Adenosine increases PD-L1 expression in mesenchymal stromal cells derived from cervical cancer through its interaction with A2AR/A2BR and the production of TGF-ß1.

Mesenchymal stromal cells (MSCs) together with malignant cells present in the tumor microenvironment (TME), participate in the suppression of the antitumor immune response through the production of immunosuppressive factors, such as transforming growth factor beta 1 (TGF-ß1). In previous studies, we reported that adenosine (Ado), generated by the adenosinergic activity of cervical cancer (CeCa) cells, induces the production of TGF-ß1 by interacting with A2AR/A2BR. In the present study, we provide evidence that Ado induces the production of TGF-ß1 in MSCs derived from CeCa tumors (CeCa-MSCs) by interacting with both receptors and that TGF-ß1 acts in an autocrine manner to induce the expression of programmed death ligand 1 (PD-L1) in CeCa-MSCs, resulting in an increase in their immunosuppressive capacity on activated CD8+ T lymphocytes. The addition of the antagonists ZM241385 and MRS1754, specific for A2AR and A2BR, respectively, or SB-505124, a selective TGF-ß1 receptor inhibitor, in CeCa-MSC cultures significantly inhibited the expression of PD-L1. Compared with CeCa-MSCs, MSCs derived from normal cervical tissue (NCx-MSCs), used as a control and induced with Ado to express PD-L1, showed a lower response to TGF-ß1 to increase PD-L1 expression. Those results strongly suggest the presence of a feedback mechanism among the adenosinergic pathway, the production of TGF-ß1, and the induction of PD-L1 in CeCa-MSCs to suppress the antitumor response of CD8+ T lymphocytes. The findings of this study suggest that this pathway may have clinical importance as a therapeutic target.

Dexamethasone treatment for COVID-19 is related to increased mortality in hematologic malignancy patients: results from the EPICOVIDEHA Registry.

Not available.

Comparing outcomes in patients with exsanguinating injuries: an Eastern Association for the Surgery of Trauma (EAST), multicenter, international trial evaluating prioritization of circulation over intubation (CAB over ABC).

INTRODUCTION: Hemorrhage is a major cause of preventable trauma deaths, and the ABC approach is widely used during the primary survey. We hypothesize that prioritizing circulation over intubation (CAB) can improve outcomes in patients with exsanguinating injuries. METHODS: A prospective observational study involving international trauma centers was conducted. Patients with systolic blood pressure below 90 who were intubated within 30 min of arrival were included. Prioritizing circulation (CAB) was defined as delaying intubation until blood products were started, and/or bleeding control was performed before securing the airway. Demographics, clinical data, and outcomes were recorded. RESULTS: The study included 278 eligible patients, with 61.5% falling within the "CAB" cohort and 38.5% in the "ABC" cohort. Demographic and disease characteristics, including age, sex, ISS, use of blood products, and other relevant factors, exhibited comparable distributions between the two cohorts. The CAB group had a higher proportion of penetrating injuries and more patients receiving intubation in the operating room. Notably, patients in the CAB group demonstrated higher GCS scores, lower SBP values before intubation but higher after intubation, and a significantly lower incidence of cardiac arrest and post-intubation hypotension. Key outcomes revealed significantly lower 24-hour mortality in the CAB group (11.1% vs. 69.2%), a lower rate of renal failure, and a higher rate of ARDS. Multivariable logistic regression models showed a 91% reduction in the odds of mortality within 24 h and an 89% reduction at 30 days for the CAB cohort compared to the ABC cohort. These findings suggest that prioritizing circulation before intubation is associated with improved outcomes in patients with exsanguinating injuries. CONCLUSION: Post-intubation hypotension is observed to be correlated with worse outcomes. The consideration of prioritizing circulation over intubation in patients with exsanguinating injuries, allowing for resuscitation, or bleeding control, appears to be associated with potential improvements in survival. Emphasizing the importance of circulation and resuscitation is crucial, and this approach might offer benefits for various bleeding-related conditions.

