[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.

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.

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.

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.

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

Immune modulation by the hepatitis C virus core protein.

Hepatitis C virus (HCV) infection is currently the most important cause of chronic viral hepatitis in the world and one of the most frequent indications for liver transplantation. HCV uses different strategies to evade the innate and adaptive immune response, and this evasion plays a key role in determining viral persistence. Several HCV viral proteins have been described as immune modulators. In this review, we will focus on the effect of HCV nucleocapsid core protein in the function of immune cells and its correlation with the findings observed in HCV chronically infected patients. Effects on immune cell function related to both extracellular and intracellular HCV core localization will be considered. This review provides an updated perspective on the mechanisms involved in HCV evasion related to one single HCV protein, which could become a key tool in the development of new antiviral strategies able to control and/or eradicate HCV infection.

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.

Refinement of screening for familial pancreatic cancer.

OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined. METHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed. RESULTS: 253 IAR with a median age of 48 (25-81) years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152) months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45 years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50 years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50 years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12 months (n=180) or IAR that decided to be screened at ≥24 months intervals (n=30). CONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50 years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.

Variations of B cell subpopulations in peripheral blood of healthy Mexican population according to age: Relevance for diagnosis of primary immunodeficiencies.

BACKGROUND: Peripheral blood B cells include lymphocytes at various stages of differentiation, each with a specific function in the immune response. All these stages show variations in percentage and absolute number throughout human life. The numbers and proportions of B subpopulation are influenced by factors such as gender, age, ethnicity, and lifestyle. This study establishes reference values according to age of peripheral blood B cell subtypes in healthy Mexican population. METHODS: Peripheral blood from healthy new-borns and adults were analysed for total B cell subpopulations, using surface markers such as CD19, IgM, IgD, CD21, CD24, CD27, and CD38, to identify naïve, memory with and without isotype switch, double-negative, transitional, and plasmablast cells. RESULTS: We observed a significant variation in terms of frequency and absolute counts between all groups analysed. Values from each B cell subpopulation show variations according to age. CONCLUSIONS: In order to attempt to elucidate reference values for B cell subpopulation, the present study evaluated a population sample of healthy blood donors from this region. Values reported here can also be used as a tool for diagnosis of diseases in which B cell maturation is affected.

Genetic characterization of oropharyngeal trichomonad isolates from wild birds indicates that genotype is associated with host species, diet and presence of pathognomonic lesions.

Oropharyngeal trichomonad isolates of wild birds from Spain were studied. A total of 1688 samples (1214 of predator birds and 474 of prey species) from wildlife recovery centres and scientific bird-ringing campaigns were analysed from 2011 to 2013. The overall infection prevalence was 20.3% (11.4% in predator birds and 43.3% in prey species). Pathognomonic lesions were present in 26% of the infected birds (57.3% in predator birds and 4.9% in prey species). The most commonly parasitized species were the goshawk (Accipiter gentilis, 74.5%) and the rock pigeon (Columba livia, 79.4%). Host species in which the parasite has not been previously analysed by polymerase chain reaction and sequencing in Spain are also reported: Columba palumbus, Streptopelia turtur, Pica pica, A. gentilis, Accipiter nisus, Asio otus, Bubo bubo, Buteo buteo, Circus aeruginosus, Circus cyaneus, Falco naumanni, Falco peregrinus, Neophron percnopterus, Otus scops, Pernis apivorus and Strix aluco. Sequence analysis of the ITS1/5.8S/ITS2 region revealed five different genotypes and also some mixed infections. A relationship between genotype and host species was observed, but only two genotypes (ITS-OBT-Tg-1and ITS-OBT-Tg-2) were widely distributed. Genotype ITS-OBT-Tg-1 was most frequently found in predator birds and statistically associated with pathognomonic lesions. Non-strict ornithophagous species were at higher risk to develop disease than ornithophagous ones. Genotypes ITS-OBT-Tcl-1 and ITS-OBT-Tcl-2 are new reports, and ITS-OBT-Tvl-5 is reported for the first time in Spain. They showed higher genetic homology to Trichomonas canistomae and Trichomonas vaginalis than to Trichomonas gallinae, indicating the possibility of new species within this genus.

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.

Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment.

