The use of procedural kits may reduce unscheduled central line dressing changes: A matched pre-post intervention study.

Background: Unscheduled dressing changes for central venous lines (CVLs) have been shown to increase the risk of bloodstream infections. Objective: The objective of this study is to determine if the use of an innovative dressing change kit reduces the rate of unscheduled dressing changes. Methods: This pre-post interventional study took place at a large, academic, tertiary care center in metro Detroit, Michigan, the United States. We assessed the impact of the interventional dressing change procedure kit on the rate of unscheduled dressing changes for adult patients who underwent placement of a CVL inclusive of a central catheter, peripherally inserted central catheter, or hemodialysis catheter. Data was collected for the pre-intervention cohort through electronic health records (EHRs), while data for the post-intervention cohort were collected by direct observation by trained research staff in combination with EHR data. The primary outcome was the rate of unscheduled dressing changes. Secondary outcomes included rate of unscheduled dressing changes based on admission floor type, etiology of unscheduled dressing changes, and central line-associated bloodstream infections (CLABSIs). Results: The study included a convenience sample of 1548 CVLs placed between May 2018 and June 2022 with a matched analysis including 488 catheters in each of the pre- and post-intervention groups. The results showed that the unadjusted rate of unscheduled dressing evaluations was significantly reduced from the pre-intervention group (0.21 per day) to the post-intervention group (0.13 per day) (p < .001). The adjusted rate ratio demonstrated the same trend at 1.00 pre- and 0.60 post-intervention (p < .001). Stratifying the analysis based on the highest level of care showed that the intervention was effective in reducing the unadjusted rate of unscheduled dressing evaluations for both the advanced and regular medical floor subgroups pre- to post-intervention; the advanced subgroup had an reduction from 0.22 to 0.15 per day (p = .001), while the regular medical floor subgroup had a reduction from 0.21 to 0.09 per day (p < .001). CLABSIs were similar in both groups (0.6% vs 0.8%; p = 1.00) in pre- and post-intervention groups, respectively. Discussion: Procedural kits for central line dressing changes are effective in reducing unscheduled dressing changes and may have a role in reducing CLABSI. Further studies assessing the impact of dressing change kits on cost, procedural compliance, and the precise impact on CLABSI are needed.

Germline homozygosity and allelic imbalance of HLA-I are common in esophagogastric adenocarcinoma and impair the repertoire of immunogenic peptides.

BACKGROUND: The individual HLA-I genotype is associated with cancer, autoimmune diseases and infections. This study elucidates the role of germline homozygosity or allelic imbalance of HLA-I loci in esophago-gastric adenocarcinoma (EGA) and determines the resulting repertoires of potentially immunogenic peptides. METHODS: HLA genotypes and sequences of either (1) 10 relevant tumor-associated antigens (TAAs) or (2) patient-specific mutation-associated neoantigens (MANAs) were used to predict good-affinity binders using an in silico approach for MHC-binding (www.iedb.org). Imbalanced or lost expression of HLA-I-A/B/C alleles was analyzed by transcriptome sequencing. FluoroSpot assays and TCR sequencing were used to determine peptide-specific T-cell responses. RESULTS: We show that germline homozygosity of HLA-I genes is significantly enriched in EGA patients (n=80) compared with an HLA-matched reference cohort (n=7605). Whereas the overall mutational burden is similar, the repertoire of potentially immunogenic peptides derived from TAAs and MANAs was lower in homozygous patients. Promiscuity of peptides binding to different HLA-I molecules was low for most TAAs and MANAs and in silico modeling of the homozygous to a heterozygous HLA genotype revealed normalized peptide repertoires. Transcriptome sequencing showed imbalanced expression of HLA-I alleles in 75% of heterozygous patients. Out of these, 33% showed complete loss of heterozygosity, whereas 66% had altered expression of only one or two HLA-I molecules. In a FluoroSpot assay, we determined that peptide-specific T-cell responses against NY-ESO-1 are derived from multiple peptides, which often exclusively bind only one HLA-I allele. CONCLUSION: The high frequency of germline homozygosity in EGA patients suggests reduced cancer immunosurveillance leading to an increased cancer risk. Therapeutic targeting of allelic imbalance of HLA-I molecules should be considered in EGA.

