Pericytes in the disease spotlight.

Pericytes are known as the mural cells in small-caliber vessels that interact closely with the endothelium. Pericytes play a key role in vasculature formation and homeostasis, and when dysfunctional contribute to vasculature-related diseases such as diabetic retinopathy and neurodegenerative conditions. In addition, significant extravascular roles of pathological pericytes are being discovered with relevant implications for cancer and fibrosis. Pericyte research is challenged by the lack of consistent molecular markers and clear discrimination criteria versus other (mural) cells. However, advances in single-cell approaches are uncovering and clarifying mural cell identities, biological functions, and ontogeny across organs. We discuss the latest developments in pericyte pathobiology to inform future research directions and potential outcomes.

Molecular detection of hemotropic Mycoplasma and Bartonella species in lice from sheep and goats of Mexico.

The knowledge of lice associated with small ruminants, especially sheep and goats, is scarce. In Mexico, there are historical reports of six species of chewing and sucking lice associated with Capra hircus and Ovis canadensis. However, the reports did not analyze the ecology of the infestations or the presence of potentially pathogenic bacteria. For this reason, the objectives of this study were i) to identify the species of lice associated with sheep and goats in three states of the Mexican Republic, ii) to characterize the infestations, and iii) to identify the presence of bacterial pathogens. From October 2019 to August 2021, six ranches with sheep and goats were sampled in the states of Hidalgo and Veracruz. Hosts were visually inspected, and lice were retrieved with forceps. The specimens were sexed and identified using morphological taxonomic keys. DNA extraction was performed individually, and a fragment of the cytochrome oxidase subunit 1 gene (COI) was amplified for the molecular identification of the specimens. Subsequently, Anaplasma, Bartonella, Ehrlichia, Mycoplasma, and Rickettsia were molecularly detected. Additionally, the infestations were characterized by calculating the prevalence and mean abundances. We collected 563 specimens of three species, Bovicola caprae, Bovicola ovis, and Linognathus africanus. The highest infestation levels were recorded for B. ovis (66.7%; 4.4) from Veracruz. Additionally, two Bartonella species were detected: Bartonella mellophagi in B. ovis and Bartonella capreoli in L. africanus. In contrast, Mycoplasma ovis was detected exclusively in one pool of B. ovis. This study provides new bacterial-ectoparasite associations and highlights the possible role of these neglected ectoparasites as vectors in the populations of sheep and goats from Mexico.

Detection of Bartonella bovis DNA in blood samples from a veterinarian in Mexico

ABSTRACT The genus Bartonella encompasses 38 validated species of Gram-negative, facultative intracellular bacteria that colonize the endothelial cells and erythrocytes of a wide spectrum of mammals. To date, 12 Bartonella species have been recorded infecting humans, causing diseases of long historical characterization, such as cat scratch fever and trench fever, and emerging bartonellosis that mainly affect animal health professionals. For this reason, this study aimed to report a documented case of Bartonella bovis infecting a veterinarian from Mexico by the amplification, sequencing and phylogenetic reconstruction of the citrate synthase (gltA) and the RNA polymerase beta-subunit (rpoB) genes, and to report the natural course of this infection. To our knowledge, this work is the first to report the transmission of B. bovis via needlestick transmission to animal health workers in Latin America.

The genus Rickettsia in Mexico: Current knowledge and perspectives.

The genus Rickettsia encompasses 35 valid species of intracellular, coccobacilli bacteria that can infect several eukaryotic taxa, causing multiple emerging and re-emerging diseases worldwide. This work aimed to gather and summarise the current knowledge about the genus Rickettsia in Mexico, updating the taxonomy of the bacteria and their hosts by including all the records available until 2020, to elucidate host-parasite relationships and determine the geographical distribution of each Rickettsia species present in the country. Until now, 14 species of Rickettsia belonging to four groups have been recorded in Mexico. These species have been associated with 26 arthropod species (14 hard ticks, three soft ticks, two sucking lice, and seven fleas) and 17 mammal species distributed over 30 states in Mexico. This work highlights the high biological inventory of rickettsias for Mexico and reinforces the need to approach the study of this group from a One Health perspective.

Factors that Influence Treatment Delay for Patients with Breast Cancer.

