Anti­CGRP monoclonal antibodies in resistant migraine: preliminary real-world effectiveness and clinical predictors of response at two years.

BACKGROUND: Monoclonal antibodies targeting calcitonin gene-related peptide (anti-CGRP mAbs) have shown clinical effectiveness and safety in randomized clinical studies. However, long-term studies in clinical practice remain limited. AIM: To assess the long-term effectiveness, clinical predictors and safety of three anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab) in resistant migraine patients. METHOD: A single-center retrospective study was conducted from December 2019 to June 2023 involving 120 resistant migraine patients who received at least a month of anti-CGRP mAbs treatment. Patients completed a headache diary that included monthly acute medication intake (MAM), monthly migraine days (MMD), adverse events as well as completed Patient-Reported Outcome questionnaires (MIDAS [Migraine Disability Assessment] and Headache Impact Test 6 [HIT-6]). The number of patients achieving a ≥ 50% reduction in monthly migraine days was determined and classified as ≥ 50% responders, and baseline parameters and logistic regression between responders and non-responders were analyzed to identify potential predictors of response. Adverse events were registered in every follow-up. RESULTS: Treatment with anti-CGRP mAbs led to reductions in MIDAS, HIT-6, MMD and MAM from baseline to 6-24 months. At 6-12 months, responders (61% and 57%, respectively) exhibited lower baseline MMD and MAM. Medication overuse  was associated with non-responders from 6 to 24 months and it was identified as a negative predictor of treatment effectiveness (OR 0.23, 95% CI 0.07-0.74; p = 0.014). CONCLUSION: Anti-CGRP mAbs prove effectiveness and safety over a 24-month period in a RM population. Patients with no medication overuse and lower basal MMDs and MAM may respond better to anti-CGRP mAbs.

Impacto en la salud mental en residentes de tres programas de especialización médica de la Universidad de Valparaíso durante la pandemia por COVID-19 / Impact of the COVID-19 pandemic on the mental health of residents of three specialty medical programs

BACKGROUND: COVID-19 pandemic disturbed mental health of healthcare personnel. Residents of the specialization programs could be at risk, since they were reassigned in their functions. Aim: To describe the impact of COVID-19 pandemic on symptoms of depression, stress, anxiety and resilient coping in residents of Anesthesiology, Internal Medicine and Emergency Medicine MATERIAL AND METHODS: Residents were invited to answer an online survey containing the DASS-21 scale for anxiety, stress and depression symptoms and the Brief Resilient Coping Scale (BRCS) for resilience skills. RESULTS: Fifty four out of 90 residents answered the survey. Eighteen to 24% of respondents had symptoms of depression, anxiety and stress at severe and extremely severe levels. Those with severe and extremely severe symptoms had also the lowest score on the BRCS resilience scale. We did not find an association between severity of symptoms and gender. Discussion: A proportion of respondent residents had severe psychological symptoms and lower resilience scores during the COVID-19 pandemic.

[Impact of the COVID-19 pandemic on the mental health of residents of three specialty medical programs]. / Impacto en la salud mental en residentes de tres programas de especialización médica de la Universidad de Valparaíso durante la pandemia por COVID-19.

BACKGROUND: COVID-19 pandemic disturbed mental health of healthcare personnel. Residents of the specialization programs could be at risk, since they were reassigned in their functions. AIM: To describe the impact of COVID-19 pandemic on symptoms of depression, stress, anxiety and resilient coping in residents of Anesthesiology, Internal Medicine and Emergency Medicine Material and Methods: Residents were invited to answer an online survey containing the DASS-21 scale for anxiety, stress and depression symptoms and the Brief Resilient Coping Scale (BRCS) for resilience skills. RESULTS: Fifty four out of 90 residents answered the survey. Eighteen to 24% of respondents had symptoms of depression, anxiety and stress at severe and extremely severe levels. Those with severe and extremely severe symptoms had also the lowest score on the BRCS resilience scale. We did not find an association between severity of symptoms and gender. DISCUSSION: A proportion of respondent residents had severe psychological symptoms and lower resilience scores during the COVID-19 pandemic.

Empirical leucine-to-carbon conversion factors in north-eastern Atlantic waters (50-2000 m) shaped by bacterial community composition and optical signature of DOM.