Music Listening in Stem Cell Transplantation and Acute Myeloid Leukemia: A Randomized Clinical Trial.

CONTEXT: Music listening (ML) has been shown to have a beneficial effect on patients with cancer. However, novel intervention approaches are needed. OBJECTIVES: We aimed to determine whether ML based on the iso-principle, conducted using a mobile application (GloMus), improves symptom burden, quality of life (QoL), anxiety, and depression in patients undergoing stem cell transplantation (SCT) and intensive induction chemotherapy for acute myeloid leukemia (AML). METHODS: In this randomized controlled clinical trial, we assigned 71 patients to the ML or standard care (SC) groups, stratified by the reason for admission (AML, allogeneic-SCT, or inpatient/outpatient autologous-SCT). Upon admission, participants in the ML groups were invited to undergo daily ML sessions designed to change negative moods into positive ones (iso-principle). The intervention consisted of listening to pre-recorded classical music ordered by beats per minute and tonality. Symptom burden (Edmonton Symptom Assessment System-Revised) was assessed in the ML groups before and after each session. Anxiety, depression (Hospital Anxiety and Depression Scale), and QoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation/Leukemia) were measured weekly in the ML and SC groups. RESULTS: Symptom burden in both allogeneic- and inpatient autologous-SCT ML groups reduced after the intervention. In all experimental groups, clinically important improvements were observed after ML sessions. No differences were found between the groups (ML vs. SC) at different weeks of admission regarding anxiety, depression, and QoL. CONCLUSIONS: ML based on our innovative iso-principle strategy, conducted using GloMus, reduced the symptom burden in patients undergoing allogeneic- and inpatient autologous-SCT (ClinicalTrials.gov number, NCT05696457).

Decoding the historical tale: COVID-19 impact on haematological malignancy patients-EPICOVIDEHA insights from 2020 to 2022.

Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020-2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

Adenosine Increases the Immunosuppressive Capacity of Cervical Cancer Cells by Increasing PD-L1 Expression and TGF-ß Production through Its Interaction with A2AR/A2BR.

The present study provides evidence showing that adenosine (Ado) increases the expression of programmed death ligand 1 (PD-L1) in cervical cancer (CeCa) cells by interacting with A2AR/A2BR and that TGF-ß1 acts in an autocrine manner to induce PD-L1 expression, enhancing the immunosuppressive effects of CeCa cells on activated T lymphocytes (ATLs) and CD8+ cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from E6 and E7 proteins of HPV-16. Interestingly, the addition of the antagonists ZM241385 and MRS1754, which are specific for A2AR and A2BR, respectively, or SB-505124, which is a selective TGF-ß1 receptor inhibitor, to CeCa cell cultures significantly inhibited PD-L1 expression. In addition, supernatants from CeCa cells that were treated with Ado (CeCa-Ado Sup) increased the expression of PD-1, TGF-ß1, and IL-10 and decreased the expression of IFN-γ in ATLs. Interestingly, the addition of an anti-TGF-ß neutralizing antibody strongly reversed the effect of CeCa-Ado Sup on PD-1 expression in ATLs. These results strongly suggest the presence of a feedback mechanism that involves the adenosinergic pathway, the production of TGF-ß1, and the upregulation of PD-L1 expression in CeCa cells that suppresses the antitumor response of CTLs. The findings of this study suggest that this pathway may be clinically important and may be a therapeutic target.

Uso de la tomografía corporal total en pacientes con heridas de arma de fuego y hemodinámicamente inestables: ¿Rompiendo paradigmas de atención inicial? / Whole-body computed tomography in hemodynamically unstable patients with gunshot wounds: A paradigm shift in trauma management?