Evolutionary trajectories of small cell lung cancer under therapy.

The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown1-3. Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity. We observed branched evolution and a shift to ancestral clones underlying tumour relapse. Effective radio- or immunotherapy induced a re-expansion of founder clones with acquired genomic damage from first-line chemotherapy. Whereas TP53 and RB1 alterations were exclusively part of the common ancestor, MYC family amplifications were frequently not constituents of the founder clone. At relapse, emerging subclonal mutations affected key genes associated with SCLC biology, and tumours harbouring clonal CREBBP/EP300 alterations underwent genome duplications. Gene-damaging TP53 alterations and co-alterations of TP53 missense mutations with TP73, CREBBP/EP300 or FMN2 were significantly associated with shorter disease relapse following chemotherapy. In summary, we uncover key processes of the genomic evolution of SCLC under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with sensitivity and resistance to chemotherapy.

Diagnostic Performance of Diastolic Hyperemia-Free Ratio Compared With Invasive Fractional Flow Reserve for Evaluation of Coronary Artery Disease.

Hyperemic and nonhyperemic pressure ratios are frequently used to assess the hemodynamic significance of coronary artery disease and to guide the need for myocardial revascularization. However, there are limited data on the diagnostic performance of the diastolic hyperemia-free ratio (DFR). We evaluated the diagnostic performance of the DFR compared with invasive fractional flow reserve (FFR). We performed a prospective, single-center study of 308 patients (343 lesions) who underwent DFR and FFR for evaluation of visually estimated 40% to 90% stenoses. Diagnostic performance of the DFR compared with FFR was evaluated using linear regression, Bland-Altman analysis, and receiver operating characteristic curves. The overall diagnostic accuracy of the DFR was 83%; the accuracy rates were 86%, 40%, and 95% when the DFR was <0.86, 0.88 to 0.90, and >0.93, respectively. The sensitivity, specificity, positive predicative value, and negative predictive value were 60%, 91%, 71%, and 87%, respectively. The Pearson correlation coefficient was 0.75 (p <0.05). The Bland-Altman analysis showed a mean difference of 0.09, and the area under the receiver operating characteristic curve was 0.88 (95% confidence interval 0.84 to 0.92, p <0.05). In conclusion, the DFR has a good diagnostic performance compared with FFR but 17% of the measurements were discordant. The diagnostic accuracy of the DFR was only 40% when the DFR was 0.88 to 0.90, suggesting that FFR may be useful in these arteries.

Clinical and physical efficiency of virtual reality games in soccer players with low back pain / Eficiencia de los juegos de realidad virtual en jugadores de futbol con dolor de espalda baja / Eficiência clínica e física de jogos de realidade virtual em jogadores de futebol com dor lombar

ABSTRACT Introduction: Virtual reality training (VRT) is an advanced technology that creates virtual games by a computer through specific software. It is a type of rehabilitation training commonly used in balance problems to treat musculoskeletal conditions. Objective: To determine and compare the effects of virtual reality games with those of core stabilization training on physical efficiency in soccer players with chronic low back pain. Methods: A randomized, double-blinded, controlled study was conducted on 60 LBP participants at a university hospital. The first group (n=20) received virtual reality (VR) training; the second group (n=20) received core stabilization (CS) training; and the third group (n=20) received conventional training exercises for four weeks. Scores of clinical and sports performance were measured at baseline, and after 4 weeks, 8 weeks and 6 months. Results: The baseline demographic and clinical characters did not show any significant differences (p>0.05) in the statistical analysis, which shows a homogenous population. Four weeks following the training, the VR training group showed more significant changes in clinical scores than the CS training and control groups (p≤0.001). The scores for sports performance also showed more significant improvement in the VR training group than in the other two groups (p≤0.001). The same improved clinical and sports performance changes were seen at 8 weeks and 6 months of follow-up in the VR training group, when compared to the other two groups (p≤0.001). Conclusion: This study suggests that training through virtual reality games results in long-term improvement in clinical and sports performance compared to other forms of training in soccer players with chronic low back pain.Level of evidence I b; Therapeutic studies - Investigation of treatment results.

