Real-world effectiveness of ribociclib in metastatic breast cancer patients: Does dose affect survival?

Introduction: Real-world data are critical to demonstrate the reproducibility of evidence and external generalizability of randomized clinical trials. The purpose of this study was to assess real-world security profile and management of adverse events (AEs) presented with ribociclib for the treatment of HR + /HER2- metastatic breast cancer (MBC). Our secondary objective was to provide real-world effectiveness of this treatment (measured with progression-free survival (PFS)) and to confirm the hypothesis that dose reductions are not related with disease progression. Material and methods: Observational retrospective study evaluating all females with MBC treated with ribociclib. Study period: January 2017 to September 2019. Follow-up was done until November 2021. Response was assessed through the PFS according to RECIST1.1 and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) was used to classify AEs. Results: The most common AE was any grade neutropenia, documented in 37 of 53 patients (69.8%) during the course of treatment. By the end of the follow-up period, overall median PFS with ribociclib therapy was 27.3 months (95% confidence interval (CI) 20.8-71.8 months). In total, 50 patients (94.4%) initiated ribociclib at 600 mg dose, 28 patients (58%) required dose reductions. PFS of patients receiving ribociclib as first-line treatment was 28 (95% CI 15-41 months). Conclusions: Our results from patients treated in real-world clinical settings indicate that ribociclib is safe and their AEs are manageable with active monitoring, temporal suspension of treatment and dose reduction. Furthermore, our results indicate that dose reduction of ribociclib is not associated with a loss of efficacy.

An Agave Counting Methodology Based on Mathematical Morphology and Images Acquired through Unmanned Aerial Vehicles.

Blue agave is an important commercial crop in Mexico, and it is the main source of the traditional mexican beverage known as tequila. The variety of blue agave crop known as Tequilana Weber is a crucial element for tequila agribusiness and the agricultural economy in Mexico. The number of agave plants in the field is one of the main parameters for estimating production of tequila. In this manuscript, we describe a mathematical morphology-based algorithm that addresses the agave automatic counting task. The proposed methodology was applied to a set of real images collected using an Unmanned Aerial Vehicle equipped with a digital Red-Green-Blue (RGB) camera. The number of plants automatically identified in the collected images was compared to the number of plants counted by hand. Accuracy of the proposed algorithm depended on the size heterogeneity of plants in the field and illumination. Accuracy ranged from 0.8309 to 0.9806, and performance of the proposed algorithm was satisfactory.

Prospective, study comparing the accuracy of two different stool antigen tests (Premier Platinum HpSA and novel ImmunoCard STAT! rapid test) for the diagnosis of Helicobacter pylori infection.

BACKGROUND: At present only monoclonal EIA (enzyme-immunoassay) stool antigen-tests have obtained optimal accuracy in the diagnosis of Helicobacter pylori. Our aim was to evaluate the accuracy of two stool antigen-tests, the validated Premier Platinum HpSA PLUS (EIA test) and the newly available ImmunoCard STAT! HpSA HD (rapid test) for the initial diagnosis and the confirmation of eradication of H. pylori infection. PATIENTS AND METHODS: Patients with indication of H. pylori diagnosis, or confirmation after treatment were included. Data were coded to protect personal data and ensure blindness between tests. Accuracy was considered as coincident diagnosis with the gold standard (13C-urea breath test, UBT). The EIA was used as a bench standard. All stool tests were performed in duplicate. RESULTS: 264 patients completed the protocol (100 naïve, 164 post-eradication). Average age was 52 years, 61% women, 11% ulcer. Positive diagnoses by UBT were 41% for naïve and 17% for post-eradication. Overall ImmunoCard and EIA accuracies were respectively 91% (95%C.I.=88-94%) and 89% (86-93%), sensitivities 72% (67-78%) and 72% (67-78%), and specificities 98% (96-100%), and 95% (92-97%). Concordance between ImmunoCard and EIA was 95% (93-98%). DISCUSSION: Our results indicate that the newly available ImmunoCard rapid stool antigen-test achieves 90% accuracy, with high specificity but suboptimal sensitivity. The ImmunoCard attained equivalent accuracies as the EIA bench standard, with 95% concordance.

