BackgroundThe main goal of the current work was to infer the demographic history of seven Spanish goat breeds (Malagueña, Murciano-Granadina, Florida, Palmera, Mallorquina, Bermeya and Blanca de Rasquera) based on genome-wide diversity data generated with the Illumina Goat SNP50 BeadChip (population size, N = 176). Five additional populations from Europe (Saanen and Carpathian) and Africa (Tunisian, Djallonké and Sahel) were also included in this analysis (N = 80) for comparative purposes.ResultsOur results show that the genetic background of Spanish goats traces back mainly to European breeds although signs of North African admixture were detected in two Andalusian breeds (Malagueña and Murciano-Granadina). In general, observed and expected heterozygosities were quite similar across the seven Spanish goat breeds under analysis irrespective of their population size and conservation status. For the Mallorquina and Blanca de Rasquera breeds, which have suffered strong population declines during the past decades, we observed increased frequencies of large-sized (ROH), a finding that is consistent with recent inbreeding. In contrast, a substantial part of the genome of the Palmera goat breed comprised short ROH, which suggests a strong and ancient founder effect.ConclusionsAdmixture with African goats, genetic drift and inbreeding have had different effects across the seven Spanish goat breeds analysed in the current work. This has generated distinct patterns of genome-wide diversity that provide new clues about the demographic history of these populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-016-0229-6) contains supplementary material, which is available to authorized users.

This finding may indicate that long-term follow-up might be necessary in these patients. In addition, metastatic radical surgery of SFTs should be considered to achieve long-term survival since there are no currently available effective systemic therapies.

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Background Checkpoint inhibitors (CPI) have drastically improved metastatic cancer outcomes. However, immunotherapy is associated to multiple toxicities, including acute renal injury (AKI). Data about CPI related AKI are limited. Our aim was to determine risk factors for CPI related AKI, as well as its clinical characteristics and its impact on mortality in patients undergoing immunotherapy. Methods All patients under CPI at our center between March 2018 and May 2019, and with a follow up until April 2020, were included. Demographical, clinical data and laboratory results were collected. AKI was defined according to KDIGO guidelines. We performed a logistic regression model to identify independent risk factors for AKI and actuarial survival analysis to establish risk factors for mortality in this population. Results 759 patients were included, with a median age of 64 years. 59% were men and baseline median creatinine was 0.80 mg/dL. Most frequent malignance was lung cancer and 56% were receiving anti-PD1. 15.5% developed AKI during the follow-up. Age and baseline kidney function were identified as independent risk factors for AKI related ICI. At the end of follow-up, 52.3% patients had died. Type of cancer (not melanoma, lung or urogenital malignance), type of CPI (not CTLA4, PD-1, PD-L1 or their combination) and the presence of an episode of AKI were identified as risk factors for mortality. Conclusions 15.5% of patients under immunotherapy presented AKI. A single AKI episode was identified as an independent risk factor for mortality in these patients and age and baseline renal function were risks factors for the development of AKI.

Background Checkpoint inhibitors (CPIs) are used to treat solid organ metastatic malignancies. They act by triggering a vigorous immune response against tumoural cells, preventing their proliferation and metastasis. However, this is not a selective response and can cause immune-related adverse events (irAEs). The kidney can potentially be damaged, with an incidence of irAEs of 1–4%. The most frequent type of toxicity described is acute interstitial nephritis (AIN). Methods We conducted a study of patients with solid organ metastatic malignancies treated with immunotherapy who developed acute renal injury and underwent kidney biopsy in the last 14 months at the Vall d’Hebron University Hospital. Results In all, 826 solid organ malignancies were treated with immunotherapy in our centre, 125 of them (15.1%) developed acute kidney injury (AKI), 23 (18.4% of AKI) visited the nephrology department and 8 underwent kidney biopsy. The most frequent malignancy was lung cancer, in five patients (62%), followed by two patients (25%) with melanoma and one patient (12%) with pancreatic cancer. Four patients (50%) had already received previous oncological therapy, and for the remaining four patients (50%), CPI was the first-line therapy. Five patients (62%) were treated with anti-programmed cell death protein 1, three patients (37%) received anti-programmed death ligand 1 and two (25%) patients were treated in combination with anti-cytotoxic T-lymphocyte antigen 4. The time between the start of CPI and the onset of the AKI ranged from 2 to 11 months. The most frequent urine findings were subnephrotic-range proteinuria, with a mean protein:creatinine ratio of 544 mg/g (standard deviation 147) and eosinophiluria. All patients were biopsied after being diagnosed with AIN. Three patients (37%) received treatment with pulses of methylprednisolone 250–500 mg/day and five patients (62%) received prednisone 1 mg/kg/day. Seven patients (87%) experienced recovery of kidney function and one patient (12%) progressed to chronic kidney disease. Conclusions We report on eight patients with CPI-related AIN diagnosed in the last 14 months at our centre. The novel immunotherapy treatment of metastatic solid organ malignancies carries a higher risk of irAEs. The kidney is one of the most commonly affected organs, frequently presenting as an AIN and exhibiting a favourable response to steroid treatment.