Microbial heterotrophic activity is a major process regulating the flux of dissolved organic matter (DOM) in the ocean, while the characteristics of this DOM strongly influence its microbial utilization and fate in the ocean. In order to broaden the vertical resolution of leucine-to-carbon conversion factors (CFs), needed for converting substrate incorporation into biomass production by heterotrophic bacteria, 20 dilution experiments were performed in the North Atlantic Ocean. We found a depth-stratification in empirical CFs values from epipelagic to bathypelagic waters (4.00 ± 1.09 to 0.10 ± 0.00 kg C mol Leu-1). Our results demonstrated that the customarily used theoretical CF of 1.55 kg C mol Leu-1 in oceanic samples can lead to an underestimation of prokaryotic heterotrophic production in epi- and mesopelagic waters, while it can overestimate it in the bathypelagic ocean. Pearson correlations showed that CFs were related not only to hydrographic variables such as temperature, but also to specific phylogenetic groups and DOM quality and quantity indices. Furthermore, a multiple linear regression model predicting CFs from relatively simple hydrographic and optical spectroscopic measurements was attempted. Taken together, our results suggest that differences in CFs throughout the water column are significantly connected to DOM, and also reflect differences linked to specific prokaryotic groups.

SEOM clinical guideline on hereditary colorectal cancer (2019).

In the last 2 decades, clinical genetics on hereditary colorectal syndromes has shifted from just a molecular characterization of the different syndromes to the estimation of the individual risk of cancer and appropriate risk reduction strategies. In the last years, new specific therapies for some subgroups of patients have emerged as very effective alternatives. At the same time, germline multigene panel testing by next-generation sequencing (NGS) technology has become the new gold standard for molecular genetics.

Management of the toxicity of chemotherapy and targeted therapies in elderly cancer patients.

The elderly form a very heterogeneous group in relation to their general health state, degree of dependence, comorbidities, performance status, physical reserve and geriatric situation, so cancer treatment in the older patient remains a therapeutic challenge. The physiological changes associated with aging increase the risk of developing a serious toxicity induced by chemotherapy treatment, as well as other undesirable consequences as hospitalizations, dependence and non-compliance with treatment, that can negatively affect survival, quality of life and treatment efficacy. The use of hematopoietic growth factors and other active supportive interventions in the elderly can help prevent and/or alleviate these toxicities. However, we have little data on the efficacy and tolerance of support treatments in the older patient. The objective of this work is to review the most frequent toxicities of oncological treatments in the elderly and their management.

Author Correction: Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer.

Cetuximab is a standard-of-care treatment for RAS wild-type metastatic colorectal cancer (mCRC) but not for those harbor a KRAS mutation since MAPK pathway is constitutively activated. Nevertheless, cetuximab also exerts its effect by its immunomodulatory activity despite the presence of RAS mutation. The aim of this study was to determine the impact of polymorphism FcγRIIIa V158F and killer immunoglobulin-like receptor (KIR) genes on the outcome of mCRC patients with KRAS mutations treated with cetuximab. This multicenter Phase II clinical trial included 70 mCRC patients with KRAS mutated. We found KIR2DS4 gene was significantly associated with OS (HR 2.27; 95% CI, 1.08-4.77; P = 0.03). In non-functional receptor homozygotes the median OS was 2.6 months longer than in carriers of one copy of full receptor. Multivariate analysis confirmed KIR2DS4 as a favorable prognostic marker for OS (HR 6.71) in mCRC patients with KRAS mutation treated with cetuximab. These data support the potential therapeutic of cetuximab in KRAS mutated mCRC carrying non-functional receptor KIR2DS4 since these patients significantly prolong their OS even after heavily treatment. KIR2DS4 typing could be used as predictive marker for identifying RAS mutated patients that could benefit from combination approaches of anti-EGFR monoclonal antibodies and other immunotherapies to overcome the resistance mediated by mutation in RAS.

Spirulina supplementation during the transition period by grazing dairy cattle at tropical highland conditions.

The objective of this experiment was to evaluate the effects of spirulina supplementation on oxidative stress, immunity, and productive performance during the transition period by grazing dairy cattle. Thirty multiparous gestating cows with an initial body weight (BW = 544 ± 57 kg) were enrolled in this experiment and were stratified by expected calving date. Cows were randomly assigned to one of the three experimental groups: (1) control, no supplementation of spirulina; (2) spirulina-15 (15 g/day of spirulina); and (3) spirulina-30 (30 g/day of spirulina). Body weight and body condition score (BCS) were recorded and blood samples were collected at - 21, 1, and 14 days, relative to calving. The day of parturition, colostrum and blood samples from calves were collected to measure IgG concentrations. After parturition milk yield, milk components and somatic cell count were monitored. Body weight, BW loss, BCS, and total antioxidant capacity were not affected by spirulina supplementation (P > 0.23) at any time point measured. Milk yield, milk components, and somatic cell count were not altered by treatment (P > 0.13). Results from this experiment suggest neither positive nor negative effects of spirulina supplementation on oxidative stress and productive performance during the transition period.

