Bacteria in metastatic sites: Unveiling hidden players in cancer progression.

Bacteria exhibit key features of cancer metastasis, such as motility, invasion, and modulation of the tumor microenvironment. They migrate through lymphatic and blood systems, invade metastatic tissues, and alter local microenvironments to support metastatic growth. Bacteria also shape the tumor microenvironment, affecting immune responses and inflammation, which influence tumor progression and therapy response. While they hold therapeutic potential, challenges like contamination and complex characterization persist, necessitating advanced sequencing and research for clinical application.

Microbiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development.

Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises concerns regarding potential spurious associations. Here we study the fecal microbiota of 589 patients at different colorectal cancer (CRC) stages and compare observations with up to 15 published studies (4,439 patients and controls total). Using quantitative microbiome profiling based on 16S ribosomal RNA amplicon sequencing, combined with rigorous confounder control, we identified transit time, fecal calprotectin (intestinal inflammation) and body mass index as primary microbial covariates, superseding variance explained by CRC diagnostic groups. Well-established microbiome CRC targets, such as Fusobacterium nucleatum, did not significantly associate with CRC diagnostic groups (healthy, adenoma and carcinoma) when controlling for these covariates. In contrast, the associations of Anaerococcus vaginalis, Dialister pneumosintes, Parvimonas micra, Peptostreptococcus anaerobius, Porphyromonas asaccharolytica and Prevotella intermedia remained robust, highlighting their future target potential. Finally, control individuals (age 22-80 years, mean 57.7 years, standard deviation 11.3) meeting criteria for colonoscopy (for example, through a positive fecal immunochemical test) but without colonic lesions are enriched for the dysbiotic Bacteroides2 enterotype, emphasizing uncertainties in defining healthy controls in cancer microbiome research. Together, these results indicate the importance of quantitative microbiome profiling and covariate control for biomarker identification in CRC microbiome studies.

Effectiveness and Safety of Postoperative Hospital at Home for Surgical Patients: A Cohort Study.

OBJECTIVE: To determine the feasibility and effectiveness of a Hospital at Home (HaH) enabled early transfer pathways for surgical patients. BACKGROUND: HaH serves as a safe alternative to traditional hospitalization by providing acute care to patients in their homes through a comprehensive range of hospital-level interventions. To our knowledge, no studies have been published to date reporting a large cohort of early home-transferred patients after surgery through a HaH unit. METHODS: Cohort study enrolling every patient admitted to the HaH unit of a tertiary hospital who underwent any of 6 surgeries with a predefined early transfer pathway and fitting both general and surgery inclusion criteria (clinical and hemodynamic stability, uncomplicated surgery, presence of a caregiver, among others) from November 2021 to May 2023. Protocols were developed for each pathway between surgical services and HaH to deliver the usual postoperative care in the home setting. Discharge was decided according to protocol. An urgent escalation pathway was also established. RESULTS: During the study period, 325 patients were included: 141 were bariatric surgeries, 85 kidney transplants, 45 thoracic surgeries, 37 cystectomies, 10 appendicectomies, and 7 ventral hernia repairs. The overall escalation of care during HaH occurred in 7.3% of patients and 30-day readmissions in 7%. Most adverse events were managed at home and the overall mortality was zero. The total mean length of stay was 8 days (interquartile range 2-14), and patients with HaH were transferred home 3 days (interquartile range 1-6) earlier than the usual pathway; a total of 1551 bed-days were saved. CONCLUSIONS: The implementation of early home transfer pathways for surgical patients through HaH is feasible and effective, with favorable safety outcomes.

Bacterial co-infection at hospital admission in patients with COVID-19.

OBJECTIVES: We described the current incidence and risk factors of bacterial co-infection in hospitalized patients with COVID-19. METHODS: Observational cohort study was performed at the Hospital Clinic of Barcelona (February 2020-February 2021). All patients with COVID-19 who were admitted for >48 hours with microbiological sample collection and procalcitonin (PCT) determination within the first 48 hours were included. RESULTS: A total of 1125 consecutive adults met inclusion criteria. Co-infections were microbiologically documented in 102 (9.1%) patients. Most frequent microorganisms were Streptococcus pneumoniae (79%), Staphylococcus aureus (6.8%), and Haemophilus influenzae (6.8%). Test positivity was 1% (8/803) for blood cultures, 10.1% (79/780) for pneumococcal urinary antigen test, and 11.4% (15/132) for sputum culture. Patients with PCT higher than 0.2, 0.5, 1, and 2 ng/mL had significantly more co-infections than those with lower levels (p=0.017, p=0.031, p<0.001, and p<0.001, respectively). In multivariate analysis, oxygen saturation ≤94% (OR 2.47, CI 1.57-3.86), ferritin levels <338 ng/mL (OR 2.63, CI 1.69-4.07), and PCT higher than 0.2 ng/mL (OR 1.74, CI 1.11-2.72) were independent risk factors for co-infection at hospital admission owing to COVID-19. CONCLUSIONS: Bacterial co-infection in patients hospitalized for COVID-19 is relatively common. However, clinicians could spare antibiotics in patients with PCT values <0.2, especially with high ferritin values and oxygen saturation >94%.

Impact of Inflammatory Response Modifiers on the Incidence of Hospital-Acquired Infections in Patients with COVID-19.

