Tuberculosis contact tracing, Angola.

Objective: To assess the outcomes of a contact-tracing programme to increase the diagnosis of tuberculosis in Cubal, Angola and offer preventive treatment to high-risk groups. Methods: A health centre-based contact-tracing programme was launched in Hospital Nossa Senhora da Paz in March 2015 and we followed the programme until 2022. In that time, staffing and testing varied which we categorized as four periods: medical staff reinforcement, 2015-2017, with a doctor seconded from Vall d'Hebron University Hospital, Spain; routine staff, 2017-2021, with no external medical support; community directly observed treatment (DOT), 2018-2019 with community worker support; and enhanced contact tracing, 2021-2022, with funding that allowed free chest radiographs, molecular and gastric aspirate testing. We assessed differences in contacts seen each month, and testing and treatment offered across the four periods. Findings: Overall, the programme evaluated 1978 contacts from 969 index cases. Participation in the programme was low, although it increased significantly during the community DOT period. Only 16.6% (329/1978) of contacts had a chest radiograph. Microbiological confirmation increased to 72.2% (26/36) after including molecular testing, and 10.1% (200/1978) of contacts received treatment for tuberculosis. Of 457 contacts younger than 5 years, 36 (7.9%) received preventive tuberculosis treatment. Half of the contacts were lost to follow-up before a final decision was taken on treatment. Conclusion: Contact tracing increased the diagnosis of tuberculosis although engagement with the programme was low and loss to follow-up was high. Participation increased during community DOT. Community-based screening should be explored to improve participation and diagnosis.

Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients.

PURPOSE: Prognostic and predictive biomarkers to cyclin-dependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA (ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy. EXPERIMENTAL DESIGN: Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model. RESULTS: 201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms. CONCLUSIONS: We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor-positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted.

CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2- Metastatic Breast Cancer.

PURPOSE: In hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC), it is imperative to identify patients who respond poorly to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and to discover therapeutic targets to reverse this resistance. Non-luminal breast cancer subtype and high levels of CCNE1 are candidate biomarkers in this setting, but further validation is needed. EXPERIMENTAL DESIGN: We performed mRNA gene expression profiling and correlation with progression-free survival (PFS) on 455 tumor samples included in the phase III PEARL study, which assigned patients with HR+/HER2- MBC to receive palbociclib+endocrine therapy (ET) versus capecitabine. Estrogen receptor-positive (ER+)/HER2- breast cancer cell lines were used to generate and characterize resistance to palbociclib+ET. RESULTS: Non-luminal subtype was more prevalent in metastatic (14%) than in primary tumor samples (4%). Patients with non-luminal tumors had median PFS of 2.4 months with palbociclib+ET and 9.3 months with capecitabine; HR 4.16, adjusted P value < 0.0001. Tumors with high CCNE1 expression (above median) also had worse median PFS with palbociclib+ET (6.2 months) than with capecitabine (9.3 months); HR 1.55, adjusted P value = 0.0036. In patients refractory to palbociclib+ET (PFS in the lower quartile), we found higher levels of Polo-like kinase 1 (PLK1). In an independent data set (PALOMA3), tumors with high PLK1 show worse median PFS than those with low PLK1 expression under palbociclib+ET treatment. In ER+/HER2- cell line models, we show that PLK1 inhibition reverses resistance to palbociclib+ET. CONCLUSIONS: We confirm the association of non-luminal subtype and CCNE1 with resistance to CDK4/6i+ET in HR+ MBC. High levels of PLK1 mRNA identify patients with poor response to palbociclib, suggesting PLK1 could also play a role in the setting of resistance to CDK4/6i.

Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2- advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial.

BACKGROUND: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone. METHODS: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1. RESULTS: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade ≥3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade ≥3 neutropenia and anemia. Efficacy results were consistent with the global study. CONCLUSIONS: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2- ABC, including populations of interest (NCT02941926). TRIAL REGISTRATION: ClinicalTrials.gov NCT02941926.

Accuracy and Limitations of Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients with Positive Nodes.