INTRODUCTION: The diagnosis or treatment of breast cancer is sometimes delayed. A lengthy delay may have a negative psychological impact on patients. The aim of our study was to evaluate the sociodemographic, clinical and pathological factors associated with delay in the provision of surgical treatment for localised breast cancer, in a prospective cohort of patients. METHODS: This observational, prospective, multicentre study was conducted in ten hospitals belonging to the Spanish national public health system, located in four Autonomous Communities (regions). The study included 1236 patients, diagnosed through a screening programme or found to be symptomatic, between April 2013 and May 2015. The study variables analysed included each patient's personal history, care situation, tumour history and data on the surgical intervention, pathological anatomy, hospital admission and follow-up. Treatment delay was defined as more than 30 days elapsed between biopsy and surgery. RESULTS: Over half of the study population experienced surgical treatment delay. This delay was greater for patients with no formal education and among widows, persons not requiring assistance for usual activities, those experiencing anxiety or depression, those who had a high BMI or an above-average number of comorbidities, those who were symptomatic, who did not receive NMR spectroscopy, who presented a histology other than infiltrating ductal carcinoma or who had poorly differentiated carcinomas. CONCLUSIONS: Certain sociodemographic and clinical variables are associated with surgical treatment delay. This study identifies factors that influence surgical delays, highlighting the importance of preventing these factors and of raising awareness among the population at risk and among health personnel.

First record of natural infection with Anaplasma marginale in sucking lice infesting the water buffalo (Bubalus bubalis) in Mexico.

The water buffalo (Bubalus bubalis) is an Asian species of bovine which was introduced in Mexico in 1992, as an alternative for milk and meat production. However, little is known about its associated ectoparasites, in particular about their lice. As a part of a project to identify the diversity and prevalence of Anaplasma in cattle and water buffaloes in the state of Veracruz, Mexico, we visited a ranch in the downtown area in which 42 buffaloes were visually inspected for the presence of ectoparasites. Lice were manually recovered, and morphologically identified using taxonomic keys. They were also molecularly identified by the amplification of a fragment of the cytochrome oxidase C subunit I gene (COX1). As a result, we recovered 20 lice from eight animals. All lice were identified as Haematopinus tuberculatus, and the recovered sequences exhibited a similarity of 99.7% with those of the same species deposited in GenBank. Additionally, we detected the presence of Anaplasma marginale in 70% (14/20) of the analysed samples. Our results represent the first record of this exotic ectoparasite for the country.

Acute respiratory failure among lung transplant adults requiring intensive care: Changing spectrum of causative organisms and impact of procalcitonin test in the diagnostic workup.

BACKGROUND: The aim was to identify the causing organisms and assess the association of procalcitonin (PCT) with bacterial pneumonia within 24 hours of intensive care unit admission (ICU-A) among lung transplant (LT) adult recipients. METHODS: Secondary analysis from a prospective cohort study. All LT adults admitted to ICU for acute respiratory failure (ARF) over 5 years were included. Patients were followed until hospital discharge or death. RESULTS: Fifty-eight consecutive LT patients were enrolled. The most important cause of ICU-A due to ARF was pneumonia 29 (50%) followed by acute rejection 3 (5.2%) and bronchiolitis obliterans syndrome exacerbation 3 (5.2%). Microorganisms were isolated from 22/29 cases with pneumonia (75.9%): 17 (77.2%) bacterial, 4 (18.2%) viral, 1 (4.5%) Aspergillus fumigates, with Pseudomonas aeruginosa being the most common cause (45.5%) of pneumonia, with 10 patients presenting chronic colonization by P aeruginosa. Median [Interquartile range (IQR)] PCT levels within 24 hours after admission were higher in pneumonia (1.5 µg/L; IQR:0.3-22.0), than in non-pneumonia cases (0.2 µg/L; IQR:0.1-0.7) (P = .019) and PCT levels within 24 hours helped to discriminate bacterial pneumonia (8.2 µg/L; IQR:0.2-43.0) from viral pneumonia and non-pneumonia cases (0.2 µg/L; IQR:0.1-0.7). The overall negative predictive value for bacterial pneumonia was 85.1%, increasing to 91.6% among episodes after 6 months of LT. CONCLUSIONS: Causes of severe pneumonia in LT are changing, with predominant role of P aeruginosa and respiratory viruses. PCT ≤ 0.5 µg/L within 24 hours helps to exclude bacterial pneumonia diagnosis in LT adults requiring ICU-A. A negative PCT test allows antimicrobial de-escalation and requires an alternative diagnostic to bacterial pneumonia.

