Search

Introduction. Some causative agents of saprozoonotic infections can multiply in the external environment (water reservoirs, soils, plants), as well as in animals, including microorganisms of the genus Yersinia. Material and methods. Isolation and identification of Y. pseudotuberculosis was carried out in accordance with the instructions on “Epidemiology, laboratory diagnosis of yersiniosis, organization and conduct of preventive and anti-epidemiological measures”. Antibiotic sensitivity was performed via the disc diffusion method in accordance with EUCAST and national guidelines. Biofilm formation was tested using the spectrophotometric assay. Results. It was established that the studied cultures showed a decrease in the level of saccharolytic activity during cultivation at a temperature of +37°C in comparison with the results obtained at 25°C, changes in sensitivity to antibiotics depending on the temperature of cultivation were revealed. It was established that Y. pseudotuberculosis cultures were able to form denser (λ 570) biofilms when cultured at 25°C, in comparison with biofilms formed at 37°C. Conclusions. Biological characteristics of the studied Y. pseudotuberculosis isolates (changes in the saccharolytic activity, the level of sensitivity to antibiotics and the formation of biofilms were revealed) depends on the cultivation conditions.

Survey on solar drying of safou pulp. Preliminary results. The consumption of safou, the fruit of Dacryodes edulis is very common in the entire Gulf of Guinea and is subject to a large trade in countries such as Cameroon, Congo, Gabon and Zaire. The fruit is very fragile with a post haverest loss of more than 50 % in the Congo. Solar dring is the only conservation method well managed by the local population but the resulting products have doubious hygenic quality. In order to appreciate the effect of drying on the product quality and in order to improve the traditional processes we have studied both the variation of residual water in the pulp and the acid index and the color of the oil. Drying with a stove (between 70 to 90°C) and the solar drying give identical products in spite of some small differences in the dehydration mechanism. The resulting products have satisfying qualities : less than 1 % water content, acide index less than 4, optical density around 0, 3 at 400 nm in 25 g/1 cyclohexane. The product can be directly eaten after rehydration or reused as raw material for the extraction of oil from pulp.

Introduction. The serotoninergic system seems to be implicated in characteristic symptoms of borderline personality disorder (BPD) such as affective instability, impulsivity or suicide. Some studies suggest an association between serotonin transporter gene (5-HTT) polymorphisms and some BPD symptoms. Short allele (S) of the 5-HTTLPR polymorphism in the promoter region has been shown to be associated with impulsivity, aggressive behavior, anxiety and neuroticism. Of the variable number of tandem repeat (VNTR) polymorphism in intron 2, BPD patients showed higher frequencies of the allele with the 10 repeats. The aim of this study was to determine the association between 5-HTTLPR and VNTR polymorphism of 5-HTT and personality traits in borderline personality disorder. Method. A total of 65 BPD patients diagnosed by means of semi-structured interviews SCID-II and DIB-R were included. Two common polymorphisms of 5-HTT were genotyped: the 5-HTTLPR in the promoter region and VNTR in intron 2. Personality traits were assessed by the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Results. Patients with L allele (L/S or L/L) in the 5-HTTLPR polymorphism showed lower scores on the subscale of liking parties and friends. Patients with the allele with 10 repeat of the VNTR polymorphism, showed lower scores in impulsivity, sensation seeking and in the subscale liking of parties and friends. Conclusions. The results suggest a significant association between the 5-HTT gene and some personality traits in BPD. This gene may play a role in the etiology of borderline personality disorder. [ABSTRACT FROM AUTHOR]