Impact of the Microbiota and Gastric Disease Development by Helicobacter pylori.

Microorganisms in humans form complex communities with important functions and differences in each part of the body. The stomach was considered to be a sterile organ until the discovery of Helicobacter pylori, but nowadays, it is possible to demonstrate that other microorganisms beyond H. pylori can colonize the gastric mucosa and that the diverse microbiota ecosystem of the stomach is different from the mouth and the esophagus, and also from the small intestine and large intestine. H. pylori seems to be the most important member of the gastric microbiota with the highest relative abundance when present, but when it is absent, the stomach has a diverse microbiota. Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria are the most abundant phyla in both H. pylori-positive and H. pylori-negative patients. The gastric commensal flora may play some role in the H. pylori-associated carcinogenicity, and differences in the gastric microbiota composition of patients with gastric cancer, intestinal metaplasia, and chronic gastritis are described. The gastric microbiota changed gradually from non-atrophic gastritis to intestinal metaplasia, and to gastric cancer (type intestinal).

Avoiding Small Intestinal Biopsies for Diagnosis of Celiac Disease in Children: A Reliable Strategy for All Patients?

BACKGROUND: Current reports applying ESPGHAN exception criteria (EEC) to diagnose celiac disease (CD) without duodenal biopsies indicate that a high percentage of patients with CD may be identified when applied correctly in specialized settings. Application of the EEC, however, in "daily life conditions" at the different levels of medical services is not clear. METHODS: EEC was applied to 130 pediatric patients evaluated for CD at 5 public hospitals in Santiago, Chile, during 2010 to 2015. Clinical presentation, serum anti-tissue transglutaminase 2 and anti-endomysium antibodies (EMA), genotyping, and small intestinal histology were obtained from clinical charts. RESULTS: A total of 78 of 130 patients reviewed had some of the data required for analysis, but EMA was determined in 54% and genotyping in 2.3% of patients, limiting the study. After offering free genotyping, only 12 of 78 (15%) had all data required for EEC application. In this small group, 10 of 12 (83.3%) patients could avoid duodenal biopsies and 2 (16.7%) with potential CD were misdiagnosed. Main reasons for not doing EMA and genotyping were that they are expensive, unavailable in the local health care center, and considered "not necessary" for diagnosis. CONCLUSION: Limited resources in clinical settings reduce availability of EMA and genotyping, making application of EEC criteria difficult and only possible only in 15% of our patients. Within this subgroup, biopsies could be avoided in 83.3%, and 16.7% of patients with potential CD were misdiagnosed. Insufficient studies and incorrect interpretation of EEC contributed to incomplete assessment in 52 of 130 (40%) patients. The Chilean public health system is likely representative of several others present in developing and developed countries.

Helicobacter pylori treatment: antibiotics or probiotics.

Treatment of Helicobacter pylori infection is important for the management of gastrointestinal disorders such as peptic ulcer and gastric cancer. Due to the increase in the prevalence of H. pylori resistance to antibiotics, triple therapy with clarithromycin is no longer the best treatment for H. pylori, especially in some areas where the local resistance to this antibiotic is higher than 20%. Alternative treatments have been proposed for the eradication of H. pylori. Some of them including novel antibiotics or classical ones in different combinations; these treatments are being used in the regular clinical practice as novel and more effective treatments. Others therapies are using probiotics associated to antibiotics to treat this infection.The present article is a revision of H. pylori eradication treatment, focusing on emerging approaches to avoid the treatment failure, using new therapies with antimicrobials or with probiotics.

Antibiotic resistance in Helicobacter pylori.