Phosphoinositide 3-Kinase-Regulated Pericyte Maturation Governs Vascular Remodeling.

BACKGROUND: Pericytes regulate vessel stabilization and function, and their loss is associated with diseases such as diabetic retinopathy or cancer. Despite their physiological importance, pericyte function and molecular regulation during angiogenesis remain poorly understood. METHODS: To decipher the transcriptomic programs of pericytes during angiogenesis, we crossed Pdgfrb(BAC)-CreERT2 mice into RiboTagflox/flox mice. Pericyte morphological changes were assessed in mural cell-specific R26-mTmG reporter mice, in which low doses of tamoxifen allowed labeling of single-cell pericytes at high resolution. To study the role of phosphoinositide 3-kinase (PI3K) signaling in pericyte biology during angiogenesis, we used genetic mouse models that allow selective inactivation of PI3Kα and PI3Kß isoforms and their negative regulator phosphate and tensin homolog deleted on chromosome 10 (PTEN) in mural cells. RESULTS: At the onset of angiogenesis, pericytes exhibit molecular traits of cell proliferation and activated PI3K signaling, whereas during vascular remodeling, pericytes upregulate genes involved in mature pericyte cell function, together with a remarkable decrease in PI3K signaling. Immature pericytes showed stellate shape and high proliferation, and mature pericytes were quiescent and elongated. Unexpectedly, we demonstrate that PI3Kß, but not PI3Kα, regulates pericyte proliferation and maturation during vessel formation. Genetic PI3Kß inactivation in pericytes triggered early pericyte maturation. Conversely, unleashing PI3K signaling by means of PTEN deletion delayed pericyte maturation. Pericyte maturation was necessary to undergo vessel remodeling during angiogenesis. CONCLUSIONS: Our results identify new molecular and morphological traits associated with pericyte maturation and uncover PI3Kß activity as a checkpoint to ensure appropriate vessel formation. In turn, our results may open new therapeutic opportunities to regulate angiogenesis in pathological processes through the manipulation of pericyte PI3Kß activity.

Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer.

Gene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkb1 alone in the murine prostate epithelium was inconsequential for tumorigenesis, its combination with an oncogenic insult, illustrated by Pten heterozygosity, elicited lethal metastatic prostate cancer. Despite the low frequency of LKB1 deletion in patients, this event was significantly enriched in lung metastasis. Modeling the role of LKB1 in cellular systems revealed that the residual activity retained in a reported kinase-dead form, LKB1K78I, was sufficient to hamper tumor aggressiveness and metastatic dissemination. Our data suggest that prostate cells can function normally with low activity of LKB1, whereas its complete absence influences prostate cancer pathogenesis and dissemination.

Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer.

OBJECTIVES: Tumor associated fibroblasts (TAFs) are essential contributors of the progression of non-small cell lung cancer (NSCLC). Most lung TAFs exhibit an activated phenotype characterized by the expression of α-SMA and fibrillar collagens. However, the prognostic value of these activation markers in NSCLC remains unclear. MATERIAL AND METHODS: We conducted a quantitative image analysis of α-SMA immunostaining and picrosirius red staining of fibrillar collagens imaged by bright-field and polarized microscopy, respectively, using tissue microarrays with samples from 220 surgical patients, which elicited a percentage of positive staining area for each marker and patient. RESULTS: Kaplan-Meier curves showed that all TAF activation markers were significantly associated with poor survival, and their prognostic value was independent of TNM staging as revealed by multivariate analysis, which elicited an adjusted increased risk of death after 3 years of 129% and 94% for fibrillar collagens imaged with bright-field (p = 0.004) and polarized light (p = 0.003), respectively, and of 89% for α-SMA (p = 0.009). We also found a significant association between all TAF activation markers and tumor necrosis, which is often indicative of hypoxia, supporting a pathologic link between tumor desmoplasia and necrosis/hypoxia. CONCLUSIONS: Our findings identify patients with large histologic coverage of fibrillar collagens and α-SMA + TAFs to be at higher risk of recurrence and death, supporting that they could be considered for adjuvant therapy.

External validation of the PREDICT tool in Spanish women with breast cancer participating in population-based screening programmes.

