Profound ctDNA and radiological responses after 2 cycles of avelumab in a metastatic Merkel cell carcinoma of the head and neck.

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon skin cancer that in more than 90 % of cases develops within the head and neck region. MCC is an aggressive disease with a dismal prognosis before the advent of immunotherapy. Avelumab, an anti-PDL1 agent is approved since 2017 for the treatment of advanced MCC after demonstrating a high response rate and favorable impact in survival. METHODS: Next generation sequencing (NGS) of the primary tumor biopsy from initial diagnosis (Foundation One CDx, Roche Diagnostics) as well as from plasma samples (Foundation One Liquid, Roche Diagnostics) obtained before and during treatment with avelumab were performed. RESULTS: We present the case of a patient with a metastatic MCC developing in the left parotid gland / pre-auricular area in an 80-year-old male with a long-lasting history of high UV exposure. After two cycles of avelumab 10 mg/kg/q2wk a near complete metabolic response and a major radiological response occurred in parallel to a brisk reduction in the ctDNA tumor fraction as well as variant-allele frequencies (VAFs) of all the mutations detected before the start of avelumab. CONCLUSION: Avelumab may achieve rapid and major responses in metastatic MCC. Our study demonstrates that ctDNA mirrors radiological responses and may serve as an ideal companion for diagnosis and disease monitoring in MCC.

Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients.

Synucleinopathies such as Parkinson's disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclein multimers in sporadic PD patients following the classical Braak spreading theory. In this study, we assessed relative levels of disordered and higher-ordered multimeric forms of cytosolic α-synuclein in blood from familial PD with G51D mutations and sporadic PD patients. We used an adapted in vitro-cross-linking protocol for human EDTA-whole blood. The relative levels of higher-ordered α-synuclein tetramers were diminished in blood from familial PD and sporadic PD patients compared to controls. Interestingly, the relative amount of α-synuclein tetramers was already decreased in asymptomatic G51D carriers, supporting the hypothesis that α-synuclein multimer destabilization precedes the development of clinical PD. Our data, therefore suggest that measuring α-synuclein tetramers in blood may have potential as a facile biomarker assay for early detection and quantitative tracking of PD progression.

Measurement invariance of the Arizona Sexual Experience Scale by sexual orientation: comparing the sexual functioning of gay and heterosexual individuals.

BACKGROUND: The assessment of sexual functioning requires accurate and reliable measures as well as short and easy to apply. The Arizona Sexual Experience Scale (ASEX), which provides a quick, easy, and nonintrusive assessment of sexual functioning in men and women, is a clear example of a commonly used scale that satisfies these qualities. AIM: The study sought to examine measurement invariance and differential item functioning (DIF) by sexual orientation of the Spanish version of the ASEX. METHODS: A confirmatory factor analysis was performed on a sample of 1600 adults (800 gay and 800 heterosexual individuals), testing measurement invariance of the ASEX by sexual orientation in men and women separately, and calculating its reliability and DIF. OUTCOMES: The measure provided by the Spanish version of the ASEX is reliable and valid for assessing the sexual functioning of gay men and lesbians, but comparisons by sexual orientation are not recommended for men. RESULTS: The results of the confirmatory factor analysis confirmed the unidimensional structure of the ASEX already found in the Spanish validation with heterosexual people. Measurement invariance showed that, in the men's sample, the factor structure of the ASEX only reached the weak level of invariance, whereas in the women's sample, strict invariance by sexual orientation was reached. The internal consistency reliability was adequate, with better coefficients in women than in men. No significant DIF was observed in either men or women. CLINICAL IMPLICATIONS: Clinicians should further their training in sexual and gender diversity as approaches such as affirmative LGBT psychotherapy gain popularity, and they must have access to assessment instruments that are psychometrically robust enough to be used with this population. STRENGTHS AND LIMITATIONS: This research has some limitations. Because the distribution was administered solely through social media platforms, those without access to social media were unable to participate. Beyond these restrictions, however, the findings are thought to be significant from a research and clinical perspective since measurement invariance is a step that is often excluded when using an instrument validated in a mostly heterosexual sample. CONCLUSION: Validating assessment tools in gay men and lesbians is essential because sexual functioning is a crucial concept in sexual health. The findings of this study suggest that the Spanish version of the ASEX offers valid and reliable measures of sexual functioning for both heterosexual and gay people, though there would be bias in comparing men of both orientations.