PURPOSE OF REVIEW: Treatment of Helicobacter pylori is difficult nowadays because of its high resistance. The prevalence and mechanism of resistance, the different methods to detect it and the clinical implication of resistance were addressed in several research papers last year. RECENT FINDINGS: Clarithromycin-resistant H. pylori has been recognized by the WHO as 'high priority', for which new antibiotics are needed. Moreover, the Maastricht consensus recommended, in areas with high resistance, that susceptibility tests should be performed, at least after a treatment failure. SUMMARY: Metronidazole and clarithromycin resistance rates are alarming although they vary among populations. Tetracycline and amoxicillin-resistance are very low in most countries. H. pylori resistance can be detected by phenotypic or by molecular methods. Different break points may be used when performing an antimicrobial susceptibility test, so comparing resistance among different populations is challenging. Genomic techniques open new possibilities in the diagnosis of H. pylori, and the detection of H. pylori and its antimicrobial resistance in faeces is an interesting approach. Eradication rates are dependent on the susceptibility of the strain to metronidazole and clarithromycin, being lower in patients infected with a resistant strain.

Comprehensive geriatric assessment for identifying older people at risk of hip fracture: cross-sectional study with comparative group.

Background: Hip fracture (HF) is by far the most common serious fragility fracture. Its care is a major challenge to all healthcare systems. Aim: To determine whether there are characteristics of older people identified via comprehensive geriatric assessment (CGA) that help identify those with an increased risk of HF. Methods: The demographic, functional, cognitive and nutritional data of a cohort of patients admitted for acute HF were compared with those of a population cohort representing community-dwelling older people in the same urban district without HF. Bivariate analysis was performed on the variables in both the complete samples and in a subsample of age and sex paired subjects, followed by logistic regression analysis. Results: A total of 509 HF patients and 1315 community-dwelling older people were included. The HF patients were older and more frequently women and had more frequent disability and cognitive impairment, lower handgrip strength, lower body mass index (BMI) and a higher frequency of vitamin D deficiency compared with the community controls (P < 0.001). The variables most strongly associated with the presence of HF in the multivariate analysis, aside from age and female sex, were BMI<22 kg/m2 [odds ratio (OR) = 5.11], disability (OR = 4.32), muscle weakness (OR = 3.01), and vitamin D deficiency (OR = 2.13). Conclusions: There are easily obtained CGA determinants that are strongly associated with fragility HF. The detection of low weight, disability, malnutrition, muscle weakness, and vitamin D deficiency can help identify at-risk older people to implement prevention strategies.

Antimicrobial susceptibility of 6 antimicrobial agents in Helicobacter pylori clinical isolates by using EUCAST breakpoints compared with previously used breakpoints.

INTRODUCTION: The aim of this study was to determine the differences in percentage resistance in H. pylori clinical isolates using EUCAST breakpoints compared with previously used breakpoints. MIC value distribution in H. pylori clinical isolates was also studied. METHODS: Susceptibility to amoxicillin, tetracycline, metronidazole, clarithromycin, rifampicin and levofloxacin was performed by E-test in 824 H. pylori clinical isolates. EUCAST and previous breakpoints defined resistance as follows: MIC >0.12mg/L and ≥2mg/L for amoxicillin, >8mg/L and ≥8mg/L for metronidazole, >0.5mg/L and ≥1mg/L for clarithromycin, >1mg/L and ≥32mg/L for rifampicin, and >1mg/L and ≥4mg/L for tetracycline and >1mg/L levofloxacin. RESULTS: Overall resistance rate by EUCAST and by previous breakpoints was 8.5% and 3.2% for amoxicillin, 0.6% and 0.1% for tetracycline, 39.2% and 39.7% for metronidazole, 51.2% and 51.2% for clarithromycin, 32% and 3.1% for rifampicin, and 6.7% and 6.7% for levofloxacin. CONCLUSIONS: When using the different breakpoints for antimicrobial susceptibility testing, similar results were found with most antibiotics tested (tetracycline, metronidazole, clarithromycin, and levofloxacin), except for amoxicillin and rifampicin.

A Multi-Disciplinary Approach to Remote Sensing through Low-Cost UAVs.