RATIONALE, AIMS, AND OBJECTIVES: To externally validate the PREDICT tool in a cohort of women participating in a population-based breast cancer screening programme who were diagnosed with breast cancer between 2000 and 2008 in Spain. METHODS: A total of 535 women were included in the validation study. We calculated predicted 5-year survival using the beta values from the development of the PREDICT model and predicted and observed events for a given risk groups. Model fit, discrimination, and calibration were evaluated. Seeking to improve the model, we also explored the impact on discrimination of the inclusion of additional variables, not in the PREDICT algorithm. RESULTS: In patients who were oestrogen receptor (ER) positive (negative), PREDICT overestimated (underestimated) the 5-year overall survival in all the subgroups studied. Analysis of model performance showed good calibration but modest discrimination (C-index, 0.697 [ER negative] and 0.768 [ER positive]). When updating the model, no additional variables were found to be significant in ER-negative patients, but for ER-positive patients, concurrent liver disease was a significant factor, its inclusion improving model discrimination (C-index, 0.817). CONCLUSIONS: The PREDICT tool does not discriminate well in our population considering only the variables of the original algorithm. More accurate tools are needed to obtain a better discrimination.

Tumor-associated metabolic and inflammatory responses in early stage non-small cell lung cancer: Local patterns and prognostic significance.

INTRODUCTION: Non-small cell lung cancer (NSCLC) patients diagnosed in early stage and surgically-treated have five-year mortality rate >20%. The identification of biomarkers able to predict progression and death may help to identify patients needing closer follow-up. METHODS: A retrospective cohort of early-stage surgically-treated NSCLC patients enrolled in the International Association for the Study of Lung Cancer (IASLC) Staging Project was created, and tissue Microarrays (TMAs) were constructed with tumor and non-tumor lung tissue. Pentose phosphate pathway (PPP) proteins (transketolase [TKT] and transketolase-like 1 [TKTL1]), inflammatory markers (cyclooxygenase-2 [COX-2], tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL1ß], nuclear factor kappa-light-chain-enhancer of activated B cells [NFκB]-p65 and antigen Ki-67), and programmed death-ligand 1 (PDL1) were measured by immunohistochemistry. RESULTS: NSCLC patients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) were included in the study (n = 199). TKT and TKTL1 were significantly higher in ADC than in non-tumor tissue (p < 0.001). Higher values were also observed in NSCLC for all the inflammatory markers, with figures >30% above those of non-tumor tissue (p < 0.001). PDL1 analysis showed a higher percentage of positivity in ADC than in non-tumor tissue (p < 0.001). Multivariate Cox proportional hazards modeling confirmed that high IL1ß level in tumor tissue was independently associated with 3-year mortality in NSCLC [HR = 2.05, 95% CI (1.1-3.7), p = 0.019], a relationship driven by ADC subtype. CONCLUSION: This study confirms an increase in metabolic activity and an inflammatory response in tumor tissue of early stage NSCLC, and a significant relationship between high levels of IL1ß in the tumor and poor prognosis in ADC.

Clinical and histologic characteristics of breast cancers in women with previous pathologic diagnosis of benign breast disease in Spain.

Women with a benign breast disease (BBD) have an increased risk of subsequent breast carcinoma. Information is scarce regarding the characteristics of breast carcinomas diagnosed after a BBD. Our aim was to point out the differences in clinical and histologic characteristics of breast carcinomas diagnosed in women with and without a previous pathologic diagnosis of BBD in the context of population-based mammography screening. Retrospective cohort study of all women aged 50-69 years who were screened at least once in a population-based screening program in Spain, between 1994 and 2011 and followed up until December 2012. The mean follow-up was 6.1 years. We analyzed 6645 breast carcinomas, of whom 238 had a previous pathologic diagnosis of BBD. Information on clinical and histologic characteristics was collected from pathology reports. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (95%CI) of occurrence of selected histologic characteristics of breast carcinomas in women with and without a previous BBD. Women with a previous BBD had a higher proportion of ductal carcinoma in situ (DCIS) compared with women without a BBD (22.1% and 13.6%, respectively). Among those diagnosed with an invasive breast carcinoma, women with previous BBD were more likely to be diagnosed with carcinomas sized >2 cm (OR = 1.46; 95%CI = 1.03-2.08), metastatic positive (OR = 2.66; 95%CI = 1.21-5.86), and with a high Ki-67 proliferation rate (OR = 1.93; 95%CI = 1.24-2.99). No differences were found across histologic subtypes of BBD. Screening participants with a previous pathologic diagnosis of BBD had a higher proportion of DCIS. However, invasive carcinomas detected in women with a BBD were associated with clinical and histologic characteristics conferring a worst prognosis.

