Total neoadjuvant therapy approach for the treatment of locally advanced rectal cancer. Where do we stand?

BACKGROUND: for the management of locally advanced rectal cancer (LARC), initial treatment with neoadjuvant chemoradiotherapy followed by surgery and chemotherapy in selected patients is considered one of the recommended options by the main international clinical guidelines. Nonetheless, the administration of all chemotherapy before definitive treatment (total neoadjuvant therapy or TNT) is an optimal alternative with a growing level of evidence that must be evaluated in multidisciplinary boards. This review summarizes the available data and controversies in this scenario. SUMMARY: we have analyzed the characteristics of the main published studies that assess the use of TNT in patients with LARC, evaluating their inclusion criteria and distinguishing between the employed radiotherapy fractionations, systemic agents, timing, and the implications of these treatments in regard to surgery and long-term oncological results. Our aim is to describe the evidence that supports the use of a specific regime in everyday clinical practice. KEY POINTS: there is solid evidence for the use of TNT in patients with LARC. There is no data indicating the superiority of one specific TNT scheme among all the existing options. International clinical guidelines leave the door open to choose the most adequate treatment based on the clinical and pathological characteristics of each patient. This review shows the different approaches to TNT and assesses the best options based on clinical evidence.

G4-QuadScreen: A Computational Tool for Identifying Multi-Target-Directed Anticancer Leads against G-Quadruplex DNA.

The study presents 'G4-QuadScreen', a user-friendly computational tool for identifying MTDLs against G4s. Also, it offers a few hit MTDLs based on in silico and in vitro approaches. Multi-tasking QSAR models were developed using linear discriminant analysis and random forest machine learning techniques for predicting the responses of interest (G4 interaction, G4 stabilization, G4 selectivity, and cytotoxicity) considering the variations in the experimental conditions (e.g., G4 sequences, endpoints, cell lines, buffers, and assays). A virtual screening with G4-QuadScreen and molecular docking using YASARA (AutoDock-Vina) was performed. G4 activities were confirmed via FRET melting, FID, and cell viability assays. Validation metrics demonstrated the high discriminatory power and robustness of the models (the accuracy of all models is ~>90% for the training sets and ~>80% for the external sets). The experimental evaluations showed that ten screened MTDLs have the capacity to selectively stabilize multiple G4s. Three screened MTDLs induced a strong inhibitory effect on various human cancer cell lines. This pioneering computational study serves a tool to accelerate the search for new leads against G4s, reducing false positive outcomes in the early stages of drug discovery. The G4-QuadScreen tool is accessible on the ChemoPredictionSuite website.

Interobserver Variability in Contouring Hepatocellular Carcinoma at a Tertiary Center.

BACKGROUND/AIM: The optimal imaging test for delineation of the gross tumor volume (GTV) in hepatocellular carcinoma has not been defined. The hypothesis is that magnetic resonance imaging (MRI) allows for better visualization of the extent of tumor and will optimize the accuracy of tumor delineation for liver stereotactic radiotherapy compared with computed tomography (CT) only. We evaluated the interobserver agreement in GTV of hepatocellular carcinoma in a multicenter panel and compared MRI and CT in GTV delineation. MATERIALS AND METHODS: After the institutional review boards approved the study, we analyzed anonymous CT and MRI obtained from five patients with hepatocellular carcinoma. Eight radiation oncologists at our center used CT and MRI to delineate five GTVs of liver tumors. In both CT and MRI, the GTV volumes were compared. RESULTS: The median GTV volume on MRI was 2.4 cm3 (range=0.59-15.6 cm3) compared to 3.5 cm3 (range=0.52-24.9 cm3) on CT (p=0.36). The GTV volume as defined on MRI was larger or at least as large as the GTV volume on CT in two cases. Variance and standard deviation between observers in CT and MRI were minor (6 vs. 7.87 cm3, and 2.5 vs. 2.8 cm3 respectively). CONCLUSION: In cases with well-defined tumors, CT is easier and reproducible. In cases with no defined tumor in CT, other tools are needed and MRI can be complementary. The interobserver variability in target delineation of hepatocellular carcinoma in this study is noteworthy.