The use of Unmanned Aerial Vehicles (UAVs) based on remote sensing has generated low cost monitoring, since the data can be acquired quickly and easily. This paper reports the experience related to agave crop analysis with a low cost UAV. The data were processed by traditional photogrammetric flow and data extraction techniques were applied to extract new layers and separate the agave plants from weeds and other elements of the environment. Our proposal combines elements of photogrammetry, computer vision, data mining, geomatics and computer science. This fusion leads to very interesting results in agave control. This paper aims to demonstrate the potential of UAV monitoring in agave crops and the importance of information processing with reliable data flow.

Crop Classification in Satellite Images through Probabilistic Segmentation Based on Multiple Sources.

Classification methods based on Gaussian Markov Measure Field Models and other probabilistic approaches have to face the problem of construction of the likelihood. Typically, in these methods, the likelihood is computed from 1D or 3D histograms. However, when the number of information sources grows, as in the case of satellite images, the histogram construction becomes more difficult due to the high dimensionality of the feature space. In this work, we propose a generalization of Gaussian Markov Measure Field Models and provide a probabilistic segmentation scheme, which fuses multiple information sources for image segmentation. In particular, we apply the general model to classify types of crops in satellite images. The proposed method allows us to combine several feature spaces. For this purpose, the method requires prior information for building a 3D histogram for each considered feature space. Based on previous histograms, we can compute the likelihood of each site of the image to belong to a class. The computed likelihoods are the main input of the proposed algorithm and are combined in the proposed model using a contrast criteria. Different feature spaces are analyzed, among them are 6 spectral bands from LANDSAT 5 TM, 3 principal components from PCA on 6 spectral bands and 3 principal components from PCA applied on 10 vegetation indices. The proposed algorithm was applied to a real image and obtained excellent results in comparison to different classification algorithms used in crop classification.

Phylogeographic evidence of cognate recognition site patterns and transformation efficiency differences in H. pylori: theory of strain dominance.

BACKGROUND: Helicobacter pylori has diverged in parallel to its human host, leading to distinct phylogeographic populations. Recent evidence suggests that in the current human mixing in Latin America, European H. pylori (hpEurope) are increasingly dominant at the expense of Amerindian haplotypes (hspAmerind). This phenomenon might occur via DNA recombination, modulated by restriction-modification systems (RMS), in which differences in cognate recognition sites (CRS) and in active methylases will determine direction and frequency of gene flow. We hypothesized that genomes from hspAmerind strains that evolved from a small founder population have lost CRS for RMS and active methylases, promoting hpEurope's DNA invasion. We determined the observed and expected frequencies of CRS for RMS in DNA from 7 H. pylori whole genomes and 110 multilocus sequences. We also measured the number of active methylases by resistance to in vitro digestion by 16 restriction enzymes of genomic DNA from 9 hpEurope and 9 hspAmerind strains, and determined the direction of DNA uptake in co-culture experiments of hspAmerind and hpEurope strains. RESULTS: Most of the CRS were underrepresented with consistency between whole genomes and multilocus sequences. Although neither the frequency of CRS nor the number of active methylases differ among the bacterial populations (average 8.6 ± 2.6), hspAmerind strains had a restriction profile distinct from that in hpEurope strains, with 15 recognition sites accounting for the differences. Amerindians strains also exhibited higher transformation rates than European strains, and were more susceptible to be subverted by larger DNA hpEurope-fragments than vice versa. CONCLUSIONS: The geographical variation in the pattern of CRS provides evidence for ancestral differences in RMS representation and function, and the transformation findings support the hypothesis of Europeanization of the Amerindian strains in Latin America via DNA recombination.

Helicobacter pylori in pediatrics.

This review concerned the important pediatric studies published between April 2012 and March 2013. Symptomatology in Helicobacter pylori-positive children is nonspecific, except for those suffering from peptic ulcer diseases. Investigation of H. pylori status in children and adolescents with sideropenic anemia is recommended, and it is the aim of several studies worldwide. Associations of H. pylori with plasma ghrelin levels as well as the negative association of H. pylori with atopic disease were interesting objectives for several studies this year. Success rates of sequential therapy tended to be lower in recent studies than in previous trials, which probably reflects the increase in macrolide resistance. A beneficial effect of probiotics was reported although not all trials supported this result in children. Intrafamilial transmission and young age could be major risk factors associated with reinfection in children.