Background: Axillary surgical management in patients with node-positive breast cancer at the time of diagnosis converted to negative nodes through neoadjuvant chemotherapy (NAC) remains unclear. Removal of more than two sentinel nodes (SLNs) in these patients may decrease the false negative rate (FNR) of sentinel lymph node biopsies (SLNBs). We aim to analyse the detection rate (DR) and the FNR of SLNB assessment according to the number of SLNs removed. Methods: A retrospective study was performed from October 2012 to December 2018. Patients with invasive breast cancer who had a clinically node-positive disease at diagnosis and with a complete axillary response after neoadjuvant chemotherapy were selected. Patients included underwent SLNB and axillary lymph node dissection (ALND) after NAC. The SLN was considered positive if any residual disease was detected. Descriptive statistics were used to describe the clinicopathologic features and the results of SLNB and ALND. The DR of SLNB was defined as the number of patients with successful identification of SLN. Presence of residual disease in ALND and negative SLN was considered false negative. Results: A total of 368 patients with invasive breast cancer who underwent surgery after complete NAC were studied. Of them, 85 patients met the eligibility criteria and were enrolled in the study. The mean age at diagnosis was 50.8 years. Systematic lymphadenectomy was performed in all patients, with an average of 10 lymph nodes removed. The DR of SLNB was 92.9%, and the FNR was 19.1. The median number of SLNs removed was 3, and at least, three SLNs were obtained in 42 patients (53.2%). When at least three sentinel nodes were removed, the FNR decreased to 8.7%. Conclusions: In this cohort, the SLN assessment was associated with an adequate DR and a high FNR. Removing three or more SLNs decreased the FNR from 19.1% to 8.7%. Complementary approaches may be considered for axillary lymph node staging after neoadjuvant chemotherapy. The study was approved by our institution's ethics committee (Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain) (https://clinicaltrials.gov/ct2/show/NCEI:20/0048).

Feasibility of targeted axillary dissection for de-escalation of surgical treatment after neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Targeted axillary dissection, which combines sentinel lymph node biopsy with removal of the proven involved node noted during the staging process, has been shown to improve axillary staging and decrease false negative rates after neoadjuvant chemotherapy in patients with breast cancer. OBJECTIVE(S): The main goal of this study was to assess the ability to identify and remove the clipped node and the false negative rate of targeted axillary dissection. METHODS: We performed a prospective study among patients with biopsy-confirmed nodal metastases who received neoadjuvant chemotherapy. A clip was placed on the sample node prior systemic therapy. After neoadjuvant chemotherapy, all patients underwent sentinel lymph node biopsy (dual tracer), localization and excision of the clipped node and axillary lymph node dissection. The clipped node was preoperatively localized in all cases placing an iodine-125 seed guided by ultrasound. The pathology of the sentinel nodes and clipped node was compared with other nodes. RESULTS: A total of 455 patients with invasive breast cancer were studied. Of the 148 patients with NAC, 32 met the eligibility criteria and were enrolled in the study. Mean age at diagnosis was 52.3 years. Systematic lymphadenectomy was performed in all patients, with an average of 14.3 lymph nodes removed. Detection rate of the clipped node alone was 96.9%, and 100% for targeted axillary dissection. Ability of clipped node alone to predict nodal status showed a FNR of 10,5% while SLNB alone performed by dual tracer and targeted axillary dissection, showed FNRs of 5.3% and 5.0%, respectively. Sentinel lymph nodes matched clipped node in 23 patients (74.2%). CONCLUSION (S): In node positive breast cancer patients, targeted axillary dissection is a reliably approach for axillary staging after neoadjuvant chemotherapy. The preoperative location of the clipped node is mandatory to increase the detection rate and optimize the results of the technique.

Characterization of plasma circulating small extracellular vesicles in patients with metastatic solid tumors and newly diagnosed brain metastasis.