Levels of Pro-Inflammatory and Bone-Resorptive Mediators in Periodontally Compromised Patients under Orthodontic Treatment Involving Intermittent Forces of Low Intensities.

During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended. To determine if this kind of treatment is periodontally well tolerated, this study aimed to analyze the production of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, IL-17A, and matrix metalloproteinase (MMP)-8 in periodontal tissues of protruded anterior teeth with reduced periodontal support and undergoing orthodontic treatment. Patients with periodontitis-associated anterior teeth migration received non-surgical periodontal therapy and a specific orthodontic treatment involving controlled low-intensity intermittent orthodontic forces. Samples were collected before periodontitis treatment, after periodontitis treatment, and at 1 week to 24 months of the orthodontic treatment. During the 2 years of orthodontic treatment, no significant differences were detected in the probing depth, clinical attachment level, supragingival bacterial plaque, and bleeding on probing. In line with this, the gingival crevicular levels of RANKL, OPG, IL-6, IL-17A, and MMP-8 did not vary between the different evaluation time-points of the orthodontic treatment. When compared with the levels detected during the periodontitis, the RANKL/OPG ratio was significantly lower at all the analyzed time-points of the orthodontic treatment. In conclusion, the patient-specific orthodontic treatment based on intermittent orthodontic forces of low intensities was well tolerated by periodontally compromised teeth with pathological migration.

Sleep Patterns during the COVID-19 Lockdown in Spain.

BACKGROUND: To mitigate the spread of the coronavirus disease (COVID-19) pandemic, governments around the world adopted exceptional lockdown measures. This led to the disruption of normal life routines, including sleep. The aim of this study was to analyze differences in sleep patterns and subjective variables of sleep quality before and during lockdown. METHODS: A sample of 1673 Spanish adults (30% men; 82% of the total were between 21 and 50 years of age) was evaluated. The following sleep variables were evaluated: Sleep latency, sleep time, number and duration of awakenings, sleep satisfaction, daytime sleepiness, and the manifestation of symptoms related to sleep problems. RESULTS: Although 45% of people changed their sleep schedules (resulting in 42% sleeping longer during lockdown), sleep quality (37.6% worse), daytime sleepiness (28% worse), number of awakenings (36.9% more), and duration of awakenings (45% longer) were markedly worse. Statistical analyses indicated significant differences in all the evaluated sleep variables before and during lockdown in both men and women. Women reported less sleep satisfaction, and more symptoms related to sleep problems than men. CONCLUSIONS: A deterioration in the sleep patterns of the Spanish population, especially women, because of the lockdown declared due to the COVID-19 pandemic.

Measurement Invariance across Sexual Orientation for Measures of Sexual Attitudes.

Despite the growing interest in the study of sexual attitudes across sexual orientation, few studies have tested whether the instruments used to measure them are invariant. This study examined measurement invariance (configural, weak, strong, and strict) across sexual orientation in three different sexual attitude scales: the Sexual Opinion Survey (SOS) to assess erotophilia, the Hurlbert Index of Sexual Fantasy (HISF) to assess attitudes toward sexual fantasies, and the Negative Attitudes Toward Masturbation Inventory (NATMI) to assess negative attitudes toward masturbation. A total of 2293 Spanish adult men and women with different sexual orientations (i.e., heterosexual, bisexual, and gay) participated in the study. The results indicated strict invariance for HISF across sexual orientation and only weak invariance for SOS and NATMI. Differential item functioning was also found in two items of the NATMI scale. Evidence of validity was provided for the three scales that were studied.

Network and Exploratory Factorial Analysis of the Depression Clinical Evaluation Test.