Background: Acute interstitial nephritis (AIN) related to immune checkpoint inhibitors (ICI-AIN) has a not completely understood pathophysiology. Our objectives were to analyze possible biomarkers for the differentiation between acute tubular necrosis (ATN) and AIN, especially in cancer patients, and to study the participation of the immune checkpoint pathway in ICI-AIN., Methods: We performed an observational study. We recruited patients with incident diagnosis of ICI-AIN ( n  = 19). We measured soluble PD-1 (sPD-1), sPD-L1, and sPD-L2 in serum and urine at diagnosis and compared to it patients with non-ICI-related AIN (non-ICI-AIN) ( n  = 18) and ATN ( n  = 21). The findings were validated in an independent cohort from another institution ( n  = 30). Also, we performed PD-L1 and PD-L2 immunostaining of kidney biopsies from patients with ICI-AIN and compared to patients with non-ICI-AIN., Results: Urinary sPD-1 (usPD-1) was higher in patients with AIN compared to ATN ( P  = .03). Patients with AIN also showed higher serum sPD-1 (ssPD-1) than patients with ATN ( P  = .021). In cancer patients, usPD-1 <129.3 pg/ml had a 71.43% sensitivity and 94.44% specificity to differentiate ATN from ICI-AIN, with a likelihood ratio of 12.86. In the external validation cohort, the same cutoff showed a sensitivity of 80%. In kidney biopsies, patients with ICI-AIN showed higher density of PD-L1 positive tubules than patients with non-ICI-AIN ( P  = .02). The proportion of patients having >2.64/mm 2 PD-L2 positive tubules was higher among patients with ICI-AIN compared to non-ICI-AIN ( P  = .034). There was a positive correlation ( P  = .009, r  = 0.72) between usPD-1 and the number of PD-L1 positive tubules., Conclusions: UsPD-1 and ssPD-1 are higher in AIN than ATN. Moreover, there was a strong correlation between usPD-1 and renal tubular PD-L1 expression. Our findings suggest a role of usPD-1 as non-invasive biomarker to differentiate ICI-AIN from ATN, especially in cancer patients, which has been confirmed in an external validation cohort., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Introduction: Immune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2-5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients., Methods: Twenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression., Results: Cisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity., Conclusions: Only mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker., (© 2024. The Author(s).)

Introduction: There is a need to implement routine perinatal mental health screening in Spain. Therefore, it is necessary to systematise the detection of depressive and anxious symptoms in pregnancy and postpartum using the same instrument. The Edinburgh Postnatal Stress Depression Scale (EPDS) is frequently used as a rapid, effective and cross-culturally validated screening tool for perinatal depression. In several countries, an Anxiety subscale, the EPDS-A, was identified within the EPDS. Although the factorial structure of the EPDS has been investigated in Spanish population, the EPDS-A has not yet been validated. This study aimed to validate the EPDS-A as a measure of perinatal anxiety in Spanish population., Methods: 161 women were evaluated with the EPDS and the State-Trait Anxiety Inventory (STAI) during pregnancy and postpartum. Confirmatory factor analysis (CFA) was used to confirm the trifactorial structure of the EPDS, comprising the dimensions of Depression, Anhedonia and Anxiety. Likewise, the invariance of the trifactorial model between pregnancy and postpartum was tested. Finally, the correlations between the EPDS-A and the STAI subscales (State Anxiety and Trait Anxiety) were calculated., Results: The Exploratory factor analysis (EFA) driven three-factor structure of the EPDS, consisting of an Anhedonia factor (Items 1, 2, and 10), an Anxiety factor (Items 3, 4, 5, and 6) and a Depression factor (Items 7, 8, and 9), was the best measurement model for the current data compared to the alternative model tested [χ 2  = 34.592, df  = 32, p  = 0.34; χ 2 / df  = 1.08; RMSEA = 0.023, 90% Confidence Interval [CI] [0.000, 0.064], CFI = 0.996, GFI = 0.960]. The model's invariance between pregnant and postpartum women was confirmed. The existence of an Anxiety subscale within the EPDS was also confirmed. The scores obtained with the EPDS-A correlated moderately with scores on both subscales of the STAI during pregnancy and after delivery. Using the STAI as a criterion and prioritising the instrument's sensitivity, a cut-off point of 4 points was established for the EPDS-A., Conclusion: Our results confirm the trifactorial structure of the EPDS in Spanish population. The Anxiety subscale was validated for routine perinatal mental health screening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gomà, Gordo, Cozodoy, Iriarte, Prims, Ferrer, Sánchez, Llairó and Arias-Pujol.)