Nearly 40% of the advanced cancer patients will present brain metastases during the course of their disease, with a 2-year life expectancy of less than 10%. Immune system impairment, including the modulation of both STAT3 and PD-L1, is one of the hallmarks of brain metastases. Liquid biopsy could offer several advantages in brain metastases management, such as the possibility of noninvasive dynamic monitoring. Extracellular vesicles (EVs) have been recently proposed as novel biomarkers especially useful in liquid biopsy due to their secretion in biofluids and their role in cell communication during tumor progression. The main aim of this work was to characterize the size and protein cargo of plasma circulating EVs in patients with solid tumors and their correlation with newly diagnosed brain metastases, in addition to their association with other relevant clinical variables. We analyzed circulating EVs in the plasma of 123 patients: 42 patients with brain metastases, 50 without brain metastases and 31 healthy controls. Patients with newly diagnosed brain metastases had a lower number of circulating EVs in the plasma and a higher protein concentration in small EVs (sEVs) compared to patients without brain metastases and healthy controls. Interestingly, melanoma patients with brain metastases presented decreased STAT3 activation and increased PD-L1 levels in circulating sEVs compared to patients without central nervous system metastases. Decreased STAT3 activation and increased PD-L1 in plasma circulating sEVs identify melanoma patients with brain metastasis.

Biology of the Triple-Negative Breast Cancer: Immunohistochemical, RNA, and DNA Features.

BACKGROUND: The triple-negative breast cancer (TNBC) constitutes a heterogeneous disease with an aggressive behavior and a poor prognosis. A better understanding of its biology is required to identify new biomarkers and improve clinical outcomes. SUMMARY: To date, the definition and classification of TNBC depends on a multiomic approach including immunohistochemistry (IHC), genomic, and transcriptomic features, and the tumor immune landscape. The development of new technologies has allowed us to sequence the whole cancer genome. The Cancer Genome Atlas (TCGA) and next-generation sequencing have led to a greater knowledge of DNA alterations such as TP53 or BRCA mutations, copy number variations, and DNA methylations. In addition, gene expression profiling has allowed to define a molecular intrinsic classification of TNBC based on mRNA. IHC and genomic profiling are also necessary to identify new immune biomarkers such as the presence of tumor-infiltrating lymphocytes and the expression of immune checkpoint molecules. KEY MESSAGES: This review aimed to provide recent knowledge of TNBC biology and classification focused on IHC, transcriptomics, genomic features, and the new immune biomarkers.

The fight against multidrug-resistant organisms: The role of ZnO crystalline defects.

This article reports the excellent antimicrobial response of nanoparticulate ZnO against multidrug-resistant organisms (MDROs). We demonstrate that the enhanced antimicrobial activity against MDROs depends on the crystalline defects of ZnO. Hence, this work provides insights on the ZnO-microorganism interactions, and we pose combined physico-chemical action mechanisms against resistant bacteria.

Safety of eribulin as third-line chemotherapy in HER2-negative, advanced breast cancer pre-treated with taxanes and anthracycline: OnSITE study.

Eribulin is active and safe in heavily pre-treated metastatic breast cancer patients. Few safety data have been published in third line. We aimed to report the specific safety profile on third line beyond taxanes and anthracyclines in advanced breast cancer (ABC). A multicenter phase II, prospective study was conducted in anthracyclines and taxanes pre-treated HER2-negative ABC, programmed to receive eribulin as third-line chemotherapy. Adverse events (AEs) were assessed and classified according to CTCAE. In addition, efficacy, in terms of overall survival (OS) and progression-free survival (PFS), and the dynamics of circulating tumor cells (CTCs) during treatment were assessed. 59 patients fulfilled the criteria. All but one showed AEs with a cumulative number of 598 AEs. The most frequent grade 3/4 drug-related AEs were neutropenia (1.7%), febrile neutropenia (0.5%), leukopenia (0.5%), alopecia (0.5%), asthenia (0.3%), elevated gamma glutamyl transferase levels (0.2%), and respiratory tract infection (0.2%). Median PFS was 4 months (95% CI 3.1-5.9) and median OS was 13.6 months (11.8-not reached). The mean number of CTCs in peripheral blood was significantly reduced from baseline to cycle 2 (16.8 vs 5.4 CTCs; P < 0.001). Median OS was significantly longer in <5 baseline CTC patients compared to ≥5 baseline CTC patients (13.1 months [95% CI: 11.8-not reached] vs 12.5 months [95% CI: 7.6-not reached]; P = 0.045). A significant correlation (P = 0.0129) was observed between CTC levels at cycle 2 and death when CTCs were analyzed using cox regression. Eribulin chemotherapy is effective and safe as third line in advanced HER2-negative breast cancer. CTC levels correlate with overall survival.