Depression is a highly prevalent disorder with a wide range of symptomatology. Existing instruments for its assessment have only a few items for each factor. The Depression Clinical Evaluation Test (DCET) has been created to cover all depression symptoms at different times (month, year, and always) with several items for each facet. The content validity of this instrument has been judged by experts and, in this paper, we analyse its factorial structure and make a network analysis of it. The test (196 items) was administered to 602 adults without psychological disorders (Mage = 24.7, SD = 8.38, 72% women) both online and on paper. A network was estimated for each time point, using the absolute minimum selection and shrinkage operator. From the factor analysis, 12 factors were established for month, 11 for year, and 10 for always, leaving 94 items. The network analysis showed that the facets of depressive mood, anhedonia, and thoughts of Death, are central to all the estimated networks. The DCET is proposed as a valid and reliable multifactorial instrument to detect the variability of depressive symptoms in adults, guaranteeing its diagnostic usefulness.

Content Validity through Expert Judgment for the Depression Clinical Evaluation Test.

Background/Objective: The evaluation of depression requires valid and reliable measuring instruments, which collect a wide spectrum of symptoms that this disorder displays, in order to carry out an accurate and differential diagnosis. The objective of this work is the construction of the Depression Clinical Evaluation Test (DCET), where affective, somatic, cognitive, behavioral and interpersonal symptoms are considered and also analyze its content validity through an expert judgment. Method: Based on different diagnostic and manual classifications, a specification table for a depression test was established. In its evaluation, 16 experts in Psychological Assessment, Psychometry and/or Psychopathology participated. A total of 300 items were created. The experts had to assess the items according to the criteria of Content, Relevance, Clarity, Comprehension, Sensitivity, and Offensiveness. In addition, 50 adults, evaluated the compression of the items. Results: The degree of understanding for all the items was high and the expert judgment favoured the suppression of 104 items, thus obtaining a shorter measuring instrument with a total of 196 items for ease of application. Conclusions: The content validity of the test is adequate and fits the agreed definition of depression.

Antecedentes: La evaluación de la depresión requiere de instrumentos de medida válidos, fiables y que recojan el amplio espectro de síntomas que este trastorno conlleva, para poder llevar a cabo un diagnóstico certero y diferencial. El objetivo de este trabajo es la construcción del Test de Evaluación Clínica de la Depresión (TECD), que contempla síntomas afectivos, somáticos, cognitivos, conductuales e interpersonales, y analizar su validez de contenido a través de un juicio de expertos. Método: A partir de diferentes clasificaciones diagnósticas y manuales se estableció la tabla de especificación del test para este cuestionario de depresión. En la evaluación de este participaron 16 expertos en Evaluación Psicológica, Psicometría y/o Psicopatología. Se crearon 300 ítems en total, que los expertos tuvieron que valorar atendiendo a los criterios de Contenido, Relevancia, Claridad, Comprensión, Sensitividad y Ofensividad. Además, 50 adultos, valoraron la compresión de los items. Resultados: El grado de comprensión de todos los ítems fue elevado y el juicio de expertos supuso la supresión de 104 ítems, obteniendo así un instrumento de medida más breve, con 196 ítems en total, lo que facilitará su aplicación. Conclusiones: La validez de contenido del test es adecuada y se adapta a la definición de depresión establecida.

Effect of an Interdisciplinary Weight Loss and Lifestyle Intervention on Obstructive Sleep Apnea Severity: The INTERAPNEA Randomized Clinical Trial.

