Organ preservation after neoadjuvant long-course chemoradiotherapy versus short-course radiotherapy.

BACKGROUND: Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined. PATIENTS AND METHODS: This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). RESULTS: Patient and tumor characteristics were similar between LCCRT (n = 247) and SCRT (n = 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P = 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P = 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively. CONCLUSIONS: While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation.

Progressive plasticity during colorectal cancer metastasis.

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

SARS-CoV-2 seroprevalence in workers from a Colombian University Hospital.

BACKGROUND: Antibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection. AIMS: To describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia. METHODS: In this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT-PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT-PCR/antigen test (<3 months, 3-6 months, >6 months). RESULTS: We included 1021 workers (80% women, median age 34 years (interquartile range 28-42), 73% medical personnel, 23% with previous positive RT-PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6-37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT-PCR/antigen test, the seroprevalence was 90% (<3 months), 82% (3-6 months) and 48% (>6 months). In participants with a previous negative RT-PCR/antigen test, the seroprevalence was 17% (<3 months), 21% (3-6 months) and 29% (>6 months). CONCLUSIONS: High IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT-PCR/antigen status and time elapsed since the diagnostic test.

[Efficacy of tele-rehabilitation in patients with chronic obstructive pulmonary disease: a systematic review].

The COVID-19 pandemic has required the use of new technologies to carry out rehabilitation sessions for COP D remotely. The aim of this systematic review was to analyse the available evidence on the efficacy of telerehabilitation in COPD patients. PubMed, WOS, PEDro and Cochrane databases were consulted. The systematic review included nine clinical trials, 55.5% of which display good methodological quality. The most commonly used rehabilitation methods were applications or software for real-time video-calls, visualisation of exercises and recording progress. TR was as effective as outpatient pulmonary rehabilitation, with greater benefits in functional capacity, self-efficacy, mental health, exacerbations and emergency care visits, offering a cost-effective option with high patient satisfaction. The small number of studies and the variety of rehabilitation methods examined limit the value of the evidence obtained.

Estudios mamográficos en un centro metropolitano de referencia en imágenes mamarias: Chile 2008-2018 ¿Vamos por el camino correcto? / Analysis of mammograms performed in a public imaging center in Santiago, Metropolitan Region Chile 2008-2018

BACKGROUND: Mammograms are one of the most effective preventive means for the early detection of breast cancer. OBJECTIVE: To describe the features of patients and results of mammograms performed at a public breast imaging service of the Santiago Metropolitan Area. MATERIAL AND METHODS: We reviewed the reports of mammograms performed on 174,017 women and 18 men, between 2008 and 2018 in an Imaging Center. The BI-RADS classification was used in the reports. RESULTS: Forty-six percent of mammograms (75,781) were reported as BI-RADS 2. The high proportion of BI-RADS 4 reports (674 reports) was seen in patients aged 40 to 49 years, corresponding to 30% of reports in this age range. Among patients aged 50 to 59 years, there were 779 BI-RADS 4 reports (35%). BI-RADS 5 reports were more common among patients aged 50 to 59 years (50 reports, 30%) and among patients aged 70 years or older (83 reports, 28%). CONCLUSIONS: The presence of a significant number of women between 40 and 49 years of age with a BI-RADS 4 mammography result stands out; being an opportunity to develop new clinical research and public health strategies within the framework of the Universal Health Care policy for breast cancer in Chile.

The role of afforestation species as a driver of Hg accumulation in organic horizons of forest soils from a Mediterranean mountain area in SW Europe.

Forest areas are a primary sink of atmospheric mercury (Hg) within terrestrial ecosystems, whereas forest vegetation plays a key role in atmospheric Hg transfer to soil horizons. This study assessed variations in total Hg contents (HgT) and accumulation (HgRes) in the soil organic horizons of a forest area in NE Portugal, where post-wildfire afforestation led to the substitution of the native deciduous species (Quercus pyrenaica) by fast-growing coniferous species (Pseudotsuga menziesii and Pinus nigra). The study also evaluated, for each species, the links between Hg contents and other biophilic elements of soil organic matter (C, N, S) present in organic subhorizons (OL, OF, OH). Mean HgT in the organic horizons of the different tree species follow the sequence: P. nigra (88 µg kg-1) < Q.pyrenaica (101 µg kg-1)

[Analysis of mammograms performed in a public imaging center in Santiago, Metropolitan Region Chile 2008-2018]. / Estudios mamográficos en un centro metropolitano de referencia en imágenes mamarias: Chile 2008-2018 ¿Vamos por el camino correcto?