Introducción. El objetivo del estudio fue analizar el impacto del uso de la tomografía corporal total en la evaluación de los pacientes con trauma penetrante por proyectil de arma de fuego y hemodinámicamente inestables atendidos en un centro de referencia de trauma. Métodos. Se realizó un estudio analítico, retrospectivo, con base en un subanálisis del registro de la Sociedad Panamericana de Trauma ­ Fundación Valle del Lili. Se incluyeron los pacientes con trauma penetrante por proyectil de arma de fuego atendidos entre 2018 y 2021. Se excluyeron los pacientes con trauma craneoencefálico severo, trauma leve y en condición in extremis. Resultados. Doscientos pacientes cumplieron los criterios de elegibilidad, 115 fueron estudiados con tomografía corporal total y se compararon con 85 controles. La mortalidad intrahospitalaria en el grupo de tomografía fue de 4/115 (3,5 %) vs 10/85 (12 %) en el grupo control. En el análisis multivariado se identificó que la tomografía no tenía asociación significativa con la mortalidad (aOR=0,46; IC95% 0,10-1,94). El grupo de tomografía tuvo una reducción relativa del 39 % en la frecuencia de cirugías mayores, con un efecto asociado en la disminución de la necesidad de cirugía (aOR=0,47; IC95% 0,22-0,98). Conclusiones. La tomografía corporal total fue empleada en el abordaje inicial de los pacientes con trauma penetrante por proyectil de arma de fuego y hemodinámicamente inestables. Su uso no se asoció con una mayor mortalidad, pero sí con una menor frecuencia de cirugías mayores.

Introduction. This study aims to assess the impact of whole-body computed tomography (WBCT) in the evaluation of patients with penetrating gunshot wounds (GSW) who are hemodynamically unstable and treated at a trauma referral center. Methods. An analytical, retrospective study was conducted based on a subanalysis of the Panamerican Trauma Society-FVL registry. Patients with GSW treated between 2018 and 2021 were included. Patients with severe cranioencephalic trauma, minor trauma, and those in extremis were excluded. Patients with and without WBCT were compared. The primary outcome was in-hospital mortality, and the secondary outcome was the frequency of major surgeries (thoracotomy, sternotomy, cervicotomy, and/or laparotomy) during initial care. Results. Two hundred eligible patients were included, with 115 undergoing WBCT and compared to 85 controls. In-hospital mortality in the WBCT group was 4/115 (3.5%) compared to 10/85 (12%) in the control group. Multivariate analysis showed that WBCT was not significantly associated to mortality (aOR: 0.46; 95% CI 0.10-1.94). The WBCT group had a relative reduction of 39% in the frequency of major surgeries, with an associated effect on reducing the need for surgery (aOR: 0.47; 95% CI 0.22-0.98). Conclusions. Whole-body computed tomography was employed in the initial management of patients with penetrating firearm projectile injuries and hemodynamic instability. The use of WBCT was not associated with mortality but rather with a reduction in the frequency of major surgery.

Umbral crítico de administración en pacientes con trauma severo y reanimación endovascular: ¿Un concepto útil? / Critical Administration Threshold in severe trauma patients and endovascular resuscitation: A useful concept?