Importance: Obesity is the leading cause of obstructive sleep apnea (OSA); however, the effects of weight loss and lifestyle interventions on OSA and comorbidities remain uncertain. Objective: To evaluate the effect of an interdisciplinary weight loss and lifestyle intervention on OSA and comorbidities among adults with moderate to severe OSA and overweight or obesity. Design, Setting, and Participants: The Interdisciplinary Weight Loss and Lifestyle Intervention for OSA (INTERAPNEA) study was a parallel-group open-label randomized clinical trial conducted at a hospital-based referral center in Granada, Spain, from April 1, 2019, to October 23, 2020. The study enrolled 89 Spanish men aged 18 to 65 years with moderate to severe OSA and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or greater who were receiving continuous positive airway pressure (CPAP) therapy. The sole inclusion of men was based on the higher incidence and prevalence of OSA in this population, the differences in OSA phenotypes between men and women, and the known effectiveness of weight loss interventions among men vs women. Interventions: Participants were randomized to receive usual care (CPAP therapy) or an 8-week weight loss and lifestyle intervention involving nutritional behavior change, aerobic exercise, sleep hygiene, and alcohol and tobacco cessation combined with usual care. Main Outcomes and Measures: The primary end point was the change in the apnea-hypopnea index (AHI) from baseline to the intervention end point (8 weeks) and 6 months after intervention. Secondary end points comprised changes in other OSA sleep-related outcomes, body weight and composition, cardiometabolic risk, and health-related quality of life. Results: Among 89 men (mean [SD] age, 54.1 [8.0] years; all of Spanish ethnicity; mean [SD] AHI, 41.3 [22.2] events/h), 49 were randomized to the control group and 40 were randomized to the intervention group. The intervention group had a greater decrease in AHI (51% reduction; change, -21.2 events/h; 95% CI, -25.4 to -16.9 events/h) than the control group (change, 2.5 events/h; 95% CI, -2.0 to 6.9 events/h) at the intervention end point, with a mean between-group difference of -23.6 events/h (95% CI, -28.7 to -18.5 events/h). At 6 months after intervention, the reduction in AHI was 57% in the intervention group, with a mean between-group difference of -23.8 events/h (95% CI, -28.3 to -19.3 events/h). In the intervention group, 18 of 40 participants (45.0%) no longer required CPAP therapy at the intervention end point, and 6 of 40 participants (15.0%) attained complete OSA remission. At 6 months after intervention, 21 of 34 participants (61.8%) no longer required CPAP therapy, and complete remission of OSA was attained by 10 of 34 participants (29.4%). In the intervention vs control group, greater improvements in body weight (change, -7.1 kg [95% CI, -8.6 to -5.5 kg] vs -0.3 kg [95% CI, -1.9 to 1.4 kg]) and composition (eg, change in fat mass, -2.9 kg [95% CI, -4.5 to -1.3 kg] vs 1.4 kg [95% CI, -0.3 to 3.1 kg]), cardiometabolic risk (eg, change in blood pressure, -6.5 mm Hg [95% CI, -10.3 to -2.6 mm Hg] vs 2.2 mm Hg [95% CI, -2.1 to 6.6 mm Hg]), and health-related quality of life (eg, change in Sleep Apnea Quality of Life Index, 0.8 points [95% CI, 0.5-1.1 points] vs 0.1 points [95% CI, -0.3 to 0.4 points]) were also found at the intervention end point. Conclusions and Relevance: In this study, an interdisciplinary weight loss and lifestyle intervention involving Spanish men with moderate to severe OSA and had overweight or obesity and were receiving CPAP therapy resulted in clinically meaningful and sustainable improvements in OSA severity and comorbidities as well as health-related quality of life. This approach may therefore be considered as a central strategy to address the substantial impact of this increasingly common sleep-disordered breathing condition. Trial Registration: ClinicalTrials.gov Identifier: NCT03851653.

Interrelación Entre Ortodoncia y Periodoncia en Periodonto Reducido. Estabilidad Periodontal Tras 6 Años de Seguimiento / Interrelation Between Orthodontics and Periodontics in Reduced Periodontium. Periodontal Stability After 6 Years of Follow-up

RESUMEN: En pacientes con periodontitis, la migración dentaria patológica es una consecuencia de la pérdida de soporte periodontal. El siguiente reporte de caso aborda el tratamiento periodontal y ortodóncico de una paciente con periodontitis y migración dentaria patológica. El protocolo utilizado fue el protocolo de la Unidad de Ortodoncia y Periodoncia de la Facultad de Odontología de la Universidad de Chile. La estabilidad periodontal se ha mantenido por al menos 6 años luego de finalizado el tratamiento de ortodoncia logran-do funcionalidad y estética de la dentición natural.