First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: Phase II randomised MACRO2 TTD study.

BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.

Impact of Specific Training in Anaphylaxis for Triage Nursing Staff in the Pediatric Emergency Department of a Tertiary Hospital.

BACKGROUND: After a diagnosis of anaphylaxis, patients receive action management plans to prevent and treat new episodes, including attending the emergency department for follow-up or further treatment. In a previous study, we observed that more than half of the children with anaphylaxis were incorrectly prioritized in our Pediatric Emergency Unit (PEU), thus delaying their treatment. In conjunction with our PEU staff, we designed a basic educational intervention (BEI) to try to solve this problem. We analyzed the effect of the intervention on triage of children subsequently diagnosed with anaphylaxis. METHODS: Our BEI consisted of a training lecture given to the PEU triage nurses and the design of a reference card highlighting symptoms and risk factors of anaphylaxis. We included 138 children with a medical diagnosis of anaphylaxis and assessed modifications in their triage priority level and waiting times (WT) before seeing a physician after our intervention. According to the BEI implementation date, 69 children were diagnosed before the intervention (G1) and 69 after (G2). Clinical data were compared to assess the severity of the episodes. RESULTS: There were no differences between the groups. WT decreased (from 8 to 1 minute; P=.03), and the number of correctly identified patients increased after the BEI (36.2% [G1] and 72.2% [G2]; P=.0001). CONCLUSIONS: Our BEI was effective, improving the identification and prioritization of children with anaphylaxis and reducing their WT. We need to pay attention to the functioning of our patients' reference emergency department and establish interdisciplinary measures that enable optimal management of anaphylaxis.

General recommendations paper on the management of older patients with cancer: the SEOM geriatric oncology task force's position statement.

Population aging is associated with greater numbers of older people with cancer. Thanks to treatment advances, not only are more seniors diagnosed with cancer, but there are also more and more older cancer survivors. This upward trend will continue. Given the heterogeneity of aging, managing older patients with cancer poses a significant challenge for Medical Oncology. In Spain, a Geriatric Oncology Task Force has been set up within the framework of the Spanish Society for Medical Oncology (SEOM). With the aim of generating evidence and raising awareness, as well as helping medical oncologists in their training with respect to seniors with cancer, we have put together a series of basic management recommendations for this population. Many of the patients who are assessed in routine clinical practice in Oncology are older. CGA is the basic tool by means of which to evaluate older people with cancer and to understand their needs. Training and the correct use of recommendations regarding treatment for comorbidities and geriatric syndromes, support care, and drug-drug interactions and toxicities, including those of antineoplastic agents, as detailed in this article, will ensure that this population is properly managed.

Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain.

OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

Colour change in a structural ornament is related to individual quality, parasites and mating patterns in the blue tit.

Carry-over effects refer to processes that occur in one season and influence fitness in the following. In birds, two costly activities, namely reproduction and moult, are restricted to a small time window, and sometimes overlap. Thus, colour in newly moulted feathers is likely to be affected by the costs of reproduction. Using models of bird vision we investigated male colour change in a free-living population of blue tits (Cyanistes caeruleus) in three sampling occasions: spring 1, winter and spring 2. We related crown, tail, breast and cheek feather colouration after the moult (winter) to the intensity of infections by blood parasites during reproduction (spring 1). In the following spring (spring 2), we explored mating patterns with respect to changes in feather colour (springs 1 vs. 2). Males that were less intensely infected by the malaria parasite Plasmodium while breeding showed purer white cheek feathers in winter, which may indicate higher feather quality. Increased brightness in the white cheek was associated with better body condition during reproduction. In the following season, males with brighter cheeks paired with females that had noticeably brighter cheek patches compared to the male's previous mate. These results suggest that the conditions experienced during reproduction are likely to affect moult and thus feather colouration, at least in the white patch. High quality individuals may allocate resources efficiently during reproduction increasing future reproductive success through variation in mating patterns. Carry-over effects from reproduction might extend not only to the non-breeding phase, but also to the following breeding season.