Introducción. Se describe la utilidad del umbral crítico de administración (CAT por su denominación en inglés) como herramienta para la reanimación hemostática en pacientes con trauma severo y oclusión endovascular aórtica. Métodos. Revisión retrospectiva de pacientes adultos con hemorragia por trauma, con o sin oclusión endovascular aórtica (REBOA), atendidos entre enero de 2015 y junio de 2020, en un centro de trauma nivel I en Cali, Colombia. Se registraron variables demográficas, severidad del trauma, estado clínico, requerimiento transfusional, tiempo hasta CAT+ y CAT alcanzado (1, 2 ó 3). Resultados. Se incluyeron 93 pacientes, se utilizó REBOA en 36 y manejo tradicional en 57. El grupo REBOA presentó mayor volumen de sangrado (mediana de 3000 ml, RIC: 1950-3625 ml) frente al grupo control (mediana de1500 ml, RIC: 700-2975ml) (p<0,001) y mayor cantidad de glóbulos rojos transfundidos en las primeras 6 horas (mediana de 5, RIC:4-9); p=0,015 y en las primeras 24 horas (mediana de 6, RIC: 4-11); p=0,005. No hubo diferencias estadísticamente significativas en número de pacientes CAT+ entre grupos o tiempo hasta alcanzarlo. Sin embargo, el estado CAT+ durante los primeros 30 minutos de la cirugía fue mayor en grupo REBOA (24/36, 66,7 %) frente al grupo control (17/57, 29,8 %; p=0,001), teniendo este mayor tasa de mortalidad intrahospitalaria frente a los pacientes CAT-. Conclusión. El umbral crítico de administración es una herramienta útil en la reanimación hemostática de pacientes con trauma y REBOA, que podría predecir mortalidad precoz.

Introduction. The objective is to describe the utility of the Critical Administration Threshold (CAT) as a tool in hemostatic resuscitation in patients with severe trauma and REBOA. Methods. Retrospective review between January 2015 and June 2020 of adult patients with hemorrhage secondary to trauma with or without REBOA in a level I trauma center in Cali, Colombia. Demographic variables, trauma severity, clinical status, transfusion needs, time to CAT+ and number of CAT achieved (1, 2 or 3) were recorded. Results. Ninety-three patients were included, in which REBOA was used in 36 and traditional management in 57. The REBOA group had a higher bleeding volume (3000 ml), IQR: 1950-3625 ml vs the control group (1500 ml, IQR: 700-2975 ml) (p<0.001) and a higher rate of PRBC units transfused in the first 6 hours (median 5, IQR: 4-9); p=0.015 and in the first 24 hours (median 6, IQR: 4-11); p=0.005. There were no statistically significant differences in the number of CAT+ patients between groups or time to CAT+. However, CAT+ status during the first 30 minutes of surgery was higher in the REBOA Group (24/36, 66.7%) vs. the control group (17/57, 29.8%; p=0.001), having this group a higher in-hospital mortality rate vs. CAT- patients. Conclusion. CAT is a useful tool in the hemostatic resuscitation of patients with trauma and REBOA that could predict early mortality.

The mortality of COVID-19 in CML patients from 2020 until 2022: results from the EPICOVIDEHA survey.

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

Vascular access complications associated with resuscitative endovascular balloon occlusion of the aorta in adult trauma patients: A systematic review and meta-analysis.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is gaining popularity worldwide for managing hypotensive trauma patients. Vascular access complications related to REBOA placement have been reported, with some cases resulting in permanent morbidity. We aim to capitalize on the increase in literature to further describe and estimate the incidence of REBOA-associated vascular access complications in adult trauma patients. METHODS: We searched Medline, EMBASE, Scopus, and CINAHL for studies reporting vascular access complications of REBOA in adult trauma patients from inception to October 14, 2021. Studies reporting data from adult trauma patients who underwent REBOA insertion were eligible. Exclusion criteria included patients 15 years and younger, nontrauma patients, non-REBOA use, non-vascular access complications and patient duplication. Study data was abstracted using the PRISMA checklist and verified independently by three reviewers. Meta-analysis of proportions was performed using a random effects model with Freeman-Turkey double-arcsine transformation. Post hoc meta-regression by year of publication, sheath-size, and geographic region was also performed. The incidence of vascular access complications from REBOA insertion was the primary outcome of interest. Subgroup analysis was performed by degree of bias, sheath size, technique of vascular access, provider specialty, geographical region, and publication year. RESULTS: Twenty-four articles were included in the systematic review and the meta-analysis, for a total of 675 trauma patients who underwent REBOA insertion. The incidence of vascular access complications was 8% (95% confidence interval, 5%-13%). In post hoc meta-regression adjusting for year of publication and geographic region, the use of a smaller (7-Fr) sheath was associated with a decreased incidence of vascular access complications (odds ratio, 0.87; 95% confidence interval, 0.75-0.99; p = 0.046; R 2 = 35%; I 2 = 48%). CONCLUSION: This study provides a benchmark for quality of care in terms of vascular access complications related to REBOA insertion in adult trauma patients. Smaller sheath size may be associated with a decrease in vascular access complications. LEVEL OF EVIDENCE: Systematic Review and Meta-Analysis; Level III.