ABSTRACT: In patients with periodontitis, pathologic tooth migration is a consequence of loss of periodontal support. The following case report addresses the periodontal and orthodontic treatment of a patient with periodontitis and pathologic tooth migration. The protocol used was the protocol of the Orthodontics and Periodontics Unit of the Faculty of Dentistry of the University of Chile. The periodontal stability has been maintained for at least 6 years after the end of orthodontic treatment, achieving functionality and aesthetics of the natural dentition.

Immunotherapy in microsatellite instability metastatic colorectal cancer: Current status and future perspectives.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent and deadly malignancies worldwide. This specific pathology is composed of various molecular entities, with distinct immunological phenotypes. In addition to KRAS, NRAS, and BRAF mutation status, other druggable alterations such as those in HER2, MET, NTRK, ALK, and ROS1 have been identified in recent years offering new therapeutic options for some patients with CRC. AIM: This review will focus on the molecular biology, immunological fingerprints, and current clinical evidence for the use of immunotherapy in patients with CRC. RELEVANCE FOR PATIENTS: High microsatellite instability (MSI-H) and mutations in mismatch repair genes constitute a new molecular entity within CRC, which is characterized by a high mutational and neoantigen burden, frequent immune cell infiltration, and where immune checkpoint inhibitors have shown high response and survival rates compared to microsatellite stable (MSS) tumors. Indeed, the approval of pembrolizumab in MSI-H tumors was the first agnostic FDA approval in solid tumors. While monotherapy with anti-programmed cell death protein-1 agents achieves objective response rates (ORR) of around 30% and 1-year overall survival (OS) rates of 76%, anti-PD1, and anti-CTLA4 combinations achieve a 55% ORR and a 1-year OS rate of 85%. Several ongoing trials are evaluating the use of different immunotherapy combinations, both in the advanced and early settings and in MSI-h and MSS CRCs.

A Reliability Generalization Meta-analysis of the South Oaks Gambling Screen (SOGS).

BACKGROUND: The South Oaks Gambling Screen (SOGS) is one of the most widely used screening instruments for evaluating addiction to gambling. METHOD: The main objective of this study is to analyze whether the SOGS is a reliable instrument and what characteristics of studies on the SOGS are linked to its reported reliability. RESULTS: A meta-analysis was carried out with 63 studies including 65 independent samples. The mean value of a was .86 (95% CI of .84­.88), with high heterogeneity (I2 = 98.27%). The variables that explain the most heterogeneity were the continent where the study was performed (R2 = .61), application to participants with or without clinical problems (R2 = .58), the form of administration of the questionnaire (R2 = .56), and the standard deviation in the SOGS score (R2 = .13). CONCLUSIONS: The results show that the SOGS is a reliable instrument for evaluating gambling addiction. However, the meta-analysis highlights the need to report the reliability values for each empirical study and to provide a set of recommendations for researchers and professionals who use this instrument.

Aß43 aggregates exhibit enhanced prion-like seeding activity in mice.

When injected into genetically modified mice, aggregates of the amyloid-ß (Aß) peptide from the brains of Alzheimer's disease (AD) patients or transgenic AD mouse models seed cerebral Aß deposition in a prion-like fashion. Within the brain, Aß exists as a pool of distinct C-terminal variants with lengths ranging from 37 to 43 amino acids, yet the relative contribution of individual C-terminal Aß variants to the seeding behavior of Aß aggregates remains unknown. Here, we have investigated the relative seeding activities of Aß aggregates composed exclusively of recombinant Aß38, Aß40, Aß42, or Aß43. Cerebral Aß42 levels were not increased in AppNL-F knock-in mice injected with Aß38 or Aß40 aggregates and were only increased in a subset of mice injected with Aß42 aggregates. In contrast, significant accumulation of Aß42 was observed in the brains of all mice inoculated with Aß43 aggregates, and the extent of Aß42 induction was comparable to that in mice injected with brain-derived Aß seeds. Mice inoculated with Aß43 aggregates exhibited a distinct pattern of cerebral Aß pathology compared to mice injected with brain-derived Aß aggregates, suggesting that recombinant Aß43 may polymerize into a unique strain. Our results indicate that aggregates containing longer Aß C-terminal variants are more potent inducers of cerebral Aß deposition and highlight the potential role of Aß43 seeds as a crucial factor in the initial stages of Aß pathology in AD.