Geriatric oncology in Spain: survey results and analysis of the current situation.

INTRODUCTION: Geriatric oncology (GO) is a discipline that focuses on the management of elderly patients with cancer. The Spanish Society of Medical Oncology (SEOM) created a Working group dedicated to geriatric oncology in February 2016. OBJECTIVES: The main goal of this study was to describe the current situation in Spain regarding the management of elderly cancer patients through an online survey of medical oncologists. METHODS: A descriptive survey was sent to several hospitals by means of the SEOM website. A personal e-mail was also sent to SEOM members. RESULTS: Between March 2016 and April 2017, 154 answers were collected. Only 74 centers (48%) had a geriatrics department and a mere 21 (14%) medical oncology departments had a person dedicated to GO. The vast majority (n = 135; 88%) had the perception that the number of elderly patients with cancer seen in clinical practice had increased. Eighteen (12%) oncologists had specific protocols and geriatric scales were used at 55 (31%) centers. Almost all (92%) claimed to apply special management practices using specific tools. There was agreement that GO afforded certain potential advantages. Finally, 99% of the oncologists surveyed believed it and that training in GO had to be improved. CONCLUSIONS: From the nationwide survey promoted by the Spanish Geriatric Oncology Working Group on behalf of SEOM, we conclude that there is currently no defined care structure for elderly cancer patients. There is an increasing perception of the need for training in GO. This survey reflects a reality in which specific needs are perceived.

Importance of tissue sampling, laboratory methods, and patient characteristics for detection of Pneumocystis in autopsied lungs of non-immunosuppressed individuals.

To understand the epidemiological significance of Pneumocystis detection in a lung tissue sample of non-immunosuppressed individuals, we examined sampling procedures, laboratory methodology, and patient characteristics of autopsy series reported in the literature. Number of tissue specimens, DNA-extraction procedures, age and underlying diagnosis highly influence yield and are critical to understand yield differences of Pneumocystis among reports of pulmonary colonization in immunocompetent individuals.

Diagnosis and staging of pancreatic ductal adenocarcinoma.

The management of pancreatic ductal adenocarcinoma (PDAC) is a major public health concern worldwide. Currently, most PDAC patients are diagnosed in advanced stages. The signs and symptoms of the disease, except for jaundice, are non-specific. Thus, the current challenge is to identify earlier those individuals for whom specific screening tools and specific treatments would be beneficial. On the basis of the recommendations of the group of experts of multiple medical specialties of the GALLgo Project, the patients with PDAC should be managed by a multidisciplinary team to assess the personal and family history, the best diagnostic and staging procedures and consider all important aspects for treatment decisions. In this article, the group of experts proposes strategies to shorten the diagnosis times in PDAC patients.

La somatización y conversión en la adolescencia: Un desafío diagnóstico y terapéutico en la consulta / Somatization and conversion in adolescence: A diagnostic and therapeutic challenge in the consultation

El término somatización está muy extendido en el campo de la clínica psicológica y psiquiátrica. Desde el punto de vista nosográfico la somatización y la conversión se encuentran conceptualizadas en el Manual Diagnóstico y Estadístico de las Enfermedades mentales (DSM-IV-TR) dentro de los Trastornos Somatomorfos. Los trastornos Somatomorfos (TS) agrupan diversos cuadros con una característica en común: la presencia de síntomas somáticos vinculados a un malestar psíquico y deterioro significativo, presentándose frecuentemente en niños y adolescentes. Los síntomas se corresponden con dolencias simples hasta cuadros funcionales invalidantes no explicados por una condición médica general, consumo de sustancias, simulación u otra patología mental. La prevalencia de los TS en la adolescencia ha aumentado en las últimas décadas, representando un desafío clínico y terapéutico para el médico por su dificultad clínica y general desconocimiento (AU)

The term somatization is a broad concept in the field of clinical psychology and psychiatry. From the nosographic point of view, somatization and conversion are conceptualized in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IVTR) within the somatoform disorders (SD) characterized by the presence of somatic symptoms associated with psychic pain and significant deterioration, often seen in children and adolescents. The symptoms range from simple discomfort to invalidating functional impairment unexplained by the general medical condition, substance abuse, and simulation or any other mental disorder. Prevalence of SD in adolescence has increased over the past decades, becoming a therapeutic and clinical challenge due to clinical difficulties and lack of unawareness of the disorde (AU)