False Positive in [ 99m Tc]Tc-DPD Scintigraphy for Cardiac Amyloidosis Due to Intravenous Iron Administration.

ABSTRACT: [ 99m Tc]Tc-DPD (3,3-diphosphono-1,2-propanodicarboxylic acid) scintigraphy is an essential tool for diagnosing transthyretin amyloid cardiac amyloidosis. An 86-year-old woman suffering from heart failure with preserved ejection fraction underwent [ 99m Tc]Tc-DPD scintigraphy and a SPECT/CT for suspected transthyretin amyloid cardiac amyloidosis. The scan showed intracardiac and liver uptake. As the patient had taken intravenous iron on the morning of the scan, we decided to repeat the scan, but this time, it showed no uptake in the heart or the liver. Accordingly, we concluded the first result was a false positive due to drug interaction.

Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry.

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109 /L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

Critical systolic blood pressure threshold for endovascular aortic occlusion-A multinational analysis to determine when to place a REBOA.

BACKGROUND: Systolic blood pressure (SBP) is a potential indicator that could guide when to use a resuscitative endovascular balloon occlusion of the aorta (REBOA) in trauma patients with life-threatening injuries. This study aims to determine the optimal SBP threshold for REBOA placement by analyzing the association between SBP pre-REBOA and 24-hour mortality in severely injured hemodynamically unstable trauma patients. METHODS: We performed a pooled analysis of the aortic balloon occlusion (ABO) trauma and AORTA registries. These databases record the details related to the use of REBOA and include data from 14 countries worldwide. We included patients who had suffered penetrating and/or blunt trauma. Patients who arrived at the hospital with a SBP pre-REBOA of 0 mm Hg and remained at 0 mm Hg after balloon inflation were excluded. We evaluated the impact that SBP pre-REBOA had on the probability of death in the first 24 hours. RESULTS: A total of 1,107 patients underwent endovascular aortic occlusion, of these, 848 met inclusion criteria. The median age was 44 years (interquartile range [IQR], 27-59 years) and 643 (76%) were male. The median injury severity score was 34 (IQR, 25-45). The median SBP pre-REBOA was 65 mm Hg (IQR, 49-88 mm Hg). Mortality at 24 hours was reported in 279 (32%) patients. Math modeling shows that predicted probabilities of the primary outcome increased steadily in SBP pre-REBOA below 100 mm Hg. Multivariable mixed-effects analysis shows that when SBP pre-REBOA was lower than 60 mm Hg, the risk of death was more than 50% (relative risk, 1.5; 95% confidence interval, 1.17-1.92; p = 0.001). DISCUSSION: In patients who do not respond to initial resuscitation, the use of REBOA in SBPs between 60 mm Hg and 80 mm Hg may be a useful tool in resuscitation efforts before further decompensation or complete cardiovascular collapse. The findings from our study are clinically important as a first step in identifying candidates for REBOA. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Functional Proteomics Characterization of the Role of SPRYD7 in Colorectal Cancer Progression and Metastasis.