MITF Downregulation Induces Death in Human Mast Cell Leukemia Cells and Impairs IgE-Dependent Degranulation.

Activating mutations in KIT (CD117) have been associated with several diseases, including gastrointestinal stromal tumors and mastocytosis. Rapidly progressing pathologies or drug resistance highlight the need for alternative treatment strategies. Previously, we reported that the adaptor molecule SH3 binding protein 2 (SH3BP2 or 3BP2) regulates KIT expression at the transcriptional level and microphthalmia-associated transcription factor (MITF) expression at the post-transcriptional level in human mast cells and gastrointestinal stromal tumor (GIST) cell lines. Lately, we have found that the SH3BP2 pathway regulates MITF through miR-1246 and miR-5100 in GIST. In this study, miR-1246 and miR-5100 were validated by qPCR in the SH3BP2-silenced human mast cell leukemia cell line (HMC-1). MiRNA overexpression reduces MITF and MITF-dependent target expression in HMC-1. The same pattern was observed after MITF silencing. In addition, MITF inhibitor ML329 treatment reduces MITF expression and affects the viability and cell cycle progression in HMC-1. We also examine whether MITF downregulation affected IgE-dependent mast cell degranulation. MiRNA overexpression, MITF silencing, and ML329 treatment reduced IgE-dependent degranulation in LAD2- and CD34+-derived mast cells. These findings suggest MITF may be a potential therapeutic target for allergic reactions and deregulated KIT mast-cell-mediated disorders.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Factors in Locally Advanced Rectal Cancer.

INTRODUCTION: The standard therapy for locally advanced rectal cancer (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) with fluoropyrimidines. There are different biomarkers used as prognostic factors in these tumors. Some studies advocate the use of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in this clinical scenario. The aim of the study was to evaluate NLR and PLR as prognostic factors of disease-free survival (DFS) and overall survival (OS) and as predictive factors of pathologic complete response (pCR) using Ryan tumor regression scoring system on surgical specimens, in patients with locally advanced rectal adenocarcinoma who received nCRT and radical surgery. METHODS: We retrospectively evaluated patients with locally advanced rectal adenocarcinoma (T3-T4, N1-N3, M0 according to the TNM classification, AJCC 8th edition) who received nCRT based on fluoropyrimidines and radical surgery. Complete blood cell count before nCRT was obtained to calculate NLR and PLR. We made subgroups of patients according to NLR and PLR. We obtained the cut-off point for these ratios based on receiver operating characteristic analysis. We analyzed OS and DFS using the Kaplan-Meier method and Cox proportional hazard models. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics, were evaluated by Pearson's χ2 or Fisher's exact test as appropriate. Multivariate analyses were performed using Cox proportional hazard regression models. RESULTS: Between February 2012 and February 2017, 100 consecutive patients were treated according to the reported schedules. Median age was 76 years (68-83). All patients received radiotherapy up to 50.4 Gy and 5-FU-based chemotherapy. 100% completed nCRT and surgery, 38% had elevated basal NLR (cut-off >1.95), and 50% had elevated basal PLR (cut-off >133). After a median follow-up of 72 months (55-88), a lower DFS was obtained in the high NLR subgroup (log-rank, Mantel-Cox 5.165, p = 0.023) and in the high PLR subgroup (log-rank, Mantel-Cox 13.971, p = 0.001). Multivariate analysis showed that PLR (p = 0.006) was a strong significant predictor of DFS. A lower OS was observed in the high NLR and PLR subgroup without significant differences (log-rank, Mantel-Cox 1.245, p = 0.265; 0.578, p = 0.447). No significant differences were obtained in any of the subgroup analysis regarding pCR rates. CONCLUSION: In light of our results, both NLR and PLR could be considered prognostic factors for DFS in patients with LARC that receive treatment with nCRT followed by surgery.

The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth.