Maternal representations play a key role in intrapsychic conflicts relating to accession to parenthood and in the formation of the mother-baby bond. Around the birth of the child, the shadows of past objects are cast on the baby and the parent's self-image. Mother-baby psychoanalytic psychotherapy helps us to understand internal conflicts that tend to interfere with the mother's representations of her child or of herself as a mother, as well as aiming to reduce the risk of difficulties for the child. Through a clinical case, this article explores the development of maternal representations in a course of parenthood-centred psychotherapy that begins during pregnancy and ends 11 months after the baby's birth. The psychic change carried out by the mother frees the mother-baby bond from the projections of the past. Excerpts from clinical sessions illustrate mother-baby interactions during the session, the projection of the mother's internal objects on to the baby, and the elaboration and reintrojection of the mother's internal conflicts. Changes in the mother's representations were measured both qualitatively and quantitatively using the 'R' interview, which allows various dimensions of these representations to be measured on a Likert scale.

The treatment of head and neck and salivary gland tumours is complicated and is constantly evolving. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein-Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica - SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica - SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers., (Copyright © 2022. Publicado por Elsevier España, S.L.U.)

The treatment of head and neck and salivary gland tumours is complicated and evolves constantly. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein-Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica-SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers., (© 2022. The Author(s).)

Systemic lupus erythematosus is a complex autoimmune disorder mostly mediated by B-cells in which costimulatory signals are involved. This immune dysregulation can cause tissue damage and inflammation of the kidney, resulting in lupus nephritis and chronic renal failure. Given the previous experience reported with CTLA4-Ig as well as recent understanding of the PD-1 pathway in this setting, our group was encouraged to evaluate, in the NZBWF1 model, a human fusion recombinant protein (Hybri) with two domains: CTLA4, blocking the CD28-CD80 costimulatory pathway, and PD-L2, exacerbating the PD-1-PD-L2 coinhibitory pathway. After achieving good results in this model, we decided to validate the therapeutic effect of Hybri in the more severe MRL/lpr model of lupus nephritis. The intraperitoneal administration of Hybri prevented the progression of proteinuria and anti-dsDNA antibodies to levels like those of cyclophosphamide and reduced the histological score, infiltration of B-cells, T-cells, and macrophages and immune deposition in both lupus-prone models. Additionally, Hybri treatment produced changes in both inflammatory-related circulating cytokines and kidney gene expression. To summarize, both in vivo studies revealed that the Hybri effect on costimulatory-coinhibitory pathways may effectively mitigate lupus nephritis, with potential for use as a maintenance therapy.

Achieving fast immunosuppression blood exposure after kidney transplantation is key to abrogating both preformed and de novo anti-donor humoral and cellular alloresponses. However, while tacrolimus (TAC) is the cornerstone immunosuppressant inhibiting adaptive alloimmunity, its blood exposure is directly impacted by different single-nucleotide polymorphisms (SNPs) in CYP3A TAC-metabolizing enzymes. Here, we investigated how functional TAC-CYP3A genetic variants ( CYP3A4*22 / CYP3A5*3 ) influence the main baseline clinical and immunological risk factors of biopsy-proven acute rejection (BPAR) by means of preformed donor-specific antibodies (DSAs) and donor-specific alloreactive T cells (DSTs) in a large European cohort of 447 kidney transplants receiving TAC-based immunosuppression. A total of 70 (15.7%) patients developed BPAR. Preformed DSAs and DSTs were observed in 12 (2.7%) and 227 (50.8%) patients, respectively. According to the different CYP3A4*22 and CYP3A5*3 functional allele variants, we found 4 differential new clusters impacting fasting TAC exposure after transplantation; 7 (1.6%) were classified as high metabolizers 1 (HM1), 71 (15.9%) as HM2, 324 (72.5%) as intermediate (IM), and 45 (10.1%) as poor metabolizers (PM1). HM1/2 showed significantly lower TAC trough levels and higher dose requirements than IM and PM (p < 0.001) and more frequently showed TAC underexposure (<5 ng/ml). Multivariate Cox regression analyses revealed that CYP3A HM1 and IM pharmacogenetic phenotypes (hazard ratio (HR) 12.566, 95% CI 1.99-79.36, p = 0.007, and HR 4.532, 95% CI 1.10-18.60, p = 0.036, respectively), preformed DSTs (HR 3.482, 95% CI 1.99-6.08, p < 0.001), DSAs (HR 4.421, 95% CI 1.63-11.98, p = 0.003), and delayed graft function (DGF) (HR 2.023, 95% CI 1.22-3.36, p = 0.006) independently predicted BPAR. Notably, a significant interaction between T-cell depletion and TAC underexposure was observed, showing a reduction of the BPAR risk (HR 0.264, 95% CI 0.08-0.92, p = 0.037). Such variables except for DSAs displayed a higher predictive risk for the development of T cell-mediated rejection (TCMR). Refinement of pretransplant monitoring by incorporating TAC CYP3A SNPs with preformed DSAs as well as DSTs may improve current rejection-risk stratification and help induction treatment decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer L.R has declared a shared affiliation with the author T.J to the handling editor at the time of review., (Copyright © 2022 Crespo, Vidal-Alabró, Jouve, Fontova, Stein, Mocka, Meneghini, Sefrin, Hruba, Gomà, Torija, Donadeu, Favà, Cruzado, Melilli, Moreso, Viklicky, Bemelman, Reinke, Grinyó, Lloberas and Bestard.)