The effect of information about the benefits and harms of mammography on women's decision-making: study protocol for a randomized controlled trial.

BACKGROUND: The decision to participate or not in breast cancer screening is complex due to the trade-off between the expected benefit of breast cancer mortality reduction and the major harm of overdiagnosis. It seems ethically necessary to inform women so that they can actively participate in decision-making and make an informed choice based on their values and preferences. The objective of this study is to assess the effects of receiving information about the benefits and harms of screening on decision-making, in women approaching the age of invitation to mammography screening. METHODS: A two-stage, randomized controlled trial (RCT). In the first stage, 40 Basic Health Areas (BHAs) will be selected and randomized to intervention or control. In the second stage, women within each BHA will be randomly selected (n = 400). Four breast cancer screening programs (BCSPs) of the Spanish public health system, three in Catalonia and one in the Canary Islands will participate in the study. Women in the intervention arm will receive a leaflet with detailed information on the benefits and harms of screening using mammography. Women in the control arm will receive a standard leaflet that does not mention harms and recommends accepting the invitation to participate in the biennial examinations of the BCSP. The primary outcome is informed choice, a dichotomous variable that combines knowledge, attitudes, and intentions. Secondary outcomes include decisional conflict; confidence in the decision made; anxiety about screening participation; worry about breast cancer; anticipated regret; time perspective; perceived importance of benefits/harms of screening; perceived risk of breast cancer; and leaflet acceptability. Primary and secondary outcomes are assessed 2-3 weeks after the intervention. DISCUSSION: This is the first RCT that assesses the effect of informing about the benefits and harms of breast cancer screening in Spain in women facing the decision to be screened using mammography. It aims to assess the impact of information on several decisional outcomes and to contribute to paving the road towards shared decision-making in breast cancer screening in our country. TRIAL REGISTRATION: ClinicalTrials.gov registry, ID: NCT03046004 . Retrospectively registered on 4 February 2017. Trial name: InforMa study.

Biomarkers expression in benign breast diseases and risk of subsequent breast cancer: a case-control study.

Women with benign breast diseases (BBD) have a high risk of breast cancer. However, no biomarkers have been clearly established to predict cancer in these women. Our aim was to explore whether estrogen receptor (ER), progesterone receptor (PR), and Ki67 expression stratify risk of breast cancer in screened women with BBD. We conducted a nested case-control study. Women with breast cancer and prior BBDs (86 cases) were matched to women with prior BBDs who were free from breast cancer (172 controls). The matching factors were age at BBD diagnosis, type of BBD, and follow-up time since BBD diagnosis. ER, PR, and Ki67 expression were obtained from BBDs' specimens. Conditional logistic regression was used to estimate odds ratios (ORs), and 95% confidence intervals (CIs) of breast cancer risk according to ER, PR, and Ki67 expression. Women with >90% of ER expression had a higher risk of breast cancer (OR = 2.63; 95% CI: 1.26-5.51) than women with ≤70% of ER expression. Similarly, women with >80% of PR expression had a higher risk of breast cancer (OR = 2.22; 95% CI: 1.15-4.27) than women with ≤40% of PR expression. Women with proliferative disease and ≥1% of Ki67 expression had a nonsignificantly increased risk of breast cancer (OR = 1.16; 95% CI: 0.46-2.90) than women with <1% of Ki67 expression. A high expression of ER and PR in BBD is associated with an increased risk of subsequent breast cancer. In proliferative disease, high Ki67 expression may also have an increased risk. This information is helpful to better characterize BBD and is one more step toward personalizing the clinical management of these women.

Prevalence of persistent pain after breast cancer treatment by detection mode among participants in population-based screening programs.