SPRY domain-containing protein 7 (SPRYD7) is a barely known protein identified via spatial proteomics as being upregulated in highly metastatic-to-liver KM12SM colorectal cancer (CRC) cells in comparison to its isogenic poorly metastatic KM12C CRC cells. Here, we aimed to analyze SPRYD7's role in CRC via functional proteomics. Through immunohistochemistry, the overexpression of SPRYD7 was observed to be associated with the poor survival of CRC patients and with an aggressive and metastatic phenotype. Stable SPRYD7 overexpression was performed in KM12C and SW480 poorly metastatic CRC cells and in their isogenic highly metastatic-to-liver-KM12SM-and-to-lymph-nodes SW620 CRC cells, respectively. Upon upregulation of SPRYD7, in vitro and in vivo functional assays confirmed a key role of SPRYD7 in the invasion and migration of CRC cells and in liver homing and tumor growth. Additionally, transient siRNA SPRYD7 silencing allowed us to confirm in vitro functional results. Furthermore, SPRYD7 was observed as an inductor of angiogenesis. In addition, the dysregulated SPRYD7-associated proteome and SPRYD7 interactors were elucidated via 10-plex TMT quantitative proteins, immunoproteomics, and bioinformatics. After WB validation, the biological pathways associated with the stable overexpression of SPRYD7 were visualized. In conclusion, it was demonstrated here that SPRYD7 is a novel protein associated with CRC progression and metastasis. Thus, SPRYD7 and its interactors might be of relevance in identifying novel therapeutic targets for advanced CRC.

Comparison of Methods for Testing Mismatch Repair Status in Endometrial Cancer.

Approximately 20-30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine diagnosis. The aim of this study was to establish and compare the MMR status using various approaches. Immunohistochemistry (IHC), PCR-based MSI, and the detection of defects in the four key MMR genes (MLH1, PMS2, MSH2, and MSH6) via methylation-specific multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) were performed. MSH3 expression was also evaluated. A set of 126 early-stage EC samples were analyzed, 53.2% of which were dMMR and 46.8% of which were proficient MMR (pMMR) as determined using IHC, whereas 69.3% were classified as microsatellite stable, while 8.8% and 21.9% were classified MSI-low (MSI-L) and MSI-high (MSI-H), respectively. In total, 44.3% of the samples showed genetic or epigenetic alterations in one or more genes; MLH1 promoter methylation was the most common event. Although acceptable concordance was observed, there were overall discrepancies between the three testing approaches, mainly associated with the dMMR group. IHC had a better correlation with MMR genomic status than the MSI status determined using PCR. Further studies are needed to establish solid conclusions regarding the best MMR assessment technique for EC.

Spontaneous Pneumomediastinum in Marijuana Users.

This article presents two individuals with different clinical presentations who experienced spontaneous pneumomediastinum following the chronic use of marijuana. Pneumomediastinum has been associated with marijuana use due to the prolonged inhalation and breath-holding mechanisms employed during consumption. The first case involves a 24-year-old woman with a history of anxiety and chronic marijuana use, who presented to the emergency department with atypical chest pain and shortness of breath. The second case involves a 21-year-old man with no previous medical history, who experienced acute chest pain after smoking marijuana. Both individuals exhibited signs of pneumomediastinum on imaging studies and were treated with oxygen therapy and analgesics. The cases emphasize the importance of considering pneumomediastinum in patients with atypical chest pain, particularly in chronic cannabis users.

Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings.

OBJECTIVES: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. METHODS: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. RESULTS: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. CONCLUSION: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Frailty assessment to individualize treatment in older patients with lymphoma.