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) represent a distinct clinical entity compared with HPV-negative tumors with particular regard to treatment response and survival outcome. The aim of this study was to assess the AmpFire Multiplex HR-HPV tests, for the detection and genotyping of 15 high-risk (HR) HPV types in formalin-fixed, paraffin-embedded (FFPE) samples and identify HPV-driven OPSCC. DNA from 160 OPSCC FFPE specimens plus 23 samples from other head and neck primary sites was tested. Results were compared with those obtained using Linear Array HPV-DNA Genotyping Test. Linear Array and AmpFire Multiplex HR-HPV tests showed, for all samples and specifically for OPSCCs, an overall concordance agreement of 98.9% and 99.4% and a Cohen κ coefficient of 0.972 and 0.984, respectively. A concordance of 100% for HPV16 and HPV18 was observed. The overall agreement between p16 INK4a overexpression and HPV detection by the AmpFire Multiplex HR-HPV assay in 145 OPSCC samples was 93.8%, with a Cohen κ coefficient of 0.848. The AmpFire HPV Tests are simple assays for detection and genotyping of HPV-DNA in OPSCC FFPE samples and can be easily implemented in the clinical practice setting for HPV-DNA detection., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

mRNA-based vaccines have dramatically shifted the course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. IgA nephropathy (IgAN) flare is the most reported renal adverse effect after the administration of these vaccines. Unraveling the mechanistic pathways leading to these flares is necessary to confirm a causal association. Herein, we report 2 cases of IgAN flare after SARS-CoV-2 vaccination in patients previously diagnosed with IgAN. We describe and compare the clinical and analytical features of the disease at the time of the diagnostic with the post-vaccine flare. In addition, we obtained serum and urine of these patients at the moment of the flare and determined the levels of IL-2, TNF-α, and IFNγ using a multiplex bead-based assay. As diseased controls, we included n = 13 patients diagnosed with IgAN who had available serum and urine samples at the moment of the diagnostic stored in our biobank. We also included 6 healthy controls. Compared to the first episode, postvaccination flares were more severe in terms of peak serum creatinine, albuminuria, and urinary erythrocyte count. The histological lesions found at the biopsy performed during the post-vaccine flare were similar to those found at the diagnostic. One of the patients who suffered a post-vaccine flare showed increased serum IL-2 and TNFα compared to the IgAN-diseased controls and the healthy controls. In conclusion, although several cases of post-vaccine IgAN flares have been reported, there are no mechanistic studies on the occurrence of these flares. We here suggest that hyperactivation of the Th1 pathway may be involved, but larger studies with more refined methods for numerical and functional Th1 lymphocytes evaluation are required., (© 2022 S. Karger AG, Basel.)