INTRODUCTION: The study aim was to assess the influence of inflammatory response modifiers, including anti-interleukin-6 (IL-6) biologics and corticosteroids, on the incidence of hospital-acquired infections in patients with coronavirus disease 2019 (COVID-19). METHODS: Case-control study performed at a university hospital from February 26 to May 26, 2020. Cases were defined as patients with COVID-19 who developed hospital-acquired infections. For each case, two controls were selected among patients without infections. Cases and controls were matched obeying three criteria in a hierarchical sequence: length of hospital stay up until the first infection; comorbidity; and need for Intensive care unit (ICU) admission. Conditional logistic regression analysis was used to estimate the association of exposures with being a case. RESULTS: A total of 71 cases and 142 controls were included. Independent predictors for acquiring a hospital infection were chronic liver disease [odds ratio (OR) 16.56, 95% CI 1.87-146.5, p = 0.012], morbid obesity (OR 6.11, 95% CI 1.06-35.4, p = 0.043), current or past smoking (OR 4.15, 95% CI 1.45-11.88, p = 0.008), exposure to hydroxychloroquine (OR 0.2, 95% CI 0.041-1, p = 0.053), and invasive mechanical ventilation (OR 61.5, 95% CI 11.08-341, p ≤ 0.0001). CONCLUSIONS: Inflammatory response modifiers had no influence on acquisition of nosocomial infections in admitted patients with COVID-19. Hospital-acquired infections primarily occurred in the critically ill and invasive mechanical ventilation was the main exposure conferring risk.

Profile of older patients attended in the emergency department after falls: a FALL-ER registry study of the magnitude of the problem and opportunities for improving hospital emergency care. / Perfil de los pacientes ancianos atendidos en urgencias por caídas (Registro FALL-ER): magnitud del problema y posibilidades de mejora en los servicios de urgencias hospitalarios.

OBJECTIVES: To profile patients aged 65 years or older who are attended in a hospital emergency department after falls. To describe the falls, their severity, and factors relevant to recommended preventive measures. MATERIAL AND METHODS: The FALL-ER is a multipurpose, multicenter prospective registry of a systematically described cohort of patients aged 65 years or older attended in 5 hospital emergency departments on 52 days of the same year. We collected data on 68 independent variables. Patients were classified according to whether they had received recommendations related to preventing falls in any of the following categories: exercise, education on fall prevention, referral to a specialist or changes in medication. RESULTS: . A total of 1507 patients or carers were interviewed (93.6% of the 1610 patients in the registry). The cohort was of advanced age and had high rates of comorbidity, polypharmacy, and history of geriatric syndromes. The majority of falls occurred during the day and in the patients home. Half the falls were not witnessed. Forty-eight percent of the patients reported fear of falling, 22% had acute functional impairment, 16% were admitted, and 0.6% died in the hospital. Recommendations directed to preventing falls were received by 509 (33.8%) cases. Loss of hearing acuity, self-reported cognitive impairment, emergency first aid at the site of the fall, fear of falling again, acute functional impairment, and hospitalization were associated with a greater likelihood of receiving recommendations for preventing falls. Loss of visual acuity was associated with a lower likelihood of receiving recommendations. CONCLUSION: Only a third of elderly patients attended in an emergency department after falls receive recommendations that target preventing further falls. Certain patient and fall characteristics are associated with a greater likelihood of receiving such recommendations.

OBJETIVO: Estudiar el perfil de los pacientes de 65 años o más atendidos por una caída en los servicios de urgencias (SU), las características de las caídas, y el grado y los factores asociados con la realización de recomendaciones para prevenir las caídas (RPC). METODO: FALL-ER es un registro de cohortes multipropósito, prospectivo y multicéntrico, con muestreo sistemático, que incluyó todos los pacientes de 65 años o más atendidos por caída en 5 SU durante 52 días en un año. Se recogieron 68 variables independientes. Los pacientes se clasificaron en función de recibir o no RPC (cualquiera de las siguientes: ejercicio, educación sobre prevención de las caídas, derivación a especialista o modificación de fármacos relacionados con las caídas). RESULTADOS: Se analizaron 1.507 (93,6%) del total de 1.610 pacientes. Los pacientes tenían una edad muy avanzada y alto grado de comorbilidad, polifarmacia y síndromes geriátricos previos. La caída suele suceder de día, en domicilio y en la mitad de casos sin testigo. Un 48% refirió miedo a caerse, un 22% presentó deterioro funcional agudo, un 16% ingresó y un 0,6% falleció. Se realizaron RPC en 509 (33,8%) casos. La disminución de la agudeza auditiva, deterioro cognitivo autorreferido, atención médica en el lugar de la caída, miedo a volver a caerse, deterioro funcional agudo y hospitalización se asociaron con mayor probabilidad de RPC, y la disminución de la agudeza visual con menor probabilidad. CONCLUSIONES: Solo tres de cada diez pacientes ancianos atendidos por una caída en urgencias recibe RPC posteriores, aunque existen ciertas características relacionadas con el paciente y la caída que se asocian a una mayor probabilidad de recibirlas.

The yin-yang of kinase activation and unfolding explains the peculiarity of Val600 in the activation segment of BRAF.

Many driver mutations in cancer are specific in that they occur at significantly higher rates than - presumably - functionally alternative mutations. For example, V600E in the BRAF hydrophobic activation segment (AS) pocket accounts for >95% of all kinase mutations. While many hypotheses tried to explain such significant mutation patterns, conclusive explanations are lacking. Here, we use experimental and in silico structure-energy statistical analyses, to elucidate why the V600E mutation, but no other mutation at this, or any other positions in BRAF's hydrophobic pocket, is predominant. We find that BRAF mutation frequencies depend on the equilibrium between the destabilization of the hydrophobic pocket, the overall folding energy, the activation of the kinase and the number of bases required to change the corresponding amino acid. Using a random forest classifier, we quantitatively dissected the parameters contributing to BRAF AS cancer frequencies. These findings can be applied to genome-wide association studies and prediction models.