Whole Genome Sequencing for Studying Helicobacter pylori Antimicrobial Resistance.

Antibiotic resistance (AMR) is an alarming concern worldwide and Helicobacter pylori, one of the most prevalent bacteria, is not an exception. With antibiotics being its primary therapy, increasing resistance leads to a higher rate of treatment failure. Understanding the genomic mechanisms of resistance to clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline, and rifampicin through next-generation sequencing-based molecular tools, such as whole genome sequencing (WGS), can be of great value, not only to direct a patient's treatment, but also to establish and optimize treatment guidelines according to the local epidemiology and to avoid the use of inappropriate antibiotics. WGS approaches allow us to gain insight into the genomic determinants involved in AMR. To this end, different pipelines and platforms are continuously being developed. In this study, we take a more detailed view of the use and progression of WGS for in-depth study of H. pylori's AMR.

Are molecular methods helpful for the diagnosis of Helicobacter pylori infection and for the prediction of its antimicrobial resistance?

Infections produced by Helicobacter pylori (H. pylori), a spiral Gram-negative bacterium, can cause chronic gastritis, peptic ulcer, and gastric cancer. Antibiotic therapy is the most effective treatment for H. pylori infection at present. However, owing to the increasing antibiotic resistance of H. pylori strains, it has become a serious threat to human health. Therefore, the accurate diagnosis of H. pylori infections and its antibiotic resistance markers is of great significance. Conventional microbiological diagnosis of H. pylori is based on culture; however, successful isolation of H. pylori from gastric biopsy specimens is a challenging task affected by several factors and has limitations in terms of the time of response. To improve conventional methods, some molecular techniques, such as PCR, have been recently used in both invasive and non-invasive H. pylori diagnosis, enabling simultaneous detection of H. pylori and point mutations responsible for frequent antibiotic resistance. The advantages and disadvantages of molecular methods, mainly PCR, versus conventional culture for the H. pylori identification and the detection of antibiotic resistance are discussed. As expected, the combination of both diagnostic methods will lead to the most efficient identification of the H. pylori strains and the resistance patterns.

Profile and 3-month evolution of geriatric patients after a hip fracture followed-up at a Fracture Liaison Service (FLS).

INTRODUCTION: There are few studies on Fracture Liaison Service (FLS) that evaluate older patients after a hip fracture (HF) through comprehensive geriatric assessment. We aim to determine these patients' characteristics, outcomes, and prescribed treatments. METHODS: A retrospective observational study of a cohort of patients older than 65 years admitted with HFs to an orthogeriatric unit between February 25th (2013) and December 16th (2016). After hospitalization, those patients with a good baseline social, functional, and cognitive situation were referred to the FLS. A comprehensive geriatric assessment and treatment adjustment were conducted. A comparison between FLS patients and HF patients non-referred was made. RESULTS: From 1887 patients admitted to the orthogeriatric unit, 469 (23%) were referred to the FLS. Of those, 335 were women (77.2%) and 337 (77.6%) lived in the community. The FLS patients had a better functional status (97.1% of the patients with independent gait versus 79.2%) than non-FLS patients (p<0.001). After 3 months in the FLS, 356 (82%) patients had independent gait and had improved their analytical values. Antiosteoporotic treatment was prescribed to 322 patients (74%), vitamin D supplements to 397 (91.5%), calcium to 321 (74%), and physical exercise to 421 (97%). CONCLUSIONS: Patients referred to an FLS were younger, with a better functional and cognitive situation. At hospital discharge, they frequently presented gait impairment and laboratory abnormalities (anemia, hypoproteinemia, vitamin D deficiency) that presented good recovery due to the patient's previous baseline. These patients benefit from comprehensive treatment (pharmacological and non-pharmacological).