Aim: To determine the prevalence of anxiety-depressive symptomatology and associated risk factors in a population of pregnant women in the low-income neighborhood of Roquetes (Barcelona, Spain)., Design: Quasi-experimental, cross-sectional study., Location: The study was carried out at the Primary Care Center, Roquetes Canteres, Barcelona., Participants: Between 2015 and 2017, all pregnant women who visited the Sexual and Reproductive Care Team in Primary Care (ASSIR) or their Family Physician (FP) were invited to take part in a study if they met the following criteria: (a) over 18 years old (b) able to understand in any of the 4 study languages. Of a total of 239 gestating women, 19 declined to participate, 14 moved away from the area and 16 underwent voluntary termination of pregnancy, leaving a sample of 190 subjects., Material and Methods: The Edinburgh Postnatal Depression Scale (EPDS) was used to detect depressive symptomatology, the State-Trait Anxiety Inventory (STAI) was used to assess anxiety, and a sociodemographic data questionnaire was administered. Once all descriptive demographic data from the whole sample was analyzed, baseline clinical and demographic characteristics were compared using the independent t-test for continuous variables and the chi-squared analysis for categorical variables., Results: The t-test showed that 48% of pregnant women presented an at-risk degree of anxiety-depressive symptomatology, double that found in the general population. Applying a chi-squared test to the at-risk and non-risk groups revealed associated prenatal risk factors including: having a history of violence; living in a rented room, mistreatment in infancy and mental health issues. The ROC curves analysis obtained a cutoff point score of 4 Accumulated Associated Factors (AAF) (AUC 0.765, p  < .001, 57% sensitivity and 79% specificity)., Conclusions: Our study shows that rates of anxiety-depressive symptomatology in a population with considerable socio-economic deprivation can more than double. AAF in the population at risk of anxiety and depression were detected, highlighting the need to allocate resources to identification and prevention during pregnancy. This requires the involvement of a multidisciplinary, professional team with a biopsychosocial perspective.

Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Acute kidney injury in patients who suffer a malignancy is a common complication. Due to its high prevalence and effective treatment, one of the most frequent causes that both oncologists and nephrologists must be aware of is acute tubulointerstitial nephritis (ATIN). ATIN is an immunomediated condition and the hallmark of the disease, with the presence of a tubulointerstitial inflammatory infiltrate in the renal parenchyma. This infiltrate is composed mainly of T lymphocytes that can be accompanied by macrophages, neutrophils, or eosinophils among other cells. One of the major causes is drug-related ATIN, and some antineoplastic treatments have been related to this condition. Worthy of note are the novel immunotherapy treatments aimed at enhancing natural immunity in order to defeat cancer cells. In the context of the immunosuppression status affecting ATIN patients, some pathogen antigens can trigger the development of the disease. Finally, hematological malignancies can also manifest in the kidney leading to ATIN, even at the debut of the disease. In this review, we aim to comprehensively examine differential diagnosis of ATIN in the setting of a neoplastic patient.

Purpose: This study aimed to assess the efficacy of the combination of nivolumab (nivo) plus ipilimumab (ipi) as a first-line therapy with respect to the 12-month overall survival (OS) in patients with metastatic uveal melanoma (MUM) who are not eligible for liver resection., Methods: This was a single-arm, phase II trial led by the Spanish Multidisciplinary Melanoma Group (GEM) on nivo plus ipi for systemic treatment-naïve patients of age > 18 years, with histologically confirmed MUM, Eastern Cooperative Oncology Group-PS 0/1, and confirmed progressive metastatic disease (M1). Nivo (1 mg/kg once every 3 weeks) and ipi (3 mg/kg once every 3 weeks) were administered during four inductions, followed by nivo (3 mg/kg once every 2 weeks) until progressive disease, toxicity, or withdrawal. The primary end point was 12-month OS. OS, progression-free survival (PFS), and overall response rate were evaluated every 6 weeks using RECIST (v1.1). Safety was also evaluated. Logistic regression and Cox proportional hazard models comprising relevant clinical factors were used to evaluate the potential association with response to treatment and survival. Cytokines were quantified in serum samples for their putative role in immune modulation/angiogenesis and/or earlier evidence of involvement in immunotherapy., Results: A total of 52 patients with a median age of 59 years (range, 26-84 years) were enrolled. Overall, 78.8%, 56%, and 32% of patients had liver M1, extra-liver M1, and elevated lactate dehydrogenase. Stable disease was the most common outcome (51.9%). The primary end point was 12-month OS, which was 51.9% (95% CI, 38.3 to 65.5). The median OS and PFS were 12.7 months and 3.0 months, respectively. PFS was influenced by higher LDH values., Conclusions: Nivo plus ipi in the first-line setting for MUM showed a modest improvement in OS over historical benchmarks of chemotherapy, with a manageable toxicity profile.