BACKGROUND: Mammograms are one of the most effective preventive means for the early detection of breast cancer. OBJECTIVE: To describe the features of patients and results of mammograms performed at a public breast imaging service of the Santiago Metropolitan Area. MATERIAL AND METHODS: We reviewed the reports of mammograms performed on 174,017 women and 18 men, between 2008 and 2018 in an Imaging Center. The BI-RADS classification was used in the reports. RESULTS: Forty-six percent of mammograms (75,781) were reported as BI-RADS 2. The high proportion of BI-RADS 4 reports (674 reports) was seen in patients aged 40 to 49 years, corresponding to 30% of reports in this age range. Among patients aged 50 to 59 years, there were 779 BI-RADS 4 reports (35%). BI-RADS 5 reports were more common among patients aged 50 to 59 years (50 reports, 30%) and among patients aged 70 years or older (83 reports, 28%). CONCLUSIONS: The presence of a significant number of women between 40 and 49 years of age with a BI-RADS 4 mammography result stands out; being an opportunity to develop new clinical research and public health strategies within the framework of the Universal Health Care policy for breast cancer in Chile.

Cost-utility analysis of ceftazidime-avibactam versus colistin-meropenem in the treatment of infections due to Carbapenem-resistant Klebsiella pneumoniae in Colombia.

BACKGROUND: Ceftazidime-Avibactam (CAZ-AVI) is a new antimicrobial against carbapenem-resistant Klebsiella pneumoniae. The aim of the study is to examine the cost-effectiveness of CAZ-AVI compared to colistin-meropenem (COL+MEM) in Colombia. METHODS: A decision tree model was developed from health-care system perspective assuming a 30-day time horizon. The clinical course was simulated based on treatment response between 48 and 72 hours, and the duration of the treatment was 7-14 days. Cost inputs were extracted from a published Colombian manual tariffs and official databases, expressed in 2019 dollars (USD). RESULTS: In the base case analysis, CAZ-AVI was associated with reduced mortality, length of hospital stay and fewer add-on antibiotics, resulting in an increase of 1.76 QALYs per patient versus COL+MEM and incremental costs associated in CAZ-AVI were $2,521 higher per patient compared to COL+MEM ($755 versus $3,276). The incremental costs were partially increased due to the lower mortality rate observed with CAZ-AVI. The incremental cost-effectiveness ratio was estimated to be $3,317 per QALY. In the probabilistic sensitivity analysis, with a willingness to pay above $2,438, CAZ-AVI has higher probability of being cost-effective. CONCLUSION: CAZ-AVI demonstrates cost-effectiveness as a treatment for Carbapenem-resistant Klepsiella pneumoniae infections by reducing the number of deaths and increasing QALYs. EXPERT COMMENTARY: Previous studies and surveillance programs from Colombia have reported prevalence of pathogens and the antimicrobial susceptibility of infections caused by multidrug-resistant Gram-negative bacteria. The health authorities have to consider and plan adequate surveillance systems in order to predict the resistance type and in choose the optimal antibiotics when infections occur.

Severity and duration of allergic conjunctivitis: are they associated with severity and duration of allergic rhinitis and asthma?