Gastrointestinal stromal tumors (GISTs) are the most common neoplasms of mesenchymal origin, and most of them emerge due to the oncogenic activation of KIT or PDGFRA receptors. Despite their relevance in GIST oncogenesis, critical intermediates mediating the KIT/PDGFRA transforming program remain mostly unknown. Previously, we found that the adaptor molecule SH3BP2 was involved in GIST cell survival, likely due to the co-regulation of the expression of KIT and Microphthalmia-associated transcription factor (MITF). Remarkably, MITF reconstitution restored KIT expression levels in SH3BP2 silenced cells and restored cell viability. This study aimed to analyze MITF as a novel driver of KIT transforming program in GIST. Firstly, MITF isoforms were characterized in GIST cell lines and GIST patients' samples. MITF silencing decreases cell viability and increases apoptosis in GIST cell lines irrespective of the type of KIT primary or secondary mutation. Additionally, MITF silencing leads to cell cycle arrest and impaired tumor growth in vivo. Interestingly, MITF silencing also affects ETV1 expression, a linage survival factor in GIST that promotes tumorigenesis and is directly regulated by KIT signaling. Altogether, these results point to MITF as a key target of KIT/PDGFRA oncogenic signaling for GIST survival and tumor growth.

SARS-CoV-2 Virus in Cancer Patients: A New Unknown in an Unsolved Equation.

INTRODUCTION: Cancer patients are more susceptible to infections, and infection can be more severe than in patients without cancer diagnosis. We conducted this retrospective study in patients admitted for SARS-CoV-2 infection in order to find differences in inflammatory markers and mortality in cancer patients compared to others. METHODS: We reviewed the electronic records of patients admitted for SARS-CoV-2 infection confirmed by PCR from March to September 2020. Data on socio-demographics, comorbidities, inflammatory makers, and cancer-related features were analyzed. RESULTS: 2,772 patients were admitted for SARS-CoV-2, to the Hospital Universitario Ramón y Cajal in Madrid during this period. Of these, 2,527 (91%) had no history of neoplastic disease, 164 (5.9%) patients had a prior history of cancer but were not undergoing oncological treatment at the time of infection, and 81 (2.9%) were in active treatment. Mortality in patients without a history of cancer was 19.5%, 28.6% for patients with a prior history of cancer, and 34% in patients with active cancer treatment. Patients in active oncology treatment with the highest mortality rate were those diagnosed with lung cancer (OR 5.6 95% CI: 2.2-14.1). In the multivariate study, active oncological treatment (OR 2.259 95% CI: 1.35-3.77) and chemotherapy treatment (OR 3.624 95% CI: 1.17-11.17), were statistically significant factors for the risk of death for the whole group and for the group with active oncological treatment, respectively. CONCLUSION: Cancer patients on active systemic treatment have an increased risk of mortality after SARS-CoV-2 infection, especially with lung cancer or chemotherapy treatment.

SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain of function in receptor tyrosine kinases type III, KIT, or PDGFRA drives the majority of GIST. Previously, our group reported that silencing of the adaptor molecule SH3 Binding Protein 2 (SH3BP2) downregulated KIT and PDGFRA and microphthalmia-associated transcription factor (MITF) levels and reduced tumor growth. This study shows that SH3BP2 silencing also decreases levels of ETV1, a required factor for GIST growth. To dissect the SH3BP2 pathway in GIST cells, we performed a miRNA array in SH3BP2-silenced GIST cell lines. Among the most up-regulated miRNAs, we found miR-1246 and miR-5100 to be predicted to target MITF and ETV1. Overexpression of these miRNAs led to a decrease in MITF and ETV1 levels. In this context, cell viability and cell cycle progression were affected, and a reduction in BCL2 and CDK2 was observed. Interestingly, overexpression of MITF enhanced cell proliferation and significantly rescued the viability of miRNA-transduced cells. Altogether, the KIT-SH3BP2-MITF/ETV1 pathway deserves to be considered in GIST cell survival and proliferation.

Brain metastases from non-small cell lung carcinoma: an overview of classical and novel treatment strategies.