PURPOSE: A study analyzing the application of a protocol of comprehensive geriatric assessment (CGA) in older patients with lymphoma was carried out to allow frailty-based patient classification and individualized treatment. METHODS: Lymphoma patients older than 70 years referred to the Geriatric Clinic at a tertiary hospital between May 2016 and March 2021 were included. The assessment protocol included comorbidity, polypharmacy, nutritional, functional, and mental status, geriatric syndromes, and life expectancy. CGA enabled patient classification into four groups (Type I to Type IV) based on frailty assessment instrument scoring and clinical, functional, and mental status. Variables were compared using parametric and non-parametric statistical tests and Kaplan-Meier survival curves. RESULTS: Ninety-three patients (55.9% women) were included. Median age was 81.1 years (± 5.7). 23 patients (24.7%) were classified as robust (type I), 30 (32.3%) as pre-frail (type II) with potentially reversable deficits, 38 (40.9%) as frail (type III), and 2 (2.2%) as requiring palliative care (type IV). Patients received oncospecific treatment with modifications carried out in 64.5% of cases based on CGA results. Differences in overall survival (p = 0.002), response to treatment (p < 0.001) and likelihood of increased frailty (p = 0.024) were observed, with type III-IV patients showing significantly worse outcomes. CONCLUSION: Performance of standardized, systematic CGA by geriatricians permits older lymphoma patients to be classified according to frailty, with significant differences in terms of clinical outcomes across groups. We propose incorporating CGA performed by geriatricians as part of the multidisciplinary care team to optimize therapeutic strategy for these patients.

Clinical and Radiological Outcomes of Computer-Assisted versus Conventional Total Knee Arthroplasty at 5-Year Follow-Up: Is There Any Benefit?

Computer-assisted total knee arthroplasty (CAS) remains controversial. Some authors defend that its improvement in knee alignment and positioning positively impacts arthroplasty survival rates, while others have stated that there is minimal or no difference compared to the conventional technique (cTKA). This paper features a retrospective, single-center, single-surgeon study, evaluating CAS surgery vs. regular cTKA in patients who consecutively underwent surgery between 2015 and 2017 (60 CAS patients vs. 59 cTKA). Data collection includes surgery duration, length of stay, blood loss and both preoperative and postoperative clinical outcome evaluation using WOMAC, SF-12, Forgotten Joint Score and VAS. Radiograph evaluation includes the tibiofemoral angle, posterior condylar offset and its ratio, and notching frequency and measurement. A total of 119 patients were included: 60 in the CAS group and 59 in the cTKA. Mean follow-up was 5.61 years (Max 7.83-Min 5.02 years). No clinically relevant preoperative differences were observed between the groups. Postoperatively, both groups showed similar functional results (WOMAC, SF-12, FJS, KSS, and VAS) with similar complication rates. The CAS group had an increased surgery time by a mean of 12 min (107.02 ± 15.22 vs. 95.32 + 13.87; p = 0.00) as well as a higher notching frequency and size (40% vs. 13.60%; p = 0.013; 1.239 mm ± 1.7604 vs. 0.501 mm ± 1.4179; p = 0.031). CAS obtained similar functional, radiological, and complication rates to cTKA at the expense of increasing surgery time and notching frequency and size.

Non-timely referral of women aged 40 to 69 to preventive medicine for breast cancer detection and its association with the BI-RADS classification.

Purpose: In the first level of health care, the timely detection of breast cancer is essential to prevent the progression of the disease, obtain optimal treatment and improve the prognosis and survival of patients. The objective of this study was to analyze the opportunity in referral to the Preventive Medicine Modules offered to women aged 40 to 69 years of the Family Medicine Unit 1, of the Mexican Social Security Institute, Decentralized Administrative Operation Body, Aguascalientes, Mexico, by their family physician, and its impact in the findings of mammographic screening according to the BI-RADS classification. Methods This was a cross-sectional comparative study of 412 mammograms performed on women aged 40 to 69, who were treated in the preventive medicine modules from January 2019 to June 2021. Data collection was carried out by simple random sampling using a checklist. Multiple logistic regression models adjusted for age were applied. Results: A total of 90.29% of the patients who underwent screening mammography were not referred in a timely manner to the preventive medicine modules by the family physician, this delay in diagnosis and treatment increased by 3.01 times the probability of having a classification BI-RADS suspected of malignancy compared to those women whose referral was timely (OR adj = 3.01, 95% CI 1.04-8.72, p = 0.041). Conclusion: The untimely referral of women aged 40-69 to preventive medicine modules for the detection of breast cancer increases the risk of finding a malignant lesión.