Summary: Objective. The association of allergic conjunctivitis (AC) with rhinitis and/or asthma is poorly understood. The objective of this study was to apply the Consensus Document for Allergic Conjunctivitis (DECA) criteria for the classification of AC to a population of patients with AC to assess the association between the severity and duration of AC and rhinitis and/or asthma. Methods. Patients with ocular symptoms of AC who participated in the 'Alergológica 2015' study were included. The demographics, classification according to the DECA criteria, etiology, and comorbidities were evaluated by age groups (less or equal than 14 and greater than 14 years). Results. A total of 2,914 patients (age range, 1-90 years) were included in the "Alergológica 2015" study. Of these, 965 patients (33.1%) were diagnosed with AC (77.5% > 14 years). AC was classified as severe, moderate, or mild in 1.8%, 46.4%, and 51.8%, respectively; and as intermittent or persistent in 51.6% and 48.4% of the patients. AC alone occurred in 4% of patients. AC was mainly associated with rhinitis (88.4%), asthma (38.2%), food allergy (8.3%) and atopic dermatitis (3.5%). In allergic respiratory disease rhinitis preceded AC and asthma developed later. The severity and duration of AC was significantly associated with severity and duration of rhinitis (p less than 0.001 for both age groups) and asthma (p less than 0.001 only in adults). Conclusions. The application of the new DECA classification for AC reveals a direct relationship between AC, rhinitis and asthma respect to severity and duration. These relationships suggest that AC should be considered an integral part of the "one airway, one disease" hypothesis.

The Full Spectrum of COVID-19 Development and Recovery Among Kidney Transplant Recipients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) fatality rate is high among kidney transplant recipients. Among survivors, kidney outcomes, seroconversion, and persistence of viral shedding are unexplored. METHODS: Single-center prospective cohort study including data from kidney transplant recipients with confirmed COVID-19 between March 20, 2020 and July 31, 2020. Outcomes were adjudicated until August 31, 2020 or the date of death. RESULTS: There were 491 patients with COVID-19 among the 11 875 recipients in follow-up. The majority were middle aged with ≥1 comorbidities. Thirty-one percent were treated at home, and 69% required hospitalization. Among the hospitalized, 61% needed intensive care, 75% presented allograft dysfunction, and 46% needed dialysis. The overall 28-day fatality rate was 22% and among hospitalized patients it was 41%. Age (odds ratio, 3.08; 95% confidence interval, 1.86-5.09), diabetes mellitus (odds ratio, 1.69; 95% confidence interval, 1.06-2.72), and cardiac disease (odds ratio, 2.00; 95% confidence interval, 1.09-3.68) were independent factors for death. Among the 351 survivors, 19% sustained renal graft dysfunction, and there were 13 (4%) graft losses. Biopsy (n = 20) findings were diverse but decisive to guide treatment and estimate prognosis. Seroconversion was observed in 79% of the survivors and was associated with disease severity. Persistence of viral shedding was observed in 21% of the patients without detectable clinical implications. CONCLUSIONS: This prospective cohort analysis confirms the high 28-day fatality rate of COVID-19, associated primarily with age and comorbidities. The high incidence of allograft dysfunction was associated with a wide range of specific histologic lesions and high rates of sequelae and graft loss. Seroconversion was high and the persistence of viral shedding deserves further studies.

[Usefulness of diaphragmatic ultrasound in predicting extubation success]. / Utilidad de la ecografía diafragmática para predecir el éxito en la extubación.

OBJECTIVE: To evaluate the diagnostic accuracy of diaphragmatic ultrasound in predicting extubation success. DESIGN: A diagnostic accuracy study was carried out. SCOPE: Intensive Care Unit of an Academic hospital in the city of Bogotá (Colombia). PATIENTS OR PARTICIPANTS: A consecutive sample of patients >18 years of age subjected to invasive mechanical ventilation for >48h. INTERVENTIONS: Diaphragmatic ultrasound evaluation at the end of spontaneous ventilation testing. MAIN VARIABLES OF INTEREST: Diaphragmatic excursion (DE, cm), inspiration time (TPIAdia, s), diaphragm contraction speed (DE/TPIAdia, cm/s) and total time (Ttot, s) were evaluated, together with thickening fraction (TFdi, %). RESULTS: A total of 84 patients were included, 79.8% (n=67) with successful extubation and 20.2% (n=17) with failed extubation. The variable with the best discriminatory capacity in predicting extubation success was diaphragm contraction speed, with AUC-ROC 0.70 (p=0.008). CONCLUSIONS: Diaphragm contraction speed exhibited acceptable discriminatory capacity. Ultrasound could be part of a multifactorial approach in the extubation process.