Background: The development of brain metastases is a common problem in patients diagnosed with non-small cell lung carcinoma (NSCLC). Technological advances in surgery and radiotherapy have allowed greater local control. Moreover, the emergence of targeted therapies and immunotherapy with greater activity on the central nervous system than classical chemotherapy have given way to new strategies in the treatment of brain metastases. We review the current role of local treatments, surgery and radiotherapy, and the most effective combination strategies with the new systemic treatments. Relevance for patients: Brain metastases frequently occur during the course of NSCLC. In recent years, a range of treatments have appeared, such as targeted treatments or immunotherapy, with greater activity at the brain level than classical chemotherapy. Radiotherapy treatment is also now much more conformal and ablative doses can be delivered to the volume of the metastatic area, providing greater local control and less neurological toxicity. However, surgery is still required in cases where anatomopathological specimens are needed and when compressive effects appear. An important challenge is how to combine these treatments to achieve the best control and minimise patients' neurological impairments, especially because of limited experience with the new target drugs, and the unknown toxicity of the different combinations. Future research should therefore focus on these areas in order to establish the best strategies for the treatment of brain metastases from non-small cell lung cancer. Core tips: In this work, we intend to elucidate the best therapeutic options for patients diagnosed with brain metastases of NSCL, which include: surgery, WBRT, radiosurgery or systemic treatment, and the most effective combinations and timings of them, and the ones with the lowest associated toxicity.

Dose-escalated neoadjuvant chemoradiotherapy for locally advanced oesophageal or oesophagogastric junctional adenocarcinoma.

Background: Neoadjuvant chemoradiotherapy with CROSS-protocol is the standard of care for locally advanced esophageal cancer. The purpose of this study was to demonstrate an improvement in complete pathological response (ypCR) after a dose-escalation neoadjuvant protocol compared to standard treatment. Secondary endpoints were disease-free survival (DFS) and acute gastrointestinal toxicity. Material and methods: We prospectively evaluated patients with locally advanced esophageal adenocarcinoma who received neoadjuvant chemoradiotherapy. The radiation dose was 41.4 Gy in 23 fractions or 50.4 Gy in 28 fractions with weekly administration of six intravenous cycles of carboplatin AUC 2 mg/mL and intravenous paclitaxel 50 mg/m2 followed by surgery. Results: Between December 2015 and July 2020, 21 patients were treated according to the reported radiation schedules. Median age was 61 years (57-67). 20 (95.2%) tumors were located at the esophagogastric junction and 1 (4.8%) in the middle esophagus. Five (23.8%) were stage II and 16 (76.2%) stage III. Twelve (57.1%) patients received 41.4 Gy (standard group) and 9 (42.9%) received 50.4 Gy (intensification group), with 5 (41.67%) and 5 (55.6%) presenting ypCR in the standard and intensification group, respectively (p = 0.67). After a median follow-up of 17 months (8-30), DFS in the standard group was 17.78 months [95% (CI, confidence interval): 12.9-22.6] and 45.5 months (95% CI: 24.4-66.05) in the intensification group (p = 0.299). Grade III acute gastrointestinal toxicity was 16% and 33.33%, respectively (p = 0.552). Postoperative toxicity events ≥ Grade III were 5 (41.7%) and 4 (44.4%), respectively (p = 0.623). Conclusions: In our study we found a trend towards a higher complete pathological response-rate and disease-free survival in the intensification group compared to the standard group, with no differences in gastrointestinal toxicity. Well-designed randomized and controlled trials are needed to obtain conclusive data.