BACKGROUND: To date, the study of the risks and benefits of breast cancer screening has not included the onset of persistent pain after breast cancer treatment within the context of population-based screening programs. Our purpose was to investigate the prevalence of persistent pain and associated factors in women diagnosed with breast cancer (screening or interval) in the context of a population-based breast cancer screening program in Spain. METHODS: A total of 1,057 women participating in a population-based breast cancer screening program were diagnosed with breast cancer between 2000 and 2008. The women were treated surgically and followed-up to 2013. The risk of developing persistent pain was estimated through multivariate logistic regression analysis. RESULTS: Breast cancer was detected during routine screening in 732 women (69.3 %) and emerged as an interval cancer between two screening rounds in 325 (30.7 %). Persistent pain was present in 118 women (11.3 %). Women diagnosed through routine screening reported a higher prevalence of persistent pain (12.9 %) than those with interval cancers (7.8 %)(P < 0.05). Multivariate logistic regression analysis identified two other variables associated with persistent pain: having a Charlson index > =2 (Odds Ratio [OR]: 4.5 95 % Confidence Interval [CI]: 2.1-9.5) versus no comorbidities, and having undergone an axillary lymph node dissection (OR: 2.0 95 % CI: 1.0-4.0) versus sentinel lymph node biopsy. CONCLUSIONS: The prevalence of persistent pain was relatively low. The detection mode was not related to the onset of persistent pain. The factors associated with persistent pain were a Charlson index > =2 and the performance of axillary lymph node dissection. Women treated for breast cancer are at risk for developing persistent pain regardless of the detection mode, especially those with comorbidities and those who have undergone axillary lymph node dissection.

Clinical and radiological features of breast tumors according to history of false-positive results in mammography screening.

BACKGROUND: Women with a false-positive result after a screening mammogram have an increased risk of cancer detection in subsequent participations, especially after assessments involving cytology or biopsy. We aimed to compare women's personal characteristics, tumoral features and the radiological appearance of cancers with and without a previous false-positive result generated by additional imaging or invasive procedures. METHODS: From 1996 to 2007, 111,098 women aged 45-69 years participated in four population-based breast cancer screening programs in Spain, and 1281 cancers were detected. We included all cancers detected in subsequent screenings (n=703) and explored the occurrence of previous false-positive results. We identified false-positives requiring additional imaging or invasive procedures. Differences on tumoral features (invasiveness, tumor size, and lymph node status) and radiological appearance were assessed by Chi-square test, and agreement between the location of cancer and prior suspicious by Cohen's kappa coefficient. A multivariate analysis was preformed to evaluate the effect of previous screening results and age on the odds of presenting an in situ carcinoma. RESULTS: Among the 703 cancers detected in subsequent screenings, 148 women (21.1%) had a previous false-positive result. Of these, 105 were by additional imaging and 43 by invasive procedures. Women with prior false-positive result requiring invasive assessment, compared to women with negative tests, and women with prior false-positive requiring additional imaging, had a higher proportion of in situ carcinomas (31.7%, 15.3%, 12.9%, respectively; p=0.014) and microcalcifications (37.2%, 20.2%, 9.5%, respectively; p=0.003). The proportion of in situ carcinomas was even higher in women over 60 years (39.2%, 12.5%, 13.0%, respectively; p=0.001). Ipsilateral cancer was observed in 65.7% of cases with prior cytology or biopsy (k=0.479; 95%CI: 0.330-0.794). CONCLUSION: A large number of in situ malignancies and calcification patterns were found among women with prior false-positive result in mammography screening requiring cytology or biopsies, suggesting progression from a previously benign lesion.

Differences in radiological patterns, tumour characteristics and diagnostic precision between digital mammography and screen-film mammography in four breast cancer screening programmes in Spain.

OBJECTIVES: To compare tumour characteristics between cancers detected with screen-film mammography (SFM) and digital mammography (DM) and to evaluate changes in positive predictive values (PPVs) for further assessments, for invasive procedures and for distinct radiological patterns in recalled women. METHODS: 242,838 screening mammograms (171,191 SFM and 71,647 DM) from 103,613 women aged 45-69 years, performed in four population-based breast cancer screening programmes in Spain, were included. The tumour characteristics and PPVs of each group were compared. Radiological patterns (masses, calcifications, distortions and asymmetries) among recalled women were described and PPVs were evaluated. RESULTS: The percentages of ductal carcinoma in situ (DCIS) were higher in DM than in SFM both in the first [18.5% vs. 15.8%(p = 0.580)] and in successive screenings [23.2% vs. 15.7%(p = 0.115)]. PPVs for masses, asymmetries and calcifications were higher in DM, being statistically significant in masses (5.3% vs. 3.9%; proportion ratio: 1.37 95%CI: 1.08-1.72). Among cancers detected by calcifications, the percentage of DCIS was higher in DM (60.3% vs. 46.4%, p = 0.060). CONCLUSIONS: PPVs were higher when DM was used, both for further assessments and for invasive procedures, with similar cancer detection rates and no statistically significant differences in tumour characteristics. The greatest improvements in PPVs were found for masses.