Prehabilitation and perioperative geriatric care in patients aged over 80 years with colorectal cancer: Results of a cross-speciality geriatrics program.

OBJECTIVES: To describe a perioperative cross-speciality geriatrics program for patients aged >80 years with colorectal cancer (CRC), aimed to detect and manage frailty and to understand its influence on clinical outcomes. MATERIALS AND METHODS: Patients aged >80 years with CRC and proposed for surgery were included from October 2018 to March 2020. Comprehensive geriatric assessments (CGA) were performed. Patients were classified according to the estimated physiological reserve, from fit, frail patients and even the disabled: CGA-1, CGA-2, CGA-3, and CGA-4. Individualised treatment was adapted to each patient's situation. Patients who underwent surgery were followed up by a geriatrician. The presence of complications, length of stay, hospital readmissions at 30 days, and short- and long-term mortality were recorded. RESULTS: Seventy-four patients were included. The mean age was 84.5 ± 4.5 years. 55.4% patients were classified as CGA-1, 24.3% as CGA-2, 16.2% as CGA-3, and 4.1% as CGA-4. No CGA-4 patient was operated on. Frail (CGA-2 and CGA-3) patients had higher medical complications (50% vs 21.2%, p < 0.05) and delirium (30% vs 9.1%, p < 0.05) than fit patients (CGA-1). They also had higher rates of surgical complications (20% vs 15.2%), longer hospital stay (10 ± 6.2 vs 8.4 ± 4.2 days), 30-day readmissions (15% vs 6.3%), and mortality at six (10% vs 3%) and twelve months (20% vs 6.1%), although it was not statistically significant. CONCLUSION: CGA and prehabilitation can classify patients according to their frailty status, support clinicians in decision-making to achieve tailored treatment, and detect clinical conditions for intervention in multiple domains of health in the perioperative period.

Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations.

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.

Improving hip fracture care in Spain: evolution of quality indicators in the Spanish National Hip Fracture Registry.

This study was carried out to analyze the evolution of the quality indicators in the Spanish National Hip Fracture Registry, after disseminating a series of recommendations based on available clinical practice guidelines to the participating hospitals. Six of the seven proposed quality indicators showed a significant improvement. PURPOSE: The Spanish National Hip Fracture Registry (RNFC) arises from the need to know the process and improve the quality of care. Our goal was to analyze the changes in the RNFC's quality indicators after an intervention based on disseminating specific recommendations among the participating hospitals, following available clinical practice guidelines. METHODS: Study comparing before and after performing an intervention in hospitals participating in the RNFC. Data from the hospitals that registered cases in 2017, and that kept registering cases in 2019. Seven quality indicators were chosen, and a standard to be achieved for each indicator was proposed. The intervention consisted in the dissemination of 25 recommendations with practical measures to improve each quality indicator, based on available clinical practice guidelines, by drafting and publishing a scientific paper and sending it via email and printed cards. Fulfilment of each quality indicator was measured after carrying out the intervention. RESULTS: Forty-three hospitals registered 2674 cases between January and May, 2017, and 8037 during 2019. The quality indicators chosen and the degree of compliance were (all with p<0.05): (1) surgery ≤48 h increased from 38.9 to 45.8%; (2) patients mobilised on the first postoperative day increased from 58.9 to 70.3%; (3) patients with anti-osteoporotic medication at discharge increased from 34.5 to 49.8%; (4) patients with calcium supplements at discharge increased from 48.7 to 62.8%; (5) patients with vitamin D supplements at discharge increased from 71.5 to 84.7%; (6) patients developing a grade >2 pressure ulcer during admission decreased from 6.5 to 5.0%; (7) patients able to move on their own at 1 month fell from 58.8 to 56.4%. More than 48% of hospitals improved the proposed indicators. CONCLUSION: Establishing quality indicators and standards and intervening through the dissemination of specific recommendations to improve these indicators achieved an improvement in hospital performance results on a national level.