Muerte súbita inesperada en epilepsia. Revisión sobre la implicación del tallo encefálico / Sudden unexpected death in epilepsy. Review about the brainstem involvement

RESUMEN La muerte súbita inesperada en epilepsia, se define como la muerte repentina -presenciada o no- de personas con epilepsia, no traumática ni por ahogamiento, con o sin evidencias de crisis, y en quienes el examen postmorten no revela una causa estructural o toxicológica de muerte. El objetivo de esta revisión es describir las evidencias más recientes, publicadas en la literatura, sobre la participación crucial del tallo encefálico en la fisiopatología de la muerte súbita inesperada en epilepsia. Se realizó una búsqueda bibliográfica en la base de datos computarizada PubMed. Los estudios en modelos animales han demostrado que los mecanismos de la muerte súbita inesperada en epilepsia involucran un primer evento mediado por una crisis, seguido por la despolarización cortical, que se propaga al tallo encefálico y que resulta en una disfunción autonómica causante de apnea central, edema pulmonar o arritmia cardiaca. Los estudios en humanos se han apoyado en las imágenes de resonancia magnética para evaluar el papel de diferentes áreas del tallo encefálico en la muerte súbita inesperada en epilepsia. Las evidencias acumuladas por la literatura, tanto en estudios con animales como humanos, evidencian el papel fundamental desempeñado por las estructuras del tallo encefálico en la fisiopatología de la muerte súbita inesperada en epilepsia.

ABSTRACT Sudden unexpected death in epilepsy is defined as the sudden death-whether witnessed or not-of people with epilepsy, not traumatic or due to drowning, with or without evidence of seizures, and in whom postmortem examination does not reveal a structural or toxicological cause of death. The aim of this review is to describe the most recent evidence published in the literature, on the crucial involvement of the brain stem in the pathophysiology of sudden unexpected death in epilepsy. A bibliographic search was conducted in PubMed computerized database. Studies in animal models have shown that the mechanisms of sudden unexpected death in epilepsy involve a first seizure-mediated event, followed by cortical depolarization, which spreads to the brainstem and results in autonomic dysfunction causing central apnea, pulmonary edema or cardiac arrhythmia. Studies in humans have relied on magnetic resonance imaging to assess the role of the brainstem in sudden unexpected death in epilepsy. The evidence accumulated in the literature, both in animal and in human studies, shows the role played by brainstem structures in the pathophysiology of sudden unexpected death in epilepsy.

Current treatment landscape for oligometastatic non-small cell lung cancer.

The management of patients with advanced non-small cell lung carcinoma (NSCLC) has undergone major changes in recent years. On the one hand, improved sensitivity of diagnostic tests, both radiological and endoscopic, has altered the way patients are staged. On the other hand, the arrival of new drugs with antitumoral activity, such as targeted therapies or immunotherapy, has changed the prognosis of patients, improving disease control and prolonging survival. Finally, the development of radiotherapy and surgical and interventional radiology techniques means that radical ablative treatments can be performed on metastases in any location in the body. All of these advances have impacted the treatment of patients with advanced lung cancer, especially in a subgroup of these patients in which all of these treatment modalities converge. This poses a challenge for physicians who must decide upon the best treatment strategy for each patient, without solid evidence for one optimal mode of treatment in this patient population. The aim of this article is to review, from a practical and multidisciplinary perspective, published evidence on the management of oligometastatic NSCLC patients. We evaluate the different alternatives for radical ablative treatments, the role of primary tumor resection or radiation, the impact of systemic treatments, and the therapeutic sequence. In short, the present document aims to provide clinicians with a practical guide for the treatment of oligometastatic patients in routine clinical practice.

Relationship between nutritional treatment compliance and nutritional status improvements in patients with gastrointestinal impairment taking an oral peptide-based supplement.

OBJECTIVES: Compliance in outpatients with gastrointestinal (GI) malabsorption is key in nutritional treatment. The objective of this study was to assess compliance in patients with GI impairment and malnutrition taking a high-calorie, high-protein, peptide-based oral nutritional supplement (ONS-PBD). METHODS: A prospective, multicenter, observational study was conducted in 19 medical sites in Spain where ONS-PBD were prescribed as standard of care. Patients consumed ONS-PBD daily for 12 wk. Compliance was calculated as the percentage consumed of the prescribed amount of ONS per day. RESULTS: A total of 90 adult patients were included in the study, of whom 64 completed the 12-wk regimine. Mean compliance was 78.8% ± 24.5%. Risk of malnutrition decreased in 56.3% of patients at 12 wk, as measured with the malnutrition universal screening tool. A reduction in abdominal pain was observed and stool consistency improved, with a mean of 54.7% and 27.5%, respectively. Improvements in quality of life and a decrease in percentage of patients with severe functional impairment were observed. CONCLUSIONS: These data show that ONS-PBD compliance in malnourished patients with GI symptoms is high, reducing GI symptoms and improving patients' nutritional status.