Celia's Encephalopathy (BSCL2-Gene-Related): Current Understanding.

Seipin, encoded by the BSCL2 gene, is a protein that in humans is expressed mainly in the central nervous system. Uniquely, certain variants in BSCL2 can cause both generalized congenital lipodystrophy type 2, upper and/or lower motor neuron diseases, or progressive encephalopathy, with a poor prognosis during childhood. The latter, Celia's encephalopathy, which may or may not be associated with generalized lipodystrophy, is caused by the c.985C >T variant. This cytosine to thymine transition creates a cryptic splicing zone that leads to intronization of exon 7, resulting in an aberrant form of seipin, Celia seipin. It has been proposed that the accumulation of this protein, both in the endoplasmic reticulum and in the nucleus of neurons, might be the pathogenetic mechanism of this neurodegenerative condition. In recent years, other variants in BSCL2 associated with generalized lipodystrophy and progressive epileptic encephalopathy have been reported. Interestingly, most of these variants could also lead to the loss of exon 7. In this review, we analyzed the molecular bases of Celia's encephalopathy and its pathogenic mechanisms, the clinical features of the different variants, and a therapeutic approach in order to slow down the progression of this fatal neurological disorder.

Characteristics of sleep spindles in school-aged children with attention-deficit/hyperactivity disorder.

OBJECTIVE: Attention deficit/hyperactivity disorder (ADHD) is a complex disorder, characterized by different presentations with distinct cognitive and neurobiological characterizations. Here we aimed to investigate whether sleep spindle activity, which has been associated with brain maturation, may be a potential biomarker able to differentiate ADHD presentations in school-aged children (7-11 years). METHOD: Spindle characteristics were extracted from overnight polysomnography in 74 children (27 ADHD-Inattentive [IQ = 96.04], 25 ADHD-hyperactive/impulsive [IQ = 98.9], and 22 ADHD-combined [IQ = 96.1]). We obtained data of the frontal (Fz) and parietal (Pz) derivations using a validated spindle detection algorithm. RESULTS: Children with ADHD showed a higher number and density of slow compared to fast spindles which were more frequent in frontal area. No differences were observed among ADHD presentations for any spindle characteristics. Spindle frequency and density increased with age, indicating an age-dependent maturation of different sleep spindles. However, no associations between IQ and spindle characteristics were observed. CONCLUSIONS: In children with ADHD the spindle characteristics evolve with age but sleep spindle activity does not seem to be a valid biomarker of ADHD phenotypes or general cognitive ability.

Sleep, academic achievement, and cognitive performance in children with attention-deficit hyperactivity disorder: A polysomnographic study.

The objective of this study was to examine the influence of parent-reported and polysomnography (PSG)-measured sleep patterns on the academic and cognitive performance of children with attention-deficit hyperactivity disorder (ADHD). We assessed 91 children (18 girls) diagnosed with ADHD aged 7-11 years (29 ADHD-Inattentive, 32 ADHD-Hyperactive/Impulsive, and 31 ADHD-Combined). The Paediatric Sleep Questionnaire (PSQ) and Paediatric Daytime Sleepiness Scale (PDSS) were used to assess subjective sleep quality, as perceived by parents, and objective sleep variables were assessed by PSG. Cognitive performance was evaluated using the Wechsler Intelligence Scale for Children (WISC), and the final average grade of the last school year was used as a measure of academic performance. Academic performance was predicted by the following sleep variables: Sleep time, time in bed, night awakenings, and daytime sleepiness. The best predictors of cognitive performance in children with ADHD were rapid eye movement latency, light sleep, periodic limb movements index (PLMs), awakenings, and daytime sleepiness. In conclusion, sleep parameters are closely associated with the academic and cognitive functioning of children with ADHD.