Ultrasound Evolution of Pediatric Urinary Schistosomiasis after Treatment with Praziquantel in a Highly Endemic Area.

Urinary schistosomiasis causes damage to the urological system. Ultrasound is a method that detects the burden of secondary disease, individually and in epidemiological studies. In this study, the Schistosoma haematobium-associated urinary tract pathology is analyzed before and after treatment in a short period of time. Seventy children who had previously participated in an epidemiological study on schistosomiasis in the city of Cubal, Angola, and had also performed urinary ultrasound between August 2013 and February 2014 were cited 6-8 months later to assess the possible reinfection and repeat new urinary ultrasound, analyzing changes at the level of urinary pathology. The presence of hematuria and proteinuria was also analyzed. Of the 70 children analyzed, 29 (41.4%) were girls, with an average age of 10.4 years (standard deviation 2.3). Fifty-three (75.7%) had an improvement in their bladder and/or kidney scores, whereas 12 (17.1%) had no change and five (7.1%) had progression of the disease. None of the parameters analyzed completely disappeared. After one single course of treatment with praziquantel, all the analyzed parameters showed regression. Improvement was greater in the urinary bladder than in the upper urinary tract, though these lesions also reversed; the reversion of all parameters was greater among children older than 10 years old than the younger ones. Proteinuria was the parameter with a smaller reduction. Ultrasound should be a usual tool for diagnosis and follow-up in urinary schistosomiasis, particularly in children; more accurate recommendations about follow-up in the case of children whose lesions do not reverse should be established.

Drug Resistance of Mycobacterium tuberculosis Complex in a Rural Setting, Angola.

We found high prevalence rates of multidrug-resistant tuberculosis among retreatment patients (71.1%) and persons with new cases (8.0%) in Angola. These findings are of concern but should be interpreted with caution. A national drug-resistance survey is urgently needed to determine the actual prevalence of multidrug-resistant tuberculosis in Angola.

Ultrasound findings and associated factors to morbidity in Schistosoma haematobium infection in a highly endemic setting.

OBJECTIVE: To evaluate the usefulness of the WHO classification of ultrasound pathological changes and to establish risk factors for morbidity in a highly endemic setting. METHODS: One hundred and fifty-seven ultrasounds were performed on school-aged children previously diagnosed with urinary schistosomiasis in Cubal, Angola. The findings were analysed according to the WHO guidelines. Factors for morbidity were studied. RESULTS: Mean age of the children was 8.7 (SD 3.2) years. Pathological changes were found in 85.3% (84.7% in the bladder, 34.4% the ureter and 6.3% kidney lesions). The global score according to the WHO classification was 5.74. Male gender [OR 2.61 (1.04-6.58); P 0.043] and older age [OR 2.96 (1.17-7.46); P 0.023] were associated with a higher risk of developing any kind of urinary abnormality. Proteinuria was present in 61.7% of the children. Macroscopic haematuria [OR 2.48 (1.11-5.58); P = 0.02)] and a high level of proteinuria > 300 mg/dl [OR 5.70 (2.17-14.94); P 300 mg/dl)] were associated with abnormalities of the upper urinary tract and showed good positive and negative predictive values for the detection of pathology in the upper urinary tract (65.5% and 71.1%, respectively). CONCLUSIONS: Severe urinary tract pathology was found in a high percentage of the children in our setting. Microhaematuria and proteinuria were good markers of morbidity, proteinuria being more precise for severe alterations of the upper urinary tract. We suggest initial and evolutive ultrasound in children diagnosed with schistosomiasis, and close monitoring including periodic controls. As schistosomiasis control efforts are currently focused on reducing morbidity, tests that detect the presence or degree of morbidity are essential for targeting treatment and tracking the progress of control campaigns.

Prevalence of Strongyloides stercoralis and Other Intestinal Parasite Infections in School Children in a Rural Area of Angola: A Cross-Sectional Study.