Uncovering the Mast Cell Response to Mycobacterium tuberculosis.

The immunologic mechanisms that contribute to the response to Mycobacterium tuberculosis infection still represent a challenge in the clinical management and scientific understanding of tuberculosis disease. In this scenario, the role of the different cells involved in the host response, either in terms of innate or adaptive immunity, remains key for defeating this disease. Among this coordinated cell response, mast cells remain key for defeating tuberculosis infection and disease. Together with its effector's molecules, membrane receptors as well as its anatomical locations, mast cells play a crucial role in the establishment and perpetuation of the inflammatory response that leads to the generation of the granuloma during tuberculosis. This review highlights the current evidences that support the notion of mast cells as key link to reinforce the advancements in tuberculosis diagnosis, disease progression, and novel therapeutic strategies. Special focus on mast cells capacity for the modulation of the inflammatory response among patients suffering multidrug resistant tuberculosis or in co-infections such as current COVID-19 pandemic.

[Adequacy of pre-surgical hand hygiene in an university teaching hospital in Madrid (Spain).] / Adecuación de la higiene prequirúrgica de manos en un hospital universitario de Madrid.

OBJECTIVE: We know the importance of hand hygiene in the prevention of healthcare-associated infections. However, its compliance is still a challenge. Moreover, when it is complied with, as in the case of preoperative hygiene, there are few studies on the proper performance of the technique. The aim of this paper is to assess adequacy of pre-surgical hand hygiene in operating room staff of different surgical specialities at a university teaching hospital in Madrid. METHODS: A cross-sectional study was made. Adequacy of pre-surgical hand hygiene was assessed in operating room staff of the different specialities and professional categories by direct covert observation. It was evaluated in 852 opportunities during the months of October, November and December 2020. A specific form was designed for data collection, following the recommendations of the World Health Organisation (WHO). Adequacy was described with frequency distributions of the different groups observed. Whether Chi-square or Fisher's exact tests were used to compare the different categories. RESULTS: Pre-surgical hand hygiene opportunities were evaluated, 75.5% in surgeons and 24.5% in nurses. Overall compliance with pre-surgical hand hygiene technique was 80.5 % (686). The most frequent surgical service evaluated was General Surgery with 240 observations. The professional category with the best adequacy was nursing (86.1%) and the surgical service one was Traumatology (90.2%). An stopwatch was used by some 25.8% of the evaluated professionals, with an adequate hygiene time of 96,8% (p<0,05) for that group. CONCLUSIONS: The overall adequacy of pre-surgical hand hygiene in the operating room professionals is high. Significant statistically differences in adequacy are found between professional categories and surgical specialities, with better compliance in nursing staff and in Traumatology. Better results are achieved by the use of an stopwatch.