RESUMEN Introducción: El entrenamiento de realidad virtual (VRT) es una tecnología avanzada, que crea juegos virtuales por computadora a través de un software específico. Es un tipo de entrenamiento de rehabilitación que se usa comúnmente en problemas de equilibrio para tratar afecciones musculoesqueléticas. Objetivo: Encontrar y comparar los efectos de los juegos de realidad virtual sobre el entrenamiento de estabilización central sobre la eficiencia física en jugadores de fútbol con dolor lumbar crónico. Métodos: Se realizó un estudio controlado, aleatorizado, doble ciego en 60 participantes con dolor lumbar en un hospital universitario. El primer grupo (n = 20) recibió entrenamiento de realidad virtual (VR), el segundo grupo (n = 20) recibió entrenamiento de estabilización central (CS) y el tercer grupo (n = 20) recibió ejercicios de entrenamiento convencionales durante cuatro semanas. Los puntajes de rendimiento clínico y deportivo se midieron al inicio del estudio, después de 4 semanas, 8 semanas y 6 meses. Resultados: Los caracteres demográficos y clínicos basales no mostraron ninguna diferencia significativa (p. 0,05) en el análisis estadístico lo que indica una población homogénea. Cuatro semanas después del entrenamiento, el grupo de entrenamiento de RV mostró cambios más significativos en las puntuaciones clínicas que los de entrenamiento de CS y los grupos de control (p≤0,001). Las puntuaciones de rendimiento deportivo también mostraron una mejora significativa en el grupo de entrenamiento de RV comparadas con los otros dos grupos (p≤0,001). Hubo los mismos cambios clínicos y de rendimiento deportivo a las 8 semanas y 6 meses de seguimiento en el grupo de entrenamiento de RV y en los otros dos grupos (p≤0,001). Conclusión: Nuestro estudio sugirió que el entrenamiento a través de juegos de realidad virtual mejoró el rendimiento clínico y deportivo más que otros entrenamientos en jugadores de fútbol con dolor lumbar crónico a largo plazo. Nivel de evidencia Ib; Estudios terapéuticos, investigación de los resultados del tratamiento.

RESUMO Introdução: O treinamento com realidade virtual (TRV) é uma tecnologia avançada que cria jogos virtuais para computador por meio de software específico. É um tipo de treinamento de reabilitação comumente usado em problemas de equilíbrio no tratamento de doenças musculoesqueléticas. Objetivo: Determinar e comparar os efeitos dos jogos de realidade virtual com o treinamento de estabilização central na eficiência física de jogadores de futebol com dor lombar crônica. Métodos: Estudo randomizado, duplo-cego e controlado realizado com 60 participantes com lombalgia em um hospital universitário. O primeiro grupo (n = 20) recebeu treinamento de realidade virtual (RV), o segundo grupo (n = 20) recebeu treinamento de estabilização central (EC) e o terceiro grupo (n = 20) recebeu exercícios de treinamento convencional por quatro semanas. Os escores de desempenho clínico e esportivo foram medidos no início do estudo e depois de 4 semanas, 8 semanas e 6 meses. Resultados: As características demográficas e clínicas basais não mostraram diferença significativa (p > 0,05) na análise estatística, o que indica população homogênea. Quatro semanas depois do treinamento, o grupo RV mostrou mudanças mais significativas nos escores clínicos do que os grupos EC e controle (p ≤ 0,001). Os escores de desempenho esportivo também mostraram melhora significativa no grupo RV do que nos outros dois grupos (p ≤ 0,001). As mesmas mudanças benéficas de desempenho clínico e esportivo foram observadas em 8 semanas e 6 meses de acompanhamento no grupo RV em comparação com os outros dois grupos (p ≤ 0,001). Conclusão: Este estudo sugere que o treinamento com jogos de realidade virtual resulta em melhora do desempenho clínico e esportivo a longo prazo do que outras formas de treinamento em jogadores de futebol com dor lombar crônica. Nível de evidência Ib; Estudos terapêuticos, Investigação dos resultados de tratamentos.