Strongyloides stercoralis is widely distributed in the tropics and subtropics. The aim of this study was to determine the prevalence of S. stercoralis and other intestinal parasites and identify the risk factors for infection with S. stercoralis in a rural area of Angola. A cross-sectional study was conducted in school-age children (SAC) in Cubal, Angola. A questionnaire collecting clinical and epidemiological variables was used, and two stool samples were collected. A concentration technique (Ritchie) and a technique for detection of larvae migration (Baermann) were performed. Of 230 SAC, 56.1% were female and the mean age was 9.3 years (SD 2.45). Severe malnutrition, according to body mass index (BMI)-for-age, was observed in 20.4% of the SAC, and anemia was found in 59.6%. Strongyloides stercoralis was observed in 28 of the 230 (12.8%) SAC. Eggs of other helminths were observed in 51 (22.2%) students: Hymenolepis spp. in 27 students (11.7%), hookworm in 14 (6.1%), Schistosoma haematobium in four (1.7%), Enterobius vermicularis in four (1.7%), Ascaris lumbricoides in three (1.3%), Taenia spp. in two (0.9%), and Fasciola hepatica in one (0.4%). Protozoa were observed in 17 (7.4%) students. Detection of S. stercoralis was higher using the Baermann technique versus using formol-ether (11.3 vs. 3%). Overall prevalence of S. stercoralis in the school population of 16 studied schools in the municipal area of Cubal was greater than 10%. This fact must be considered when designing deworming mass campaigns. The use of specific tests in larvae detection is needed to avoid overlooking this parasite.

Exploring New Mechanisms for Effective Antimicrobial Materials: Electric Contact-Killing Based on Multiple Schottky Barriers.

The increasing threat of multidrug-resistance organisms is a cause for worldwide concern. Progressively microorganisms become resistant to commonly used antibiotics, which are a healthcare challenge. Thus, the discovery of new antimicrobial agents or new mechanisms different from those used is necessary. Here, we report an effective and selective antimicrobial activity of microstructured ZnO (Ms-ZnO) agent through the design of a novel star-shaped morphology, resulting in modulation of surface charge orientation. Specifically, we find that Ms-ZnO particles are composed of platelet stacked structure, which generates multiple Schottky barriers due to the misalignment of crystallographic orientations. We also demonstrated that this effect allows negative charge accumulation in localized regions of the structure to act as "charged domain walls", thereby improving the antimicrobial effectiveness by electric discharging effect. We use a combination of field emission scanning electron microscopy (FE-SEM), SEM-cathodoluminescence imaging, and Kelvin probe force microscopy (KPFM) to determine that the antimicrobial activity is a result of microbial membrane physical damage caused by direct contact with the Ms-ZnO agent. It is important to point out that Ms-ZnO does not use the photocatalysis or the Zn2+ released as the main antimicrobial mechanism, so consequently this material would show low toxicity and robust stability. This approach opens new possibilities to understand both the physical interactions role as main antimicrobial mechanisms and insight into the coupled role of hierarchical morphologies and surface functionality on the antimicrobial activity.

Impacto de una intervención multidimensional en pacientes >= 65 años tras un ingreso por neumonía: estudio aleatorizado / Impact of a multidimensional intervention in elderly patients with community-acquired pneumonia: IMIEPCAP clinical trial

Introducción El objetivo principal del estudio es evaluar si una intervención multidimensional en los ancianos que han sido ingresados por neumonía disminuye los reingresos hospitalarios y el número de consultas a urgencias durante el año siguiente a la intervención. Metodología. Ensayo clínico no farmacológico unicéntrico con 2 grupos de estudio paralelos en los que los pacientes son asignados aleatoriamente. Se incluirán 314 pacientes (157 en cada grupo). Serán sujetos del estudio los pacientes ≥ 65 años con índice de Barthel ≥ 60 que ingresen por neumonía. El grupo intervención recibirá a los 2 meses del ingreso por neumonía una intervención geriátrica realizada por un médico y una enfermera en la que se incluyen los siguientes componentes: vacunación, nutrición, estado funcional, estado cognitivo y comorbilidades. El grupo control realizará el seguimiento convencional. Se evaluará al año de la intervención el número de ingresos, consultas a urgencias, estado funcional, supervivencia e institucionalización. Si esta intervención demostrara mejorar las variables estudiadas, dispondríamos de una intervención estandarizada y relativamente sencilla que nos permitiría mejorar los resultados de salud a nivel individual e indirectamente disminuir los costes relacionados con la asistencia a estos pacientes (AU)