Personalizing first-line treatment in advanced colorectal cancer: Present status and future perspectives.

BACKGROUND: Colorectal cancer is one of the most frequent neoplasms worldwide, and the majority of patients are diagnosed in advanced stages. Metastatic colorectal cancer (mCRC) harbors several mutations with different prognostic and predictive values; KRAS, NRAS, and BRAF mutations are the best known. Indeed, RAS and BRAF molecular status are associated with a different response to monoclonal antibodies (Anti-epidermal growth factor receptor and anti-vascular endothelial growth factor receptor agents), which are usually added to chemotherapy in first-line, and thus allow to select the optimal therapy for patients with mCRC. Furthermore, sidedness is an important predictive and prognostic factor in mCRC, which is explained by the different molecular profile of left and right-sided tumors. Recently, microsatellite instability-high has emerged as a predictive factor of response and survival from immune checkpoint inhibitors in mCRC. Finally, several other alterations have been described in lower frequencies, such as human epidermal growth factor receptor-2 overexpression/amplification, PIK3CA pathway alterations, phosphatase and tension homolog loss, and hepatocyte growth factor/mesenchymal-epithelial transition factor pathway dysregulation, with several targeted therapies already demonstrating activity or being tested in currently ongoing clinical trials. AIM: To review the importance of studying the predictive and prognostic roles of the molecular profile of mCRC, the changes occurred in recent years and how they would potentially change in the near future, to guide physicians in treatment decisions. RELEVANCE FOR PATIENTS: Today, several different therapeutic options can be offered to patients in the first-line setting of mCRC. Therapies at present approved or under investigation in clinical trials will be thoroughly reviewed, with special emphasis on the molecular rationale behind them. Understanding the molecular status, resistance mechanisms and potential new druggable targets may allow physicians to choose the best therapeutic option in the first-line mCRC.

A Meta-Analysis of the Generalization of the Reliability of State/Trait Depression Inventory Scores.

BACKGROUND: Depression is a disorder that is highly prevalent nowadays. Within the dimensional explanatory model of depression, the State/Trait Depression Inventory was developed. Its objective is to identify the degree of affectation (state) and the frequency of occurrence (trait) of the affective component of depression. The instrument has proven reliable and comprises two factors in its structure: state and trait, with two euthymia and dysthymia subscales in each one. The objective of this meta-analysis is to find an average alpha for the questionnaire. METHOD: A bibliographical search was conducted on Web of Science and Scopus. Forty-five articles were selected. RESULTS: The alpha ranges from .84 to .89 for all factorizations, and in most studies a bifactorial structure of state and trait depression was found. CONCLUSIONS: The State/Trait Depression Inventory is a reliable and suitable instrument for measuring depression.

Long-term survival of a patient with programmed death ligand 1-negative lung adenocarcinoma and oligoprogressive disease treated with nivolumab and stereotactic body radiation therapy.

Immune-checkpoint inhibitors have shown to prolong survival in patients with metastatic non-small cell lung cancer. Programmed death ligand 1 (PD-L1) expression is associated with a higher probability of response, although some patients with PD-L1 negative tumors may also respond or show durable stabilizations. However, the optimal strategy after progression to immunotherapy (IO) is not yet defined. Patients with oligometastatic disease may benefit from local treatments such as radiotherapy (RT), achieving significant local control rates. In addition, RT is claimed to have numerous immunogenic effects that could synergize with IO. We present the case of a complete responder to nivolumab that after a monotopic adrenal relapse received stereotactic body radiation therapy, followed by maintenance nivolumab achieving a partial response that is still ongoing. Aspects such as mechanisms of acquired resistance to PD-L1 inhibitors, the optimal management after progression, and the potential interplay between IO and RT are briefly reviewed and discussed.