per 1000 days of central venous catheter, and 1.84 episodes of secondary bacteremia per 1000 days of ICU stay. Statistically significant risk factors for infection were ICU stay (odds ratio [OR] 1.18, 95%CI 1.16-1.20), APACHE II upon admission to the ICU (OR 1.05, 95%CI 1.03-1.07), emergency surgery (OR 1.67, 95%CI 1.13-2.47), previous antibiotic treatment (OR 1.38, 95%CI 1.04-1.83), and previous colonization by Pseudomonas aeruginosa (OR 18.25, 95%CI 3.74-89.06) or extended spectrum beta-lactamase producing enterobacteria (OR 16.97, 95%CI 5.4-53.2). The overall ICU mortality rate was 4.1% (32.2% in patients who developed one or more infections and 2.9% in uninfected patients) (P < .001). CONCLUSIONS: Of the patients included in the ENVIN-HELICS registry, 9.3% were postoperative heart surgery patients. The overall mortality was low but increased significantly in patients who developed one or more infection episodes.

Calprotectin: a novel biomarker for the diagnosis of pleural effusion.

BACKGROUND: Novel non-invasive biomarkers for the precise diagnosis of malignancy in pleural effusion (PE) are needed. The aim of this study was to determine the diagnostic accuracy of calprotectin for predicting malignancy in patients with exudative PE. METHODS: Calprotectin concentration was measured in 156 individuals diagnosed with exudative PE (67 malignant and 89 benign). Calprotectin accuracy for discriminating between malignant and benign PE was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate logistic regression were performed to test the association between calprotectin levels and malignant PE. RESULTS: Calprotectin levels were significantly lower in malignant pleural fluid (257.2 ng ml(-1), range: 90.7-736.4) than benign effusions (2627.1 ng ml(-1), range: 21-9530.1). The area under the curve was 0.963. A cutoff point of ≤ 736.4 ng ml(-1) rendered a sensitivity of 100%, with a specificity of 83.15%, which could prove useful to delimit those patients with negative cytology tests that should be referred for more invasive diagnostic procedures. Logistic regression demonstrated a strong association between calprotectin and malignancy (adjusted OR 663.14). CONCLUSION: Calprotectin predicts malignancy in pleural fluid with high accuracy and could be a good complement to cytological methods.