Introduction. The main objective of this study is to determine whether a multidimensional intervention applied to elderly patients admitted to hospital due to pneumonia reduces re-admissions and emergency department visits in the year after the intervention. Methodology. This is a single-centre non-pharmacological randomised clinical trial with a parallel design. Three hundred and fourteen patients will be included (157 in each arm). Eligible patients will be ≥ 65 years old and with a Barthel index ≥ 60 that are admitted to hospital due to pneumonia. Participants will be randomised to multidimensional intervention or to control group. Two months after hospital discharge the intervention group will receive a geriatric intervention, carried out by a nurse and a physician. It will include assessment of co-morbidities, nutritional, functional and cognitive status, and immunisation. The control group will receive conventional follow-up. The number of re-admissions, visits to the emergency department, functional status, survival, and institutionalisation will be evaluated one year after intervention. If the intervention shows an improvement in the studied outcomes, it would allow us to improve individual outcomes, and indirectly reduce healthcare costs using a relatively simple, standardised tool (AU)

[Impact of a multidimensional intervention in elderly patients with community-acquired pneumonia: IMIEPCAP clinical trial]. / Impacto de una intervención multidimensional en pacientes ≥65años tras un ingreso por neumonía: estudio aleatorizado.

INTRODUCTION: The main objective of this study is to determine whether a multidimensional intervention applied to elderly patients admitted to hospital due to pneumonia reduces re-admissions and emergency department visits in the year after the intervention. METHODOLOGY: This is a single-centre non-pharmacological randomised clinical trial with a parallel design. Three hundred and fourteen patients will be included (157 in each arm). Eligible patients will be ≥65 years old and with a Barthel index ≥60 that are admitted to hospital due to pneumonia. Participants will be randomised to multidimensional intervention or to control group. Two months after hospital discharge the intervention group will receive a geriatric intervention, carried out by a nurse and a physician. It will include assessment of co-morbidities, nutritional, functional and cognitive status, and immunisation. The control group will receive conventional follow-up. The number of re-admissions, visits to the emergency department, functional status, survival, and institutionalisation will be evaluated one year after intervention. If the intervention shows an improvement in the studied outcomes, it would allow us to improve individual outcomes, and indirectly reduce healthcare costs using a relatively simple, standardised tool.

Targeting the PI3K/AKT/mTOR pathway in estrogen receptor-positive breast cancer.

Approximately 70-75% of breast cancers express the estrogen receptor (ER), indicating a level of dependence on estrogen for growth. Endocrine therapy is an important class of target-directed therapy that blocks the growth-promoting effects of estrogen via ER. Although endocrine therapy continues to be the cornerstone of effective treatment of ER-positive (ER+) breast cancer, many patients with advanced ER+ breast cancer encounter de novo or acquired resistance and require more aggressive treatment such as chemotherapy. Novel approaches are needed to augment the benefit of existing endocrine therapies by prolonging time to disease progression, preventing or overcoming resistance, and delaying the use of chemotherapy. The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is a key intracellular signaling system that drives cellular growth and survival; hyperactivation of this pathway is implicated in the tumorigenesis of ER+ breast cancer and in resistance to endocrine therapy. Moreover, preclinical and clinical evidence show that PI3K/AKT/mTOR pathway inhibition can augment the benefit of endocrine therapy in ER+ breast cancer, from the first-line setting and beyond. This article will review the fundamental role of the PI3K/AKT/mTOR pathway in driving ER+ breast tumors, and its inherent interdependence with ER signaling. In addition, ongoing strategies to combine PI3K/AKT/mTOR pathway inhibitors with endocrine therapy for improved clinical outcomes, and methods to identify patient populations that would benefit most from inhibition of the PI3K/AKT/mTOR pathway, will be evaluated.