BACKGROUND: Desensitization to antineoplastic agents is becoming a standard of care. Efforts to establish and improve these techniques are being made at many institutions. Our aims are to evaluate a new rapid desensitization protocol designed to be shorter (approximately 4 h) and safer (reducing hazardous drugs exposure risks) and to assess the oxaliplatin-specific immunoglobulin E (IgE) as a novel diagnostic tool. METHODS: Prospective, observational, longitudinal study with patients who, for a 1-year period, suffered reactions to antineoplastic agents and were referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were included or excluded as desensitization candidates after anamnesis, skin testing, risk assessment, and graded challenge. Specific IgE was determined in oxaliplatin-reactive patients. Candidate patients were desensitized using the new RCUH rapid desensitization protocol. RESULTS: Of 189 intravenous rapid desensitizations, 188 were successfully accomplished in the 23 patients who met inclusion criteria for desensitization (of 58 referred patients). No breakthrough reactions occurred in 94% of desensitizations, and most breakthrough reactions were mild. In 10 oxaliplatin-reactive patients, 38 desensitizations were successfully accomplished. Sensitivity for oxaliplatin-specific IgE was 38% (0.35UI/l cutoff point) and 54% (0.10UI/l cutoff point); specificity was 100% for both cutoff points. CONCLUSIONS: In the hands of a Desensitization Program, managed by drug desensitization experts, this new protocol has proven an effective therapeutic tool for hypersensitivity to several antineoplastic agents (oxaliplatin, carboplatin, paclitaxel, docetaxel, cyclophosphamide, and rituximab); moreover, it improves safety handling of hazardous drugs. We report the first large series of oxaliplatin desensitizations. Oxaliplatin-specific IgE determination could be helpful.

A phase I study of sunitinib in combination with FOLFIRI in patients with untreated metastatic colorectal cancer.

BACKGROUND: This study evaluated the maximum tolerated dose (MTD) of sunitinib, a multitargeted tyrosine kinase inhibitor, combined with FOLFIRI (irinotecan 180 mg/m2 given over 90 min i.v. and l-leucovorin 200 mg/m2 given over 120 min on day 1, followed by 5-FU 400 mg/m2 bolus and then 2400 mg/m2 infused over 46 h) in untreated metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: In this multicentre, phase I, open-label, dose-finding trial, FOLFIRI was administered every 2 weeks. Two sunitinib regimens were explored: Schedule 4/2 (4 weeks on, 2 weeks off; 37.5 and 50 mg/day) and continuous daily dosing (CDD; 37.5 and 25 mg/day). Dose-limiting toxic toxicities (DLTs) were evaluated during weeks 1-6. Efficacy was a secondary objective. RESULTS: Thirty-seven patients were enrolled. The 37.5 mg/day Schedule 4/2 cohort had zero of six DLTs, was expanded by 15 patients and declared the MTD. The MTD was exceeded at all other sunitinib doses and schedules; DLTs included febrile neutropenia (n=1), grade 4 neutropenia (n=4) and grade 3 deep vein thrombosis with grade 4 neutropenia (n=1). At the MTD, non-haematologic grade 3/4 adverse events with a frequency of >10% were diarrhoea, vomiting and lethargy, and the objective response rate was 57.9% (95% confidence interval 33.5-79.7). CONCLUSIONS: The MTD of sunitinib combined with FOLFIRI in chemotherapy-naive mCRC was 37.5 mg/day on Schedule 4/2. CDD of sunitinib at 37.5 or 25 mg/day plus FOLFIRI was not feasible.

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.

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.

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.

Ab initio study of the elastic properties of single and polycrystal TiO(2), ZrO(2) and HfO(2) in the cotunnite structure.

In this work, we study theoretically the elastic properties of the orthorhombic (Pnma) high-pressure phase of IV-B group oxides: titania, zirconia and hafnia. By means of the self-consistent SIESTA code, pseudopotentials, density functional theory in the LDA and GGA approximations, the total energies, hydrostatic pressures and stress tensor components are calculated. From the stress-strain relationships, in the linear regime, the elastic constants C(ij) are determined. Derived elastic constants, such as bulk, Young's and shear modulus, Poisson coefficient and brittle/ductile behavior are estimated with the polycrystalline approach, using Voigt-Reuss-Hill theories. We have found that C(11), C(22) and C(33) elastic constants of hafnia and zirconia show increased strength with respect to the experimental values of the normal phase, P 2(1)/c. A similar situation applies to titania if these constants are compared with its normal phase, rutile. However, shear elastic constants C(44), C(55) and C(66) are similar to the values found in the normal phase. This fact increases the compound anisotropy as well as its ductile behavior. The dependence of unit-cell volumes under hydrostatic pressures is also analyzed. P-V data, fitted to third-order Birch-Murnaghan equations of state, provide the bulk modulus B(0) and its pressure derivatives B'(0). In this case, LDA estimations show good agreement with respect to recent measured bulk moduli of ZrO(2) and HfO(2). Thermo-acoustic properties, e.g. the propagation speed of transverse, longitudinal elastic waves together with associated Debye temperatures, are also estimated.

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.