The influence of hospital antimicrobial use on carbapenem-non-susceptible Enterobacterales incidence rates according to their mechanism of resistance: a time-series analysis.

BACKGROUND: Carbapenem non-susceptible Enterobacterales (CNSE) can be broadly divided into those that produce carbapenemases (carbapenemase-producing Enterobacterales (CPE)), and those that harbour other mechanisms of resistance (non-carbapenemase-producing CNSE (NCP-CNSE)). AIM: To determine the predictors of CNSE nosocomial incidence rates according to their mechanism of resistance. METHODS: A time-series analysis was conducted (July 2013 to December 2018) to evaluate the relationship in time between hospital antibiotic use and the percentage of adherence to hand hygiene with the CNSE rates. FINDINGS: In all, 20,641 non-duplicated Enterobacterales isolates were identified; 2.2% were CNSE. Of these, 48.1% and 51.9% were CPE and NCP-CNSE, respectively. Of the CPE, 78.3% possessed a blaOXA-232 gene. A transfer function model was identified for CNSE, CPE, and OXA-232 CPE that explained 20.8%, 19.3%, and 24.2% of their variation, respectively. According to the CNSE and CPE models, an increase in piperacillin-tazobactam (TZP) use of 1 defined daily dose (DDD) per 100 hospital patient-days (HPD) would lead to an increase of 0.69 and 0.49 CNSE and CPE cases per 10,000 HPD, respectively. The OXA-232 CPE model estimates that an increase of 1 DDD per 100 HPD of TZP use would lead to an increase of 0.43 OXA-232 CPE cases per 10,000 HPD. A transfer function model was not identified for NCP-CNSE, nor was there an association between the adherence to handhygiene and the CNSE rates. CONCLUSION: The use of TZP is related in time with the CPE nosocomial rates, mostly explained by its effect on OXA-232 CPE.

Phytotoxicity assays with hydroxyapatite nanoparticles lead the way to recover firing range soils.

Shooting activities is an important source of Pb in contaminated soils. Lead accumulates in superficial soil horizons because of its low mobility, favouring its uptake by plants and representing a high transference risk to the trophic chain. A combination of phytoremediation with nanoremediation techniques can be used to recover firing range soils and decrease the mobility, bioavailability and toxicity of Pb. This study examines in depth the changes in Pb behaviour in firing range soils by adding hydroxyapatite nanoparticles (HANPs). These nanoparticles (NPs) may immobilise Pb and improve the quality of these areas. The use of HANPs and the Pb effects were assessed in three different species (Sinapis alba L., Lactuca sativa L. and Festuca ovina L.), focusing on their germination and early growth, through phytotoxicity assays. Single extractions with CaCl2 (0.01 M) in soils treated with HANPs show that these NPs retained Pb and reduced highly its availability and mobility. HR-TEM and TOF-SIMS were used to determine the interactions between HANPs and Pb, as well as with soil components. According to TOF-SIMS and HR-TEM/EDS analysis, Pb was mainly retained by HANPs but also associated lightly to organic matter, Fe compounds and silicates. Phytotoxicity assays exposed that S. alba, L. sativa and F. ovina were able to germinate and develop in the firing range soils despite the high available Pb contents before adding HANPs. After adding HANPs, Pb retention increased, favouring the germination and the growth of roots in the three species. These results suggest that HANPs can be used to decrease the availability and the toxicity of Pb without negative effects in the species growth. Accordingly, the combination of phytoremediation and nanoremediation techniques can be a great tool to stabilise these soils, avoiding the Pb transfer to nearby areas and its entry in the trophic chain.

Evaluación del uso de antibióticos en mujeres embarazadas con infección urinaria en el Centro de Salud ¨Juan Eulogio Pazymiño¨ del Distrito de Salud 23D02 / Evaluation of the use of antibiotics in pregnant women with infection urinary at the ¨Juan Eulogio Pazymiño¨ Health Center of the Health District 23D02

RESUMEN Introducción: cada año el índice de infección de vías urinarias es mayor por lo que constituye un problema a nivel mundial. Su inadecuado manejo terapéutico ha derivado en la necesidad de investigar métodos para disminuir la resistencia bacteriana. Las mujeres embarazadas son muy vulnerables a contraer este tipo de infección. Material y métodos: se realizó un estudio retrospectivo de utilización de medicamentos del tipo prescripción-indicación en 64 mujeres embarazadas de la provincia de Santo Domingo de los Tsáchilas, en el Distrito de Salud 23D02, en el centro de Salud Juan Eulogio PazyMiño; en base a la información recopilada se desarrolló un programa de atención farmacéutica basado en el método Dáder para mejorar la calidad de la prescripción y contribuir a la disminución de la resistencia bacteriana en mujeres embarazadas con infección de vías urinarias que consumen antibióticos. Resultados: las pacientes con mayor incidencia con infección urinaria tenían entre 10 y 19 años de edad (48,44 %), la bacteria más frecuente fue la Escherichia coli (55,17 %), el medicamento con mayor resistencia bacteriana fue la cefalexina de 500 mg, se identificaron 2 tipos de Problemas Relacionados con Medicamentos (PRM) a predominio del PRM4 (85,29 %), la intervención farmacéutica realizada farmacéutico-médico fue aceptada en un 86,95 %. Conclusiones: la investigación permitió proponer un programa de atención farmacéutica basado en el método Dáder para identificar los problemas relacionados con este grupo farmacológico.

SUMMARY Introduction: the rate of urinary tract infections has increased during the last years, which constitutes a worldwide problem; therefore, the need to investigate methods to reduce bacterial resistance has emerged from inadequate therapeutic management. Pregnant women are more vulnerable to contracting this type of infection. Material and Methods: a retrospective study in the use of medicines of the type prescription - indication was conducted with 64 pregnant women at Juan Eulogio PazyMiño Health Center, which belongs to the 23D02 Health District located in Santo Domingo de los Tsachilas province. Based on the information gathered, a pharmaceutical care program established on the Dader method was developed to improve the prescription quality and thus contribute to the reduction of bacterial resistance in pregnant women with urinary tract infections who consume antibiotics. Results: patients with a higher incidence of urinary tract infections were between 10 and 19 years of age (48.44%), the most common bacteria found was Escherichia coli (55.17%), and, the drug with the highest bacterial resistance was cephalexin of 500 mg. Two types of Medication-Related Problems (MRP) were identified where the most frequent was MRP4 (85.29%). Pharmaceutical - medical intervention was accepted in 86.95% of the doctors. Conclusions: the research allowed to propose a Pharmaceutical Assistance Program based on the Dader method to identify the problems related to this pharmacological group.

EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer.

BACKGROUND: Although EGFR mutant tumors exhibit low response rates to immune checkpoint blockade overall, some EGFR mutant tumors do respond to these therapies; however, there is a lack of understanding of the characteristics of EGFR mutant lung tumors responsive to immune checkpoint blockade. PATIENTS AND METHODS: We retrospectively analyzed de-identified clinical and molecular data on 171 cases of EGFR mutant lung tumors treated with immune checkpoint inhibitors from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, University of California Los Angeles, and Dana Farber Cancer Institute. A separate cohort of 383 EGFR mutant lung cancer cases with sequencing data available from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, and The Cancer Genome Atlas was compiled to assess the relationship between tumor mutation burden and specific EGFR alterations. RESULTS: Compared with 212 EGFR wild-type lung cancers, outcomes with programmed cell death 1 or programmed death-ligand 1 (PD-(L)1) blockade were worse in patients with lung tumors harboring alterations in exon 19 of EGFR (EGFRΔ19) but similar for EGFRL858R lung tumors. EGFRT790M status and PD-L1 expression did not impact response or survival outcomes to immune checkpoint blockade. PD-L1 expression was similar across EGFR alleles. Lung tumors with EGFRΔ19 alterations harbored a lower tumor mutation burden compared with EGFRL858R lung tumors despite similar smoking history. CONCLUSIONS: EGFR mutant tumors have generally low response to immune checkpoint inhibitors, but outcomes vary by allele. Understanding the heterogeneity of EGFR mutant tumors may be informative for establishing the benefits and uses of PD-(L)1 therapies for patients with this disease.