OBJETIVO: Sabemos la importancia que tiene la higiene de manos en la prevención de infecciones asociadas a la asistencia sanitaria. Sin embargo, a día de hoy, su cumplimiento, es un reto. Además, cuando se cumple, como es el caso de en la higiene prequirúrgica, pocos estudios hay sobre la adecuada realización de la técnica. El objetivo de este estudio fue evaluar la adecuación de la higiene de manos prequirúrgica en profesionales de quirófano de un Hospital Universitario de Madrid. METODOS: Se realizó un estudio descriptivo trasversal. Se evaluó la adecuación de la higiene de manos prequirúrgica mediante observación directa y enmascarada en 852 oportunidades durante los meses de octubre, noviembre y diciembre de 2020. Se consideró adecuada la higiene de manos si ésta se realizaba según la técnica correcta y durante el tiempo indicado. La adecuación de la higiene de manos se describió con la distribución de frecuencias y las diferencias entre categorías se compararon con la prueba x2 de Pearson o prueba exacta de Fisher. RESULTADOS: Se evaluaron las oportunidades de higiene de manos prequirúrgica, el 75,5% en cirujanos y el 24,5% en personal de enfermería. La adecuación global de la higiene de manos fue del 80,5%. La categoría profesional con mejor adecuación fue Enfermería (86,1%) (p<0,05) y el servicio quirúrgico con mejor adecuación fue Traumatología (90,2%) (p<0,05). Un 25,8% de los profesionales evaluados utilizó el apoyo del cronómetro, consiguiendo este grupo una adecuación al tiempo de higiene del 96,8% (p<0,05). CONCLUSIONES: La adecuación global de la higiene de manos prequirúrgica en nuestros profesionales es muy alta. Se encuentran diferencias estadísticamente significativas de cumplimiento entre categorías profesionales y especialidades quirúrgicas, siendo mejor la adecuación en el personal de Enfermería y en la especialidad de Traumatología. El apoyo del cronómetro consigue mejores resultados en la adecuación al tiempo de higiene.

Microbiological aspects of osteomyelitis in veterinary medicine: drawing parallels to the infection in human medicine.

Osteomyelitis is a challenging infectious disease affecting humans and animals. It is difficult to diagnose because, in many cases, symptoms are non-specific and, for example in implant-related cases, can appear long time after surgery. In addition to this, it is also difficult to treat due to the need to find the appropriate antibiotic regime and delivery system to reach the site of infection and to avoid development of bacterial resistance. The central purpose of this review is to compare the microbiological aspects of osteomyelitis in human and veterinary medicine, with the aim of improving the microbiological diagnosis and treatment of this infection in animals. Furthermore, the study of osteomyelitis in animals may help to improve the development of animal models for testing new treatments in humans. Host factors and underlying conditions have been studied mainly in humans, although aspects as immunodeficiency have been described in some veterinary cases. Even when Staphylococcus aureus is still considered the most prevalent causing microorganism, this prevalence should be reviewed using molecular diagnostic techniques, and this could affect treatment options. New approaches to treatment include local delivery of antibiotics using different biomaterials, antimicrobial photodynamic therapy, and new antimicrobial compounds. We would like to remark the need of large, high-quality clinical trials and of the development of guides for the diagnosis and treatment of osteomyelitis in different animal species.

Management of Resectable Stage III-N2 Non-Small-Cell Lung Cancer (NSCLC) in the Age of Immunotherapy.

Stage III non-small-cell lung cancer (NSCLC) with N2 lymph node involvement is a heterogeneous group with different potential therapeutic approaches. Patients with potentially resectable III-N2 NSCLC are those who are considered to be able to receive a multimodality treatment that includes tumour resection after neoadjuvant therapy. Current treatment for these patients is based on neoadjuvant chemotherapy +/- radiotherapy followed by surgery and subsequent assessment for adjuvant chemotherapy and/or radiotherapy. In addition, some selected III-N2 patients could receive upfront surgery or pathologic N2 incidental involvement can be found a posteriori during analysis of the surgical specimen. The standard treatment for these patients is adjuvant chemotherapy and evaluation for complementary radiotherapy. Despite being a locally advanced stage, the cure rate for these patients continues to be low, with a broad improvement margin. The most immediate hope for improving survival data and curing these patients relies on integrating immunotherapy into perioperative treatment. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors is already a standard treatment in stage III unresectable and advanced NSCLC. Data from the first phase II studies in monotherapy neoadjuvant therapy and, in particular, in combination with chemotherapy, are highly promising, with impressive improved and complete pathological response rates. Despite the lack of confirmatory data from phase III trials and long-term survival data, and in spite of various unresolved questions, immunotherapy will soon be incorporated into the armamentarium for treating stage III-